Age-adjusted D-dimer cutoff for the diagnosis of pulmonary embolism: A cost-effectiveness analysis.
Blondon Marc,Le Gal Gregoire,Meyer Guy,Righini Marc,Robert-Ebadi Helia
Journal of thrombosis and haemostasis : JTH
BACKGROUND:In patients with suspected pulmonary embolism (PE) and a non-high pretest probability, the use of an age-adjusted D-dimer cutoff (AADD, <500 ng/mL up to 50 years, then <age × 10 ng/mL) was shown to further reduce the need for computed tomography pulmonary angiography while safely ruling out PE. Our objective was to evaluate its cost-effectiveness. METHODS:We created a decision tree to compare the use of the AADD with the standard D-dimer cutoff. The model included short-term venous thromboembolism-related events and long-term complications, their associated morbidity/mortality, and costs. Probabilities were derived from published literature and the ADJUST-PE study, and costs from US estimates. The time horizon was lifetime, with a health care system perspective. RESULTS:Using the AADD cutoff, compared with the standard cutoff, was associated with a loss of 0.0001 quality-adjusted life-years (QALY) and an average cost reduction of $33.4. The decremental cost-effectiveness ratio (DCER) was +$282 881/lost QALY (95% confidence interval from +$43 209/lost QALY to a dominant strategy). The probability that the use of the AADD cutoff was either dominant or gained >$200 000/lost QALY was 79.4%. In sensitivity analyses, the DCER became <+$200 000/lost QALY only if, among patients with D-dimer below the AADD cutoff, the mortality of an undiagnosed PE was >6% or the prevalence of PE was >0.6%. CONCLUSIONS:The AADD cutoff results in a clinically nonsignificant decrease in QALY but important costs reductions. It is a decrementally cost-effective innovation, with a potential of cost savings of >$80 million per year for the United States health care system.
Prognostic significance of preoperative plasma D-dimer level in patients with surgically resected clinical stage I non-small cell lung cancer: a retrospective cohort study.
Kaseda Kaoru,Asakura Keisuke,Kazama Akio,Ozawa Yukihiko
Journal of cardiothoracic surgery
BACKGROUND:Plasma D-dimer level, a marker of hypercoagulation, has been reported to be associated with survival in several types of cancers. The present study aimed to evaluate the prognostic significance of preoperative D-dimer levels in patients with surgically resected clinical stage I non-small cell lung cancer (NSCLC). METHODS:Participants comprised 237 patients with surgically resected clinical stage I NSCLC. In addition to factors such as age, sex, and smoking status, the association between preoperative D-dimer level and survival was explored. RESULTS:Patients were divided into two groups according to D-dimer level: Group A, ≤ 1.0 μg/ml (n = 170); and Group B, > 1.0 μg/ml (n = 67). The 5-year recurrence-free survival rate was 81.6% for Group A and 66.6% for Group B (p < 0.001). The 5-year overall survival rate was 93.6% for Group A and 84.7% for Group B (p = 0.002). Multivariate survival analysis identified D-dimer level as an independent prognostic factor, along with age, maximum standardized uptake value of the primary tumor, and pathological stage. CONCLUSIONS:Preoperative D-dimer level is an independent prognostic factor in patients with surgically resected clinical stage I NSCLC.
Age-adjusted D-dimer thresholds in the investigation of suspected pulmonary embolism: A retrospective evaluation in patients ages 50 and older using administrative data.
Senior Kevin,Burles Kristin,Wang Dongmei,Grigat Daniel,Innes Grant D,Andruchow James E,Lang Eddy S,McRae Andrew D
OBJECTIVES:D-dimer testing is an important component of the workup for pulmonary embolism (PE). However, age-related increases in D-dimer concentrations result in false positives in older adults, leading to potentially unnecessary imaging utilization. The objective of this study was to quantify the test characteristics of an age-adjusted D-dimer cut-off for ruling out PE in older patients investigated in actual clinical practice. METHODS:This observational study used administrative data from four emergency departments from July 2013 to January 2015. Eligible patients were ages 50 and older with symptoms of PE who underwent D-dimer testing. The primary outcome was 30-day diagnosis of PE, confirmed by imaging reports. Test characteristics of the D-dimer assay were calculated using the standard reference value (500 ng/ml), the local reference value (470 ng/ml), and an age-adjusted threshold (10 ng/ml × patient’s age). RESULTS:This cohort includes 6,655 patients ages 50 and older undergoing D-dimer testing for a possible PE. Of these, 246 (3.7%) were diagnosed with PE. Age-adjusted D-dimer cut-offs were more specific than standard cut-offs (75.4% v. 63.8%) but less sensitive (90.3% v. 97.2%). The false-negative risk in this population was 0.49% using age-adjusted D-dimer cut-offs compared with 0.15% with traditional cut-offs. CONCLUSION:Age-adjusted D-dimer cut-offs are substantially more specific than traditional cut-offs and may reduce CT utilization among older patients with suspected PE. We observed a loss of sensitivity, with an increased risk of false-negatives, using age-adjusted cut-offs. We encourage further evaluation of the safety and accuracy of age-adjusted D-dimer cut-offs in actual clinical practice.
[Analysis of D-dimer laboratory findings and clinical evaluation].
D-dimer is a product of the enzymatic degradation of the fibrinogen-fibrin molecule, and its existence is demonstrable in circulation. The test based limits may be considered as normal values. It was first thought to be a product of coagulation, then a product of lysis. High-concentration D-dimer in blood detected in thromboembolic diseases is considered to be of diagnostic value. In cases where thromboembolism was ruled out despite elevated titres but heparin (LMWH) or CLOPIDOGREL was given as a cautionary measure, we found that D-dimer values remained elevated. This finding means that in vivo coagulation is not a precondition to D-dimer formation. Analysis of such cases uncovers liver or kidney disease in the background, but old age may also be a factor. Often elevated ferritin levels were observed 'in parallel' with elevated D-dimer values. These findings lead us to presume an enzymatic degradation process of 'elderly' protein molecules, which is universally applicable. Orv Hetil. 2017; 158(50): 1971-1976.
Biomarkers for the diagnosis of venous thromboembolism: D-dimer, thrombin generation, procoagulant phospholipid and soluble P-selectin.
Riva Nicoletta,Vella Kevin,Hickey Kieron,Bertù Lorenza,Zammit Daniel,Spiteri Silvana,Kitchen Steve,Makris Michael,Ageno Walter,Gatt Alex
Journal of clinical pathology
BACKGROUND:The diagnostic algorithm for venous thromboembolism (VTE) currently involves a composite of pre-test probability, D-dimer and imaging. Other laboratory tests, however, may assist in the identification of patients with VTE. AIM:To assess the accuracy of different coagulation tests (D-dimer, thrombin generation, phospholipid-dependent (PPL) clotting time, soluble P-selectin (sP-selectin)) as biomarkers of acute VTE. METHODS:Random samples arriving at the Coagulation Laboratory at Mater Dei Hospital (Msida, Malta) from the Accident and Emergency Department with a request for D-dimer measurement were collected between August 2015 and February 2016. The following tests were performed: Innovance D-dimer (Siemens Healthcare Diagnostics), HemosIL D-dimer HS (Instrumentation Laboratory), thrombin generation (using the calibrated automated thrombogram), STA Procoag PPL (Diagnostica Stago) and sP-selectin (Affymetrix; eBioscience). VTE was objectively confirmed by compression ultrasonography, CT pulmonary angiography or ventilation/perfusion lung scan. RESULTS:100 samples were collected (33 with VTE). A strong positive linear correlation was found between the two D-dimer tests (r=0.97, p<0.001). Patients with VTE showed significantly higher sP-selectin concentrations compared with patients without VTE (75.7 ng/mL vs 53.0 ng/mL, p<0.001). In the random forest plot, the two D-dimer assays showed the highest variable importance, followed by sP-selectin. A sP-selectin cut-off of 74.8 ng/mL was associated with 72.7% sensitivity and 78.2% specificity for acute VTE in our cohort. CONCLUSION:Our results confirmed D-dimer as the main biomarker of VTE and speculated a role for sP-selectin. The impact of thrombin generation was limited and no role emerged for the PPL clotting time. These observations need to be confirmed in large management studies.
D-dimer as a potential blood biomarker for disease activity and treatment response in chronic urticaria: a focused review.
Ghazanfar Misbah Noshela,Thomsen Simon Francis
European journal of dermatology : EJD
Chronic urticaria is an itchy skin disease, which is treated with antihistamines; however, a large group of patients are unresponsive to antihistamines alone and are thus treated with omalizumab, although a small fraction of these patients have particularly recalcitrant disease. Currently, there are no reliable biomarkers available to assess disease activity/severity and treatment response in chronic urticaria patients. However, it has been reported that high levels of D-dimer are observed during disease activity and are significantly reduced during periods of remission. We present a focused overview of studies investigating plasma D-dimer level as a biomarker for disease activity and treatment response in patients with chronic urticaria.
Diagnostic utility of an age-specific cut-off for d-dimer for pulmonary embolism assessment when used with various pulmonary embolism risk scores.
Ackerly Imogen,Klim Sharon,McFarlane James,Kelly Anne-Maree
Internal medicine journal
This retrospective cohort study compared the diagnostic utility (sensitivity, specificity and negative predictive value (NPV)) of the age-times-10 adjusted d-dimer cut-off used in combination with the original and simplified Well's pulmonary embolism (PE) scores and the original and simplified revised Geneva scores to identify patients in whom PE is classified as unlikely according to each score. The PE risk scores performed similarly with high sensitivity (97.6, 97.1, 96.9 and 97.1% respectively) and NPV (99.3, 99.3, 99.2 and 99.2% respectively). Each missed only one PE. The age-times-10 age-adjusted d-dimer assay cut-off performed similarly with each of the clinical risk scores tested with high sensitivity and NPV.
Diagnostic accuracy of biomarker D-dimer in patients after stroke suspected from venous thromboembolism: A diagnostic meta-analysis.
Zhang Dongdong,Li Fenfen,Du Xiaowei,Zhang Xiaoyan,Zhang Zaihang,Zhao Wanyu,Du Ganqin
D-dimer is a promising biomarker for identification of venous thromboembolism (VTE) in patients with stroke. The purpose of our study is to evaluate the diagnostic value of D-dimer as a promising biomarker for VTE in patients after stroke. We performed an exhaustive search of leading databases including Pubmed, Embase, the Cochrane library, China National Knowledge Infrastructure (CNKI), and China Biology Medicine disc (CBM) from inception to Oct 13, 2017. We included studies written in English and Chinese. We included studies that appraised the diagnostic value of D-dimer with reference standard for VTE diagnosis in patients after stroke. We concurrently constructed a 2 × 2 table with data extracted from included studies. We identified 8 studies that included 1490 patients after stroke from our database searches. The pooled result from limited evidence showed a sensitivity of 0.85 (95% CI 0.76-0.90) and a specificity of 0.77 (95% CI 0.73-0.81). The area under the summary receiver operating characteristic curve was 0.85(95% CI 0.81-0.88). The positive likelihood ratio (LR+) and the negative likelihood ratio (LR-) were 3.8 (95% CI 3.1-4.4) and 0.20(95% CI 0.12-0.31), respectively. In patients after stroke suspected of venous thromboembolism, D-dimer is a beneficial biomarker for diagnosis of VTE. For stroke patients with low probability of VTE, a normal D-dimer test can be used to rule-out VTE. However, we do not recommend using D-dimer as the single definitive test for VTE diagnosis. We recommend diagnosing VTE using multi-branch diagnostic strategy.
Postoperative D-dimer predicts venous thromboembolism in patients undergoing urologic tumor surgery.
Shi An,Huang Jiwei,Wang Xun,Li Mingyang,Zhang Jin,Chen Yonghui,Huang Yiran
PURPOSE:We examined the incidence of pulmonary thromboembolism (PE) and deep venous thromboembolism (DVT) in patients who underwent urologic tumor surgery. The aim of this study was to investigate the postoperative D-dimer for prediction of venous thromboembolism events (VTE), as well as to identify other risk factors associated with the occurrence of thromboembolisms. PATIENTS AND METHODS:This was a prospective observational cohort study, which included 1,269 patients who underwent major urologic tumor surgery, from August 2015 to February 2017, at our center. Data comprising age, sex, body mass index, Charlson comorbidity index, type of surgery, Caprini score, postoperative D-dimer levels, and other laboratory tests were collected for analyses. Lower limb venous ultrasound was performed before surgery and the day before hospital discharge to measure DVT. Computerized tomography or ventilation/perfusion lung scan was applied to detect PE. RESULTS:The overall incidence of VTE was 2.4% (31 cases) in 1,269 patients, consisting of 23 PE events and 9 DVT events. Patients undergoing radical cystectomy were most likely to suffer VTE (4.3%). The optimal cutoff value for postoperative D-dimer was 0.98μg/ml, according to the receiver operating characteristic curve analysis, with a sensitivity of 83.9%, and a specificity of 80.0%. On multivariate analysis, hypertension (odds ratio, OR = 2.5, 95% CI: 1.1-5.7; P = 0.026), Charlson comorbidity index ≥ 2 (OR = 5.6, 95% CI: 2.2-14.6; P<0.001), and D-dimer lever ≥ 1μg/ml on postoperative day 1 (OR = 12.52, 95% CI: 4.6-35.2; P<0.001) were independently associated with VTE after urologic tumor surgery. CONCLUSIONS:The overall incidence of urologic-tumor-surgery-associated VTE in an Asian population is similar to those reported in European and North American series. Elevated D-dimer early after operation is an independent predictor of VTE in patients undergoing urologic tumor surgery. In addition, hypertension and the Charlson comorbidity index are both important clinical risk factors. The Caprini score recommended by the guideline is inadequate in this study population. The postoperative D-dimer plasma level is a more reliable marker for identifying patients at high-risk of developing venous thromboembolisms.
International, multicenter evaluation of a new D-dimer assay for the exclusion of venous thromboembolism using standard and age-adjusted cut-offs.
Parry Blair Alden,Chang Anna Marie,Schellong Sebastian M,House Stacey L,Fermann Gregory J,Deadmon Erin K,Giordano Nicholas J,Chang Yuchiao,Cohen Jason,Robak Nancy,Singer Adam J,Mulrow Mary,Reibling Ellen T,Francis Samuel,Griffin S Michelle,Prochaska Jürgen H,Davis Barbara,McNelis Patricia,Delgado Joao,Kümpers Philipp,Werner Nikos,Gentile Nina T,Zeserson Eli,Wild Philipp S,Limkakeng Alexander T,Walters Elizabeth Lea,LoVecchio Frank,Theodoro Daniel,Hollander Judd E,Kabrhel Christopher
INTRODUCTION:We sought to determine the test characteristics of an automated INNOVANCE D-dimer assay for the exclusion of pulmonary embolism (PE) and deep venous thrombosis (DVT) in emergency department (ED) patients using standard and age-adjusted cut-offs. METHODS:Cross-sectional, international, multicenter study of consecutive patients with suspected DVT or PE in 24 centers (18 USA, 6 Europe). Evaluated patients had low or intermediate Wells PE or DVT scores. For the standard cut-off, a D-dimer result <500 ng/ml was negative. For the age adjusted cut-off, we used the formula: Age (years) ∗ 10. The diagnostic standard was imaging demonstrating PE or DVT within 3 months. We calculated test characteristics using standard methods. We also explored modifications of the age adjustment multiplier. RESULTS:We included 3837 patients and excluded 251. The mean age of patients evaluated for PE (n = 1834) was 48 ± 16 years, with 676 (37%) male, and 1081 (59%) white. The mean age of evaluated for DVT (n = 1752) was 53 ± 16 years, with 710 (41%) male, and 1172 (67%) white. D-dimer test characteristics for PE were: sensitivity 98.0%, specificity 55.4%, negative predictive value (NPV) 99.8%, positive predictive value (PPV) 11.4%, and for DVT were: sensitivity 92.0%, specificity 44.8%, NPV 98.8%, PPV 10.3%. Age adjustment increased specificity (59.6% [PE], 51.1% [DVT]), but increasing the age-adjustment multiplier decreased sensitivity without increasing specificity. CONCLUSIONS:INNOVANCE D-dimer is highly sensitive and can exclude PE and DVT in ED patients with low- and intermediate- pre-test probability. Age-adjustment increases specificity, without increasing false negatives.
Age-adjusted versus clinical probability-adjusted D-dimer to exclude pulmonary embolism.
Takach Lapner Sarah,Stevens Scott M,Woller Scott C,Snow Gregory,Kearon Clive
INTRODUCTION:A low D-dimer can exclude suspected pulmonary embolism (PE) in cases with low or intermediate clinical probability of disease. Yet D-dimer is nonspecific, so many cases without PE require imaging. D-dimer's specificity is improved by increasing the threshold for a positive test with age (age × 10 ng/mL; age-adjusted D-dimer; AADD) or clinical probability of PE (1000 ng/mL if low and 500 ng/mL if intermediate clinical probability; clinical probability-adjusted D-dimer; CPADD). It is unclear which approach is preferable. OBJECTIVES:We report the sensitivity, specificity and negative predictive value (NPV) of AADD compared to CPADD in suspected PE. MATERIALS AND METHODS:A retrospective cohort of 3500 consecutive cases imaged for suspected PE at two U.S. emergency departments was assembled. We analyzed cases with low or intermediate clinical probability of PE (Revised Geneva Score) who had a D-dimer. The outcome was acute PE on imaging at presentation. RESULTS:Of the 3500 cases, 1745 were eligible. 37% were low, and 63% were intermediate clinical probability of PE. PE was present in 145 (8.3%) cases. Sensitivity of CPADD was 87.5% vs. 96.6% for AADD (difference 9.1%; 95% CI 4.3% to 14.0%). NPV of CPADD was 97.1% vs. 99.0% for AADD (difference 1.9%; 95% CI, 0.7% to 3.1%). Specificity of CPADD was 37.5% vs. 30.2% for AADD (difference -7.3%; 95% CI -9.4% to -5.1%). D-dimer was negative in 35.4% of cases using CPADD vs. 28.0% using AADD. CONCLUSIONS:CPADD modestly improved the specificity of D-dimer, but had a lower NPV than AADD. AADD appears preferable in this analysis.
Characteristics and Treatment Outcomes of Acute Type A Aortic Dissection With Elevated D-Dimer Concentration.
Itagaki Ryo,Kimura Naoyuki,Mieno Makiko,Hori Daijiro,Itoh Satoshi,Akiyoshi Kei,Yuri Koichi,Tanno Keisuke,Kawahito Koji,Yamaguchi Atsushi
Journal of the American Heart Association
BACKGROUND:Clinical characteristics and treatment outcomes of acute type A aortic dissection with D-dimer elevation have not been clarified. METHODS AND RESULTS:D-dimer was measured preoperatively within 24 hours of symptom onset in 262 patients with acute type A aortic dissection. The median (and interquartile range) admission D-dimer concentration in our total patient group was 26.7 (8.3-85.9) μg/mL. Median (interquartile range) D-dimer concentrations were 5.0 (2.6-18.0) μg/mL for complete false lumen thrombosis (n=33), 60.9 (19.4-160.4) μg/mL for partial thrombosis (n=81), 26.5 (10.0-70.6) μg/mL for a patent false lumen (n=131), and 8.7 (3.2-26.9) μg/mL for ulcerlike projection (n=17) (0.01). With a D-dimer concentration of ≤8.3 μg/mL representing the lower quartile, we then investigated predictors of a low D-dimer level. Multivariate analysis showed dissection limited to the ascending aorta (0.01; odds ratio, 9.81) or descending aorta (0.01; odds ratio, 7.68), a completely thrombosed false lumen (0.01; odds ratio, 4.02), and absence of brain ischemia (0.013; odds ratio, 4.74) to be predictors of the lower D-dimer concentration. Compared with patients with a low D-dimer concentration (≤8.3 μg/mL, n=66), patients with a D-dimer concentration >8.3 μg/mL (n=196) had a reduced preoperative platelet count and increased operation time and transfusion volume. In-hospital mortality was elevated in this group (1.5% versus 11.2%; 0.031), although 7-year survival did not differ for hospital survivors (lower versus higher, 93.1% versus 79.1%; =0.21). CONCLUSIONS:D-dimer concentrations are strongly influenced by the extent of dissection and false lumen status. Operative risks are increased in patients with a relatively high D-dimer concentration.
Assessment of the current D-dimer cutoff point in pulmonary embolism workup at a single institution: Retrospective study.
Alhassan S,Bihler E,Patel K,Lavudi S,Young M,Balaan M
Journal of postgraduate medicine
Background:The currently used D-dimer (DD) cutoff point is associated with a large number of negative CT-pulmonary angiographies (CTPA). We hypothesized presence of deficiency in the current cutoff and a need to look for a better DD threshold. Materials and Methods:We conducted a retrospective medical records analysis of all patients who had a CTPA as part of pulmonary embolism (PE) workup over a 1-year period. All emergency room (ER) patients who had DD assay checked prior to CTPA were included in the analysis. We assessed our institutional cutoff point and tried to test other presumptive DD thresholds retrospectively. Results:At our institution 1591 CTPA were performed in 2014, with 1220 scans (77%) performed in the ER. DD test was ordered prior to CTPA imaging in 238 ER patients (19.5%) as part of the PE workup. PE was diagnosed in 14 cases (6%). The sensitivity and specificity of the currently used DD cutoff (0.5 mcg/mL) were found to be 100% and 13%, respectively. Shifting the cutoff value from 0.5 to 0.85 mcg/mL would result in a significant increase in the specificity from 13% to 51% while maintaining the same sensitivity of 100%. This would make theoretically 84 CTPA scans, corresponding to 35% of CTPA imaging, unnecessary because DD would be considered negative based on this presumptive threshold. Conclusions:Our results suggest a significant deficiency in the institutional DD cutoff point with the need to find a better threshold through a large multicenter prospective trial to minimize unnecessary CTPA scans and to improve patient safety.
Plasma D-dimer is not useful in the prediction of deep vein thrombosis after total knee arthroplasty in patients using rivaroxaban for thromboprophylaxis.
Wu Cheng-Ta,Chen Bradley,Wang Jun-Wen,Yen Shih-Hsiang,Huang Chung-Cheng
Journal of orthopaedic surgery and research
BACKGROUND:Venous thromboembolism (VTE) is a serious complication following total joint replacement. The use of rivaroxaban, a highly selective and direct factor Xa inhibitor, has been used widely as a safe and efficacious way to prevent VTE after total joint replacements. However, little is known about the diagnostic efficacy of plasma D-dimer test on deep vein thrombosis (DVT) in patients using rivaroxaban for thromboprophylaxis. The study is aimed to investigate the trend and the diagnostic efficacy of D-dimer test on DVT in patients with primary total knee arthroplasty (TKA) using rivaroxaban for thromboprophylaxis. METHODS:Two hundred TKA patients using rivaroxaban postoperatively as chemical prophylaxis were reviewed. D-dimer levels were checked at 4 h after the surgery and on postoperative days 1 and 4. Venography was used to document the presence of DVT. The Mann-Whitney U test was used to detect the differences in the D-dimer levels at different time points in patients with and without DVT, followed by Bonferroni corrections for p values. Receiver operating characteristics (ROC) curves were constructed to determine the best cutoff values of the D-dimer test at each time point after the surgery. RESULTS:Twenty-nine of the 200 patients were found to have deep vein thrombosis by venography, resulting in an incidence of 14.5%. All patients with DVTs occurred in the distal calf veins, and only one patient was symptomatic. We found significant differences in D-dimer concentration between patients with and without DVT at postoperative day 4. The best cutoff value determined by receiver operating characteristics analysis was 3.8 mg/L at postoperative day 4, with an AUC equal to 63.5%, and a sensitivity, specificity, PPV, and NPV of 58.6, 76, 29.3, and 91.5%, respectively. CONCLUSIONS:Rivaroxaban was effective on reducing DVT in patients undergoing TKA. Because all the DVTs occurred in the leg veins, decreased thrombus volume and size might result in poor accuracy of plasma D-dimer test in prediction or diagnosis of postoperative DVT.
A Novel Clinical Factor, D-Dimer Platelet Multiplication, May Predict Postoperative Recurrence and Prognosis for Patients with Cholangiocarcinoma.
Watanabe Akira,Araki Kenichiro,Hirai Keitarou,Kubo Norio,Igarashi Takamichi,Tsukagoshi Mariko,Ishii Norihiro,Hoshino Kouki,Kuwano Hiroyuki,Shirabe Ken
Annals of surgical oncology
BACKGROUND:Patients with cholangiocarcinoma (CC) have a poor prognosis, and their postoperative survival depends on cancer progression and recurrence. Thus, prognostic markers are needed. The fibrin cleavage product, D-dimer, is associated with malignant progression and recurrence in various cancers, and platelets also are related to tumor progression. This study therefore evaluated a new prognostic factor, D-dimer platelet multiplication (PDM), for predicting prognosis in cases of CC. METHODS:This study retrospectively evaluated 55 cases to determine the correlations of D-dimer, platelet, and PDM levels with patient survival. The cutoff values for D-dimer, platelets, and PDM levels were determined using receiver operating characteristic curve analyses. RESULTS:The recurrence group exhibited significantly higher D-dimer (P = 0.00075) and PDM (P = 0.0000683) levels and a trend toward higher platelet levels (P = 0.117). The optimal cutoff values were 1.3 µg/mL for D-dimer levels, 245 × 104/µL for platelet levels, and 158.2 × 104 µg/mL × µL for PDM levels. Poor recurrence-free survival was associated with high D-dimer levels (P = 0.0428), high platelet levels (P = 0.0498), and high PDM levels (P = 0.00511). Poor cancer-specific survival was associated with high platelet levels (P = 0.0156) and high PDM levels (P = 0.0156). In the multivariate analysis, PDM had the greatest correlation with CC prognosis and independently predicted recurrence (P = 0.00649). CONCLUSION:High D-dimer, platelet, and PDM levels were associated with poor recurrence-free and cancer-specific survivals, with PDM exhibiting the greatest correlation with prognosis. Therefore, PDM may help to predict recurrence and prognosis for patients with CC.
D-dimer predicts postoperative recurrence and prognosis in patients with liver metastasis of colorectal cancer.
Watanabe Akira,Araki Kenichiro,Harimoto Norihumi,Kubo Norio,Igarashi Takamichi,Ishii Norihiro,Yamanaka Takahiro,Hagiwara Kei,Kuwano Hiroyuki,Shirabe Ken
International journal of clinical oncology
BACKGROUND:Colorectal cancer is common, and its incidence is increasing throughout the world. The liver is a major metastatic site, and colorectal liver metastasis (CRLM) has a poor prognosis. Although liver resection is the most effective therapy for CRLM, postoperative recurrence is common. Thus, prognostic markers for CRLM are greatly needed. D-dimer, a fibrin cleavage product, has been shown to be related to colorectal tumor progression, and is also associated with malignant progression and recurrence in various cancers. Therefore, we evaluated the value of D-dimer in predicting the prognosis in CRLM. METHODS:We retrospectively evaluated 90 cases of resected CRLM to determine the correlation between D-dimer and patient survival. The cut-off value for D-dimer levels was determined using receiver operating characteristic curve analysis. RESULTS:Significant differences occurred in the recurrence group with higher D-dimer levels (P = 0.00736*), while the optimal cut-off value was 0.6 µg/mL. High D-dimer levels (≥ 0.6 µg/mL) were associated with poor recurrence-free survival (RFS; P = 0.0000841*) and cancer-specific survival (CSS; P = 0.00615*). In the multivariate analysis, D-dimer correlated with CRLM prognosis and independently predicted RFS (P = 0.0179*). CONCLUSION:High D-dimer levels were associated with poor RFS and CSS. D-dimer was an independent prognostic factor of RFS. Therefore, D-dimer may help predict recurrence and prognosis in patients with CRLM.
Can the use of an age-adjusted D-dimer cut-off value help in our diagnosis of suspected pulmonary embolism? .
Dutton Jonathan,Dachsel Martin,Crane Rachel
Clinical medicine (London, England)
Safe exclusion of pulmonary embolism (PE) is a common problem in acute medicine. Common care pathways usually involve the use of a pre-test probability score with a D-dimer test to aid clinical decision-making. Unfortunately, the specificity of many D-dimer assays decreases with age. This study investigates the role of an age-adjusted D-dimer of 5 x patient's age when the conventional cut-off of the assay is 230 ng/mL. Data was collected retrospectively over a 12-month period from patients who went on to have either computed tomography pulmonary angiography (CTPA) or pulmonary ventilation/perfusion (V/Q) imaging. D-dimers in patients with low or moderate Wells score were analysed for both conventional and age-adjusted cut-offs. The use of an adjusted D-dimer showed a sensitivity of 0.97 (95% CI 0.9-1.0) while the specificity increased from 0.07 (95% CI 0.04-0.11) for the conventional cut-off to 0.32 (95% CI 0.27-0.38) for the age-adjusted cut-off. Using a 5 x patient's age-adjusted D-dimer cut-off is both safe and showed an increased specificity comparable to those published previously on other D-dimer assays.
Age-adjusted cut-off using the IL D-dimer HS assay to exclude pulmonary embolism in patients presenting to emergency.
Lim Ming S,Bennett Ashwini,Chunilal Sanjeev
Internal medicine journal
BACKGROUND/AIM:The ADJUST-PE study showed that an age-adjusted D-dimer (AADD) (age years × 10 ng/mL if >50 years) combined with an unlikely pre-test probability (PTP) can increase the proportion of older patients in whom pulmonary embolism (PE) can be safely excluded, but the IL D-dimer HS assay was not assessed. To assess the ability of the IL D-dimer HS assay to exclude PE using the AADD. METHODS:Retrospective analysis of consecutive patients presenting with symptoms of acute PE to one of three Monash Health Emergency Departments (January 2013-January 2014) who had computed tomography pulmonary angiography. In the group with D-dimer, efficiency (proportion of PE excluded based on a combination of unlikely PTP and negative D-dimer) was determined using (i) current laboratory (200 ng/mL), (ii) conventional (230 ng/mL) and (iii) modified (375 ng/mL if age ≥60 years) AADD cut-offs. RESULTS:A total of 176 patients with D-dimers was included (mean age = 58.5 years; 54.0% males; 71.0% age >50 years). Prevalence of PE in the overall, unlikely and likely PTP groups, was 17.0, 13.0 and 24.6% respectively. In the unlikely PTP group (115 patients), efficiency for the current, conventional, modified and AADD cut-offs was 9.6, 24.3, 30.4 and 37.4% respectively. CONCLUSION:The absolute increase in efficiency of an AADD compared to conventional cut-off using the IL D-dimer HS assay is modest (~10%) and requires prospective validation. Modifying our cut-off to 230 ng/mL and systematic implementation of a clinical algorithm, including D-dimer testing and PTP, is likely a more important first step.
D-Dimer and thrombus burden in acute pulmonary embolism.
Keller Karsten,Beule Johannes,Balzer Jörn Oliver,Dippold Wolfgang
The American journal of emergency medicine
BACKGROUND:Thrombus burden in pulmonary embolism (PE) is associated with higher D-Dimer-levels and poorer prognosis. We aimed to investigate i) the influence of right ventricular dysfunction (RVD), deep venous thrombosis (DVT), and high-risk PE-status on D-Dimer-levels and ii) effectiveness of D-Dimer to predict RVD in normotensive PE patients. METHODS:Overall, 161 PE patients were analyzed retrospectively, classified in 5 subgroups of thrombus burden according to clinical indications and compared regarding D-Dimer-levels. Linear regression models were computed to investigate the association between D-Dimer and the groups. In hemodynamically stable PE patients, a ROC curve was calculated to assess the effectiveness of D-Dimer for predicting RVD. RESULTS:Overall, 161 patients (60.9% females, 54.0% aged >70 years) were included in this analysis. The D-Dimer-level was associated with group-category in a univariate linear regression model (β 0.050 (95%CI 0.002-0.099), P = .043). After adjustment for age, sex, cancer, and pneumonia in a multivariate model we observed an association between D-Dimer and group-category with borderline significance (β 0.047 (95%CI 0.002-0.096), P = .058). The Kruskal-Wallis test demonstrated that D-Dimer increased significantly with higher group-category. In 129 normotensive patients, patients with RVD had significantly higher D-Dimer values compared to those without (1.73 (1.11/3.48) vs 1.17 (0.65/2.90) mg/l, P = .049). A ROC curve showed an AUC of 0.61, gender non-specific, with calculated optimal cut-off of 1.18 mg/l. Multi-variate logistic regression model confirmed an association between D-Dimer >1.18 mg/l and RVD (OR2.721 (95%CI 1.196-6.190), P = .017). CONCLUSIONS:Thrombus burden in PE is related to elevated D-Dimer levels, and D-Dimer values >1.18 mg/l were predictive for RVD in normotensive patients. D-Dimer levels were influenced by DVT, but not by cancer, pneumonia, age, or renal impairment.
Clinical significance of plasma D-dimer and fibrinogen in digestive cancer: A systematic review and meta-analysis.
Lin Yan,Liu Zhihui,Qiu Yufen,Zhang Jinyan,Wu Huini,Liang Rong,Chen Guoying,Qin Gang,Li Yongqiang,Zou Donghua
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
BACKGROUND:Abnormalities of coagulation and fibrinolysis are frequently observed in cancer patients. Emerging data suggested that plasma D-dimer and fibrinogen levels correlated with tumor stage and prognosis in several cancer types. The aim of this study is to systematically review the prognostic value of plasma D-dimer and fibrinogen in digestive cancers. MATERIALS AND METHODS:We searched major database for manuscripts reporting the effect of pretreatment plasma d-dimer or fibrinogen on survival of digestive cancer patients. Revman5.3 and R were the software used for analysis. Pooled multivariable-adjusted hazard ratios (HR) for overall survival (OS) were calculated in all patients and many different subgroup analyses by stratifying on metastasis stage, tumor type, ethnicity, cutoff points and average age. RESULTS:37 original studies were included for analysis. Increased levels of plasma D-dimer showed stronger association with worse OS than fibrinogen in digestive cancer (HR = 2.06, 95% CI 1.79-2.38; HR = 1.60, 95% CI 1.44-1.79). The highest adverse impacts of elevated plasma D-dimer and fibrinogen on OS were revealed in colorectal cancer (HR = 2.32, 95% CI 1.89-2.85; HR = 2.20, 95% CI 1.24-3.90). The negative prognostic effects of high plasma D-dimer enhanced in metastatic patients when compared with non-metastatic digestive cancer patients, while high plasma D-dimer was more predictive non-metastatic patients. CONCLUSIONS:Both of pretreatment plasma D-dimer and fibrinogen were robust predictors of poor survival in digestive cancer patients with different traits. Further studies are warranted to verify their roles on cancer prognosis.
Rapid Systematic Review: Age-Adjusted D-Dimer for Ruling Out Pulmonary Embolism.
Barth Bradley E,Waligora Grzegorz,Gaddis Gary M
The Journal of emergency medicine
BACKGROUND:Pulmonary embolism (PE) is a disease diagnosed relatively frequently in emergency departments (EDs). Evidence suggests that improved decision making may decrease inappropriate testing, unnecessary radiation exposure, and non-beneficial treatment. Several studies have looked at the utility and safety of age-adjusting the D-dimer levels used to safely rule out PE. OBJECTIVE:This rapid systematic review sought to answer the question: Can an age-adjusted D-dimer be used to safely rule out PE in patients over 50 years old? METHODS:We performed a structured review of PubMed from January 2012 to January 2018 limited to reports involving human subjects and written in the English language and containing relevant keywords. The highest-quality studies were then reviewed in a structured format. RESULTS:One hundred and eleven papers were identified for further review. Eight articles were determined to be appropriate for inclusion in this summary. These studies all used patient age (in years over 50) × 10 μg/L (fibrinogen equivalent units) as their definition of an age-adjusted D-dimer. CONCLUSIONS:Age-adjusted D-dimer cutoff values, in combination with a non-high clinical probability, is safe and effective to essentially rule out PE in ED patients.
Diagnosis of pulmonary embolism in the elderly: adherence to guidelines and age-adjusted D-dimer concentration values.
Lozano-Polo Laura,Puig-Campmany Mireia,Herrera-Mateo Sergio,Mateo-Roca Miriam,Santos-Rodríguez José Alberto,Benito-Vales Salvador
Emergencias : revista de la Sociedad Espanola de Medicina de Emergencias
OBJECTIVES:. The main purpose was to assess our emergency department's level of adherence to clinical practice guidelines (CPGs) for the diagnosis of pulmonary embolism in different age groups. The secondary aims were to study the utility and estimated the number of avoidable CT angiography with this approach of age-adjusted D-dimer concentrations in combination with the Wells score in the diagnosis of pulmonary embolism. MATERIAL AND METHODS:Retrospective observational study of a series of hemodynamically stable patients suspected of having pulmonary embolism in the emergency department of a tertiary care university hospital in 2012. Cases were identified in hospital discharge records on the basis of orders for D-dimer assays and computed tomography (CT) angiography of pulmonary arteries justified by suspicion of pulmonary embolism. We analyzed the degree of adherence to CPGs according to age groups, calculated the specificity and sensitivity of combining age-adjusted D-dimer test results and the Wells score, and estimated the number of potentially avoidable CT angiography procedures. RESULTS:We found a total of 785 patients (mean age, 69 years; range, 18-97 years) suspected of having pulmonary embolism; 403 (51.3%) were women. Significant differences were detected in adherence to CPGs, depending on which clinical prediction models were used and patient age (50 years or younger, 69.7%-76.5% adherence; 65-74 years, 32.3%-53.2%; 75-84 years, 29.1%-46.8%; 85-89 years, 32.7%-41.8%; and 90 years or older, 24.4%-46.7%). Adherence was increased when D-dimer test result and the simplified Wells score were combined (increments of 10.4%, 8.0%, 13.6%, 11.1%, respectively in the following age groups: 65-74 years, 75-84 years, 85-89 years, and 90 years or older). Using an ageadjusted D-dimer cut-point increased diagnostic specificity (34.2% without such a cut-point vs 45.8% with one). The positive predictive value of the test also increased when an age-adjusted D-dimer cut-point was used (to 11.4%, from 9.6% without age adjustement). Seventy CT angiograph procedures (12.5%) could have been avoided by using age-adjusted cut-points. CONCLUSION:We observed different degrees of age-related adherence to CPGs in cases in which pulmonary embolism was suspected. Using the simplified Wells score combined with an age-adjusted cut-point for D-dimer assay positivity improved the specificity and positive predictive value of the D-dimer assessment in comparison with standard practice. Using age-adjusted D-dimer cut-points could decrease the number of pulmonary artery CT angiograms required.
Prognostic value of fibrinogen and D-dimer-fibrinogen ratio in resectable gastrointestinal stromal tumors.
Cai Hua-Xia,Li Xu-Qi,Wang Shu-Feng
World journal of gastroenterology
AIM:To investigate the prognostic value of preoperative fibrinogen concentration (FIB) and D-dimer-fibrinogen ratio (DFR) in gastrointestinal stromal tumors (GISTs). METHODS:The purpose of this study was to retrospectively analyze 170 patients with GISTs who were admitted to our hospital from January 2010 to December 2015. The optimal cutoff values of related parameters were estimated by receiver operating characteristic (ROC) curve analysis. The recurrence free survival (RFS) rate was evaluated using Kaplan-Meier curves. Univariate analysis and multivariate Cox regression models were used to analyze the prognostic factors of GISTs. The relationship between the FIB, D-dimer, DFR, platelet count (PLT), and the clinicopathological features of GISTs was described by the chi-square test or nonparametric rank sum test (Mann-Whitney test). RESULTS:In ROC analysis, the optimal cutoff values of FIB, D-dimer, DFR, and PLT were 3.24 g/L, 1.24 mg/L, 0.354, and 197.5 (× 10/L), respectively. Univariate analysis and the Kaplan-Meier survival curve showed that FIB, D-dimer, DFR, PLT, National Institutes of Health (NIH) risk category, tumor size, tumor location, and mitotic index were significantly relevant to the 3-year and 5-year survival rate of patients ( < 0.05). Cox multivariate regression analysis illustrated that FIB (: 0.108, 95%CI: 0.031-0.373), DFR (: 0.319, 95%CI: 0.131-0.777), and NIH risk category (: 0.166, 95%CI: 0.047-0.589) were independent prognostic factors of the RFS rate ( < 0. 05). Moreover, FIB, D-dimer, DFR, and PLT were correlated with the clinical features of GISTs. CONCLUSION:FIB, D-dimer, DFR, and PLT are all related to the prognosis of GISTs. Moreover, FIB and DFR may be independent risk factors for predicting the prognosis of resectable GISTs.
d-Dimer Assessment Improves the Simplified Pulmonary Embolism Severity Index for In-Hospital Risk Stratification in Acute Pulmonary Embolism.
Kozlowska Marta,Plywaczewska Magdalena,Koc Marcin,Pacho Szymon,Wyzgal Anna,Zdonczyk Olga,Furdyna Aleksandra,Ciurzynski Michal,Kurnicka Katarzyna,Jankowski Krzysztof,Lipinska Anna,Palczewski Piotr,Bienias Piotr,Pruszczyk Piotr
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
d-dimer (DD) levels are used in the diagnostic workup of suspected acute pulmonary embolism (APE), but data on DD for early risk stratification in APE are limited. In this post hoc analysis of a prospective observational study of 270 consecutive patients, we aimed to optimize the discriminant capacity of the simplified pulmonary embolism severity index (sPESI), an APE risk assessment score currently used, by combining it with DD for in-hospital adverse event prediction. We found that DD levels were higher in patients with complicated versus benign clinical course 7.2 mg/L (25th-75th percentile: 4.5-27.7 mg/L) versus 5.1 mg/L (25th-75th percentile: 2.1-11.2 mg/L), P = .004. The area under the curve of DD for serious adverse event (SAE) was 0.672, P = .003. d-dimer =1.35 mg/L showed 100% negative predictive value for SAE and identified 11 sPESI ≥1 patients with a benign clinical course, detecting the 1 patient with SAE from sPESI = 0. d-dimer >15 mg/L showed heart rate for SAE 3.04 (95% confidence interval [CI]: 1-9). A stratification model which with sPESI + DD >1.35 mg/L demonstrated improved prognostic value when compared to sPESI alone (net reclassification improvement: 0.085, P = .04). d-dimer have prognostic value, values <1.35 mg/L identify patients with a favorable outcome, improving the prognostic potential of sPESI, while DD >15 mg/L is an independent predictor of SAE.
D-dimer >2.785 μg/ml and multiple infarcts ≥3 vascular territories are two characteristics of identifying cancer-associated ischemic stroke patients.
Wang Jing-Ye,Zhang Gao-Jia,Zhuo Sheng-Xia,Wang Kai,Hu Xiao-Peng,Zhang Hui,Qu Lin-di
BACKGROUND:The patterns and mechanisms underlying stroke in cancer patients differ from those of the conventional etiology. In this study, we further investigated the characteristics distinguishing cancer-associated ischemic stroke (CAIS) and the relationship of D-dimer value with CAIS. METHODS:Sixty-one acute ischemic stroke patients with cancer (cancer group) and 76 stroke patients without cancer (control group) were recruited. Cerebrovascular distribution was divided into 3 circulations and 23 vascular territories, and acute multiple brain infarcts (AMBIs) were defined as discrete MRI diffusion-weighted imaging (DWI) lesions in >1 vascular territory. RESULTS:Cancer patients had higher average D-dimer and fibrinogen degradation product values, and fewer stroke risk factors. The numbers of infarct-affected vascular territories, AMBIs, and AMBIs in multiple circulations were significantly higher in the cancer group. Receiver operating characteristic analysis showed that the cutoff value of D-dimer was 2.785 μg/ml; and above features were particularly evident in cancer patients whose D-dimer values were >2.785 μg/ml, while those with D-dimer values ≤2.785 μg/ml were similar to controls. CONCLUSIONS:D-dimer >2.785 μg/ml may be an effective cutoff value and a sensitive index for identifying CAIS patients. AMBIs in ≥3 vascular territories and AMBIs in both the anterior and posterior circulations are two imaging characteristics of CAIS.
Decision-Making with D-Dimer in the Diagnosis of Pulmonary Embolism.
Sendama Wezi,Musgrave Kathryn M
The American journal of medicine
The measurement of D-dimer can provide useful information to aid in the diagnosis of patients with suspected venous thromboembolism. D-dimer measurement in conjunction with adequate estimation of pretest probability can facilitate the safe discharge of patients with suspected pulmonary embolism and limit unnecessary investigation or anticoagulation. We review clinical decision-making strategies in the diagnosis of pulmonary embolism and propose means to minimize diagnostic error that might arise from knowledge of the D-dimer result prior to clinical assessment.
Evaluating the analytical performance of four new coagulation assays for the measurement of fibrinogen, D-dimer and thrombin time.
Kitchen Steve,Geisen Ulrich,Kappelmayer Janos,Quehenberger Peter,Lowe Anna,Jones Robert,Miles Gabrielle,Boehm Jana G,Rozsnyai Gergely
International journal of laboratory hematology
INTRODUCTION:New laboratory methods to measure haemostatic function require careful assessment before routine use. We evaluated the analytical performance of four new coagulation assays for the measurement of fibrinogen by Clauss assay, prothrombin time-derived fibrinogen, thrombin time and D-dimer levels. METHODS:The four assays were evaluated on the cobas t 711 and cobas t 511 analysers at four centres in Europe. Analytical performance and method comparisons with other commercially available assays were performed according to Clinical and Laboratory Standards Institute guidelines (EP09-A3, EP05-A3) using residual anonymized human sodium citrate (3.2% [0.109M]) plasma samples. Lot-to-lot variability and the equivalency of each assay on the cobas t 711 and cobas t 511 analysers were also assessed. RESULTS:Overall, coefficients of variance were ≤4.1% and ≤8.6% for within-run precision and total reproducibility, respectively. Method comparison experiments showed good or acceptable agreement for each assay compared with their respective comparator method, and equivalency was demonstrated for the two cobas t platforms (Pearson's correlation coefficient ≥0.991). A high level of consistency was observed between lots for all four assays (Pearson's correlation coefficient ≥0.994). CONCLUSION:This multicentre study demonstrates excellent analytical performance for four new coagulation assays on the cobas t 711 and cobas t 511 analysers.
Prognostic and predictive value of plasma D-dimer levels in patients with small-cell lung cancer.
Zhang Cuicui,Jia Yongsheng,Jia Yanan,Zhang Xiaoling,Li Kai
International journal of clinical oncology
BACKGROUND:To investigate the predictive value of plasma D-dimer levels for short-term therapeutic effect and progression-free survival (PFS) in patients with small-cell lung cancer (SCLC); and to analyze the correlation between baseline plasma D-dimer levels and other clinicopathological features. The aim of the study was to investigate whether the levels of plasma D-dimer could serve as a predictive and prognostic factor in patients with SCLC. METHODS:A retrospective review of the clinicopathological data of 160 patients with pathologically confirmed SCLC, who were treated at the Department of Thoracic Oncology of Tianjin Medical University Tumor Institute and Hospital between June 2011 and June 2016, was performed. At the same time, we collected 100 patients with benign pulmonary diseases as a control group. The correlations between baseline plasma D-dimer levels and other clinical features, therapeutic effect and PFS were analyzed statistically. RESULTS:The level of plasma D-dimer in patients with SCLC was significantly higher than that of patients with benign pulmonary diseases (P = 0.001). The PFS of patients with elevated D-dimer levels before therapy were significantly shorter than that of patients with normal D-dimer levels (6.0 versus 7.5 months, P = 0.013). The patients whose plasma D-dimer level always (before and after treatment) in the normal range have the best prognosis, and continuously elevated D-dimer carried out a poor prognosis (8.0 versus 5.0 months). According to multivariate analysis, elevated D-dimer level was confirmed to be an independent prognostic factor for worse survival (P = 0.029). The level of D-dimer was associated with tumor stage, the level of neuron-specific enolase, the presence of distant metastasis, hyponatremia, and the Karnofsky performance status score; and levels decreased when therapy was effective, but increased when the disease progressed. CONCLUSIONS:High levels of baseline plasma D-dimer may indicate advanced disease stage and poor prognosis. Therefore, plasma D-dimer levels could serve as a predictive and prognostic factor in patients with SCLC.
Safety of D-dimer testing as a stand-alone test for the exclusion of deep vein thrombosis as compared with other strategies.
Fronas S G,Wik H S,Dahm A E A,Jørgensen C T,Gleditsch J,Raouf N,Klok F A,Ghanima W
Journal of thrombosis and haemostasis : JTH
Essentials The aim of deep vein thrombosis (DVT) diagnostic work-up is to maximize both safety and efficiency. We explored whether D-dimer is safe and efficient as a stand-alone test to exclude DVT. Our findings suggest it is a safe, efficient and simplified diagnostic strategy. The safety of age-adjusted D-dimer as a stand-alone test requires further investigation. SUMMARY: Background Several strategies for safely excluding deep vein thrombosis (DVT) while limiting the number of imaging tests have been explored. Objectives To determine whether D-dimer testing could safely and efficiently exclude DVT as a stand-alone test, and evaluate its performance as compared with strategies that incorporate the Wells score and age-adjusted D-dimer. Patients/Methods We included consecutive outpatients referred with suspected DVT to the Emergency Department at Østfold Hospital, Norway. STA-Liatest D-Di PLUS D-dimer was analyzed for all patients. Patients with a D-dimer level of ≥ 0.5 μg mL were referred for compression ultrasonography (CUS). In patients with a D-dimer level of < 0.5 μg mL , no further testing was performed and anticoagulation was withheld. Patients were followed for 3 months for venous thromboembolism (VTE). Results Of the 913 included patients, 298 (33%) had a negative D-dimer result. One hundred and seventy-three patients (18.9%) were diagnosed with DVT at baseline. One of 298 patients had DVT despite having a negative D-dimer result, resulting in a failure rate of 0.3% (95% confidence interval [CI] 0.1-1.9%). Adding the modified Wells score would have yielded a failure rate of 0.0% (95% CI 0.0-1.8%) while necessitating 87 more CUS examinations. Age-adjusted D-dimer as a stand-alone test would have necessitated 80 fewer CUS examinations than fixed D-dimer as a stand-alone test, at the cost of a failure rate of 1.6% (95% CI 0.7-3.4%). Conclusions This outcome study shows that a negative high-sensitivity D-dimer result safely excludes DVT in an outpatient population, and necessitates fewer CUS than if used in combination with Wells score. The safety of stand-alone age-adjusted D-dimer needs further assessment in prospective outcome studies.
D-dimer: Preanalytical, analytical, postanalytical variables, and clinical applications.
Favresse Julien,Lippi Giuseppe,Roy Pierre-Marie,Chatelain Bernard,Jacqmin Hugues,Ten Cate Hugo,Mullier François
Critical reviews in clinical laboratory sciences
D-dimer is a soluble fibrin degradation product deriving from the plasmin-mediated degradation of cross-linked fibrin. D-dimer can hence be considered a biomarker of activation of coagulation and fibrinolysis, and it is routinely used for ruling out venous thromboembolism (VTE). D-dimer is increasingly used to assess the risk of VTE recurrence and to help define the optimal duration of anticoagulation treatment in patients with VTE, for diagnosing disseminated intravascular coagulation, and for screening medical patients at increased risk of VTE. This review is aimed at (1) revising the definition of D-dimer; (2) discussing preanalytical variables affecting the measurement of D-dimer; (3) reviewing and comparing assay performance and some postanalytical variables (e.g. different units and age-adjusted cutoffs); and (4) discussing the use of D-dimer measurement across different clinical settings.
D-dimer is associated with arterial and venous coronary artery bypass graft occlusion.
Parolari Alessandro,Cavallotti Laura,Andreini Daniele,Myasoedova Veronika,Banfi Cristina,Camera Marina,Poggio Paolo,Barili Fabio,Pontone GianLuca,Mussoni Luciana,Centenaro Chiara,Alamanni Francesco,Tremoli Elena,
The Journal of thoracic and cardiovascular surgery
OBJECTIVE:In this observational prospective study, we assessed the role of clinical variables and circulating biomarkers in graft occlusion at 18 months to identify a signature for graft occlusion. METHODS:A total of 330 patients undergoing primary elective coronary artery bypass grafting were enrolled. Blood collection for biomarker assessment was performed before surgery and discharge. Patients were then scheduled to undergo coronary computed tomography angiography at 18 months follow-up, and 179 patients underwent coronary computed tomography angiography 18 ± 2 months postoperatively. RESULTS:There were 46 of 503 (9.1%) occluded grafts; of these, 29 (63%) were venous and 17 (37%) were arterial grafts; overall, 43 of 179 patients (24%) had at least 1 occluded graft. Logistic mixed effects model assessing independent factors associated with graft occlusion identified that lower D-dimer levels at baseline (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.36-4.89; P = .00) and total protein content at discharge (OR, 1.09; 95% CI, 1.01-1.19; P = .028) were related to overall graft occlusion at follow-up, along with an arterial graft other than the left internal thoracic artery (OR, 2.92; 95% CI, 1.24-6.9; P = .078); moreover, a venous graft emerged was possibly associated with graft occlusion (OR, 1.51; 95% CI, 0.95-2.39; P = .078). By separately analyzing saphenous vein and arterial grafts, D-dimer levels (OR, 2.67; 95% CI, 1.15-6.2; P = .022 and OR, 2.5; 95% CI, 1.01-7.0; P = .05 for venous and arterial graft, respectively) were still associated with arterial and venous graft occlusion at follow-up. CONCLUSIONS:We identified D-dimer as a biomarker associated with arterial and venous grafts occlusion. This may help stratify patients at risk of graft failure and identify new molecular targets to prevent this complication.
The Evaluation of D-Dimer Levels for the Comparison of Fibrinogen and Fibrin Units Using Different D-Dimer Kits to Diagnose VTE.
Hasegawa Masahiro,Wada Hideo,Yamaguchi Toshio,Wakabayashi Hiroki,Fujimoto Naoki,Matsumoto Takeshi,Hasegawa Kei,Yamada Norikazu,Ito Masaaki,Yamashita Yoshiki,Katayama Naoyuki,Nakatani Kaname,Sudo Akihiro
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
The cutoff values of D-dimer levels for diagnosing or predicting the occurrence of deep vein thrombosis (DVT) were evaluated in preoperative patients and compared to those in non-DVT patients. The levels of 8 different D-dimers were measured using the latex agglutination method or enzyme immunoassay before surgery in 262 orthopedic surgery patients to diagnose subclinical DVT or predict postoperative DVT. There were 15 patients with subclinical DVT and 47 with postoperative DVT, but 200 patients had no DVT at all. All 8 plasma D-dimer values were significantly higher in the patients with subclinical or postoperative DVT than in those without DVT or in healthy volunteers. There were differences in the cutoff values between the assays highly sensitive for low D-dimer levels and wild-range assays of D-dimers. Some D-dimer assays might therefore be more useful than others for diagnosing low levels of D-dimer. Although the measurement of D-dimer levels was useful for diagnosing subclinical DVT and predicting the risk of DVT, the cutoff values for the diagnosis or prediction of DVT varied. The cutoff values for the prediction of postoperative DVT were ≥1.7 µg/mL (D-dimer A-D) and ≥1.0 µg/mL (D-dimer E-H).
Clinical characteristics of children evaluated for suspected pulmonary embolism with D-dimer testing.
Kanis Jessica,Pike Jonathan,Hall Cassandra L,Kline Jeffrey A
Archives of disease in childhood
BACKGROUND:We sought to determine clinical variables in children tested for suspected pulmonary embolism (PE) that predict PE+ outcome for the development of paediatric PE prediction rule. METHODS:Data were collected by query of a laboratory database for D-dimer from January 2004 to December 2014 for a large multicentre hospital system and the radiology database for pulmonary vascular imaging in children aged 5-17. Using explicit, predefined methods, trained abstractors, determined if D-dimer was sent in the evaluation of PE and then recorded predictor data which was tested for association with PE+ outcome using univariate techniques. RESULTS:D-dimer was ordered in 526 children for clinical suspicion of PE. Thirty-four of 526 were PE+ (6.4%, 95% CI 4.3% to 8.7%). The radiology database identified 17 additional patients with PE (n=51 PE+ total). Children evaluated for PE were primarily in the ED setting (80%), teenagers (88%) and 2:1 female:male. Children with PE had higher mean heart and higher respiratory rate and a lower pulse oximetry and haemoglobin concentration. On univariate analysis, five conditions were more frequent in PE+ compared with no PE: surgery, central line, limb immobility, prior PE or deep vein thrombosis and cancer. CONCLUSIONS:The rate of PE diagnosis in children with D-dimer was 6.4%, similar to that seen in adults; most children with PE are over 13 years and had clinical predictors known to increase probability of PE in symptomatic adults. Future studies should use these criteria to develop a clinical decision rule for PE in children.
Preoperative plasma D-dimer levels predict survival in patients with operable non-small cell lung cancer independently of venous thromboembolism.
Zhang P P,Sun J W,Wang X Y,Liu X M,Li K
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
BACKGROUND AND AIMS:D-dimer is a stable end product of fibrin degradation that is associated with advanced tumor stage and poor prognosis in lung cancer patients. Venous thromboembolism (VTE) is a frequent complication of cancer and is associated with a poor prognosis in cancer patients. The purpose of the study is to elucidate whether the increased mortality in non-small cell lung (NSCLC) patients with elevated D-dimer levels is independent of VTE. PATIENTS AND METHODS:A retrospective review was conducted of 232 patients with operable NSCLC from January 2007 to June 2008. All the patients underwent a pneumonectomy, lobectomy or wedge resection. We assessed the ability of preoperative plasma D-dimer levels to predict 1-year mortality and overall survival among them, and a multivariable Cox proportional-hazard regression analysis was performed after controlling for the following potential confounding factors: age, gender, TNM stage, histology, tumor size, VTE and surgical interventions. RESULTS:The overall 1-year survival rate was 91.4% (95% confidence interval (CI), 82.7-94.8%), with a 76.5% survival (95% CI, 71.4-81.6%) in the high D-dimer group and a 93.9% survival (95% CI, 86.4-97.9%) in the normal D-dimer group. Comparing the high D-dimer group with the normal D-dimer group, the adjusted hazard ratio for 1-year mortality and overall survival was 3.19 (95% CI, 1.18-7.12) and 1.54 (95% CI, 1.11-2.78) respectively. CONCLUSION:Our study concluded that the preoperative plasma D-dimer level is an important prognostic biomarker in patients with operable NSCLC that is independent of VTE.
Value of fibrinogen and D-dimer in predicting recurrence and metastasis after radical surgery for non-small cell lung cancer.
Jiang He-Guo,Li Jian,Shi Shun-Bing,Chen Ping,Ge Li-Ping,Jiang Qian,Tang Xin-Ping
Medical oncology (Northwood, London, England)
Previous studies have suggested an association between preoperative plasma fibrinogen and D-dimer levels and prognosis in patients with non-small cell lung cancer (NSCLC) who underwent surgery. In this study, we evaluate the value of pre- and post-operative plasma fibrinogen and D-dimer levels and changes in the levels of the two markers between before and after operation in predicting tumor recurrence and metastasis in NSCLC patients who undergoing radical surgery. One hundred and eighty-four patients with I-IIIA NSCLC were enrolled in this study, and plasma fibrinogen and D-dimer levels were measured in these patients before and after surgery, respectively. The results showed that pre- and post-operative plasma fibrinogen and D-dimer levels were significantly higher in NSCLC patients than in control group. Pre- and post-operative plasma fibrinogen and D-dimer positivities were significantly correlated with tumor recurrence (P = 0.020 and P = 0.001 for fibrinogen, and P = 0.027 and P = 0.001 for D-dimer). Moreover, there was a significant link between the decrease in fibrinogen and D-dimer levels after surgery and tumor recurrence (P = 0.014 and P = 0.018). Patients with pre- and post-operative fibrinogen and D-dimer positivities had a shorter disease-free survival (DFS) than those without (P = 0.002 and P < 0.001 for fibrinogen, and P = 0.003 and P = 0.001 for D-dimer). Multivariate Cox regression analyses revealed that pre- and post-operative fibrinogen and D-dimer positivities were independent predictors for unfavorable DFS. Our results indicate that pre- and post-operative plasma fibrinogen and D-dimer levels may be useful biomarkers in predicting tumor recurrence and metastasis for patients who undergo curative surgery.
[Analysis of the factors associated with abnormal coagulation and prognosis
in patients with non-small cell lung cancer].
Li Yanhua,Wei Suju,Wang Junyan,Hong Lei,Cui Lige,Wang Cai
Zhongguo fei ai za zhi = Chinese journal of lung cancer
BACKGROUND AND OBJECTIVE:The activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are associated with high risk of invasion, metastases, and negative final outcomes. Non-small cell lung cancer (NSCLC) accounts for approximately 80% to 85% of all lung malignancies. This study aims to investigate the prognostic value of blood coagulation tests for NSCLC and provide a reference to patients on the prevention and treatment of thrombophilia. METHODS:Data were collected from 604 cases of hospitalized patients with histologically confirmed NSCLC from January 2009 to December 2012 at the Fourth Hospital of Hebei Medical University. Data included the related indexes of coagulation function in patients before treatment [(i.e., prothrombin time (PT), prothrombin time activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib), D-dimer, and platelet count)], as well as sex, age, pathological type, TNM stage, and lymph node status. Fifty control subjects without cancer were included in the analysis. Statistical analysis was conducted by using SPSS 13.0 software. RESULTS:The plasma level of all coagulation tests including D-dimer, Fib, PT, APTT, INR, and platelet counts revealed statistically significant differences between the patient and control group (P<0.001 for all variables; P=0.001,5 and P=0.004,5 for Fib and platelet counts, respectively). The squamous subtype exhibited high plasma Fib levels (P<0.001) compared with adenocarcinoma cell lung cancer patients. Fib and PLT levels increased (P<0.001 and P=0.014, respectively), and aPTT decreased (P<0.001) in patients at stages III and IV compared with those in patients at stages I and II. aPTT decreased significantly (P<0.001), and Fib and D-dimer levels increased (P<0.001 and P=0.048, respectively) in N1-3 patients with NSCLC compared with those of N0 patients. Prolonged PT and INR, high plasma Fib levels, and low PTA levels had statistically significant adverse effects on survival (P=0.032, P=0.001, P<0.001, and P=0.005, respectively). Multivariate analyses revealed that only increased INR was associated with a decreased survival rate in the related indexes of coagulation function (P=0.017). CONCLUSIONS:Patients who have lung adenocarcinoma and/or lymph node metastasis at advanced stages of NSCLC are prone to thrombophilia. Prolonged PT and INR was associated with poor prognosis, and elevated INR was independently associated with a decreased survival rate. PT and INR are promising prognostic markers of NSCLC.
Prognostic role of preoperative platelet, fibrinogen, and D-dimer levels in patients with non-small cell lung cancer: A multicenter prospective study.
Hou Can,Jiang Feng,Ma Haitao,Zhu Quan,Wang Zhonglin,Zhao Biao,Xue Tao,Tan Sheng,Yang Rusong,Qian Yongxiang,Luo Xuan,Zhao Ming,Xu Xing,Chen Liang,Li Jiayuan
BACKGROUND:The relationships between coagulation factors and non-small cell lung cancer (NSCLC) prognosis have been intensively studied. However, no previous study has investigated the combined effects of preoperative platelet (PLT), fibrinogen (FIB), and D-dimer (D-D) levels on the prognosis of NSCLC. METHODS:A multicenter prospective study was conducted over seven hospitals. A total of 395 patients diagnosed with operable NSCLC for the first time were included and followed-up until disease progression or the end of the study. Baseline demographic and clinicopathological information, and preoperative coagulation test results were collected for each patient. Univariate and multilevel survival analyses were conducted using Cox regression and shared frailty models. RESULTS:Multilevel analyses revealed that there was a marginally significant association between elevated PLT level (> 215 × 10 /L) and unfavorable progression-free survival (PFS) (hazard ratio 2.42, P = 0.05), whereas preoperative FIB and D-D were not significant prognostic factors for PFS (P = 0.31 and 0.30, respectively). Compared to patients with one elevation of the three coagulation factors, patients with at least two elevations of the three factors had a significantly higher risk of cancer progression (hazard ratio 4.62, P = 0.02). CONCLUSION:The number of elevated preoperative coagulation factors may have a significant effect on PFS and could be used to predict the prognosis of NSCLC patients after surgery. Future studies are warranted to further investigate the interactions between these three coagulation factors.
Fibrin D-dimer in thrombogenic disorders.
Matsuo T,Kobayashi H,Kario K,Suzuki S
Seminars in thrombosis and hemostasis
Measurement of D-dimer (fibrin degradation product) is important for determining not only the activation of fibrinolysis but also the severity of a hypercoagulable state. However, fibrin degradation products are in variable, and the reactivity to cross-linked fibrin degradation products produced during fibrin degradation differs depending on the kind of antibody used against D-dimer. In patients with disseminated intravascular coagulation or earthquake-induced mental and physical stress and in patients after percutaneous transluminal coronary angioplasty, all of which are associated with acute fibrin formation and degradation, some discrepancies between two methods of D-dimer detection, automated latex agglutination assay (LPIA) and enzyme-linked immunosorbent assay (Stago), were found. No discrepancies in persistent fibrin formation and degradation were found among the healthy elderly, patients with lacunar stroke, and patients with coronary artery disease, almost all of whom had levels under 5.0 microg/mL, as determined by both methods. Evidence of persistently increased intravascular coagulation and fibrin turnover in patients with atherosclerotic disease was found. The cleavage of cross-linked fibrin by plasmin results in a production of fibrin degradation products, mostly contained D-dimer domains. Although the clinical utility of D-dimer can be achieved by their detection with specific antibodies, measurement of D-dimer as high-molecular-weight fragments may be useful to determine whether patients will undergo further fibrin degradation. When intermediate products of the degradation process need to be assessed, D-dimer level measurement by LPIA may serve as a suitable marker for ongoing fibrinolysis.
Validation, calibration, and specificity of quantitative D-dimer assays.
Seminars in vascular medicine
Assays for D-dimer antigen are based on monoclonal antibodies reactive with epitopes found on fibrin fragment D-dimer but not on fibrinogen fragment D, other fibrinogen degradation products, or native fibrinogen. The antibodies react with conformational epitopes generated by factor XIII-induced linkage of the C-terminal appendages of the fibrin gamma-chains of adjacent D-domains within a fibrin polymer. For some monoclonal antibodies, degradation of the cross-linked fibrin compound by plasmin is an additional requirement for the generation of the epitope. In clinical plasma samples, D-dimer antigen assays detect an array of fibrin compounds of different molecular weights, including fibrin fragment D-dimer as well as higher-molecular-weight fibrin degradation products and fibrin X-oligomers. Most D-dimer antigen represents cross-linked soluble fibrin present in circulation rather than degradation products from particulate clots. Due to differences in epitope reactivity, harmonization of D-dimer antigen assays can only be achieved with standard preparations containing a similar variety of cross-linked fibrin compounds. Assay technologies include manual latex agglutination assays, automated latex-enhanced light-scattering immunoassays, enzyme-linked immunoassays, and others.
Generation and characterization of D-dimer specific monoclonal antibodies for use in latex agglutination test.
Török-Nagy Beáta,Antal József,Dénes Béla
The commercially available D-dimer assays used in the clinical practice often show differences in the results, and their specificity and sensitivity are rather unsatisfactory. Our aim was to develop a new monoclonal antibody against D-dimer with a proper specificity, and estimating its suitability using in a latex agglutination diagnostic test. Monoclonal antibodies were generated using hybridoma technology. Their titer was determined by a self-developed ELISA method. The cross-reactions of the antibodies were tested. Characterization of the epitope specificity of a selected antibody was performed through digestion of D-dimer followed by Western blotting. The amino acid sequences of the active antigen fragments were determined. According to the ELISA results, 38 cell groups were constated as antibody-producing hybridomas, among them 7 gave raised titer of antibody and were cloned. Based on the cross-reaction analysis, none of the antibodies gave cross-reaction with fibrin-E and fibrinogen-E fragments but reacted with fibrin D and fibrinogen D fragments. A low cross-reaction was showed with fibrinogen and fibrin X and Y. Contrary to the others, antibody 2B9 gave no cross-reaction with fibrinogen and reacted weakly with fibrin X and Y fragments. According to the epitope analysis the antibody 2B9 binds to amino acids 94-99 and to amino acids 140-147 on the beta chain and it recognizes the amino acids 23-32 and 93-98 on the gamma chain of D-dimer. Considering the characteristics of the above mentioned monoclonal antibody 2B9, we found that it is suitable to be a basis for a D-dimer diagnostic test with proper specificity.
Biosensing of D-dimer, making the transition from the central hospital laboratory to bedside determination.
Tasić Nikola,Paixão Thiago R L C,Gonçalves Luís Moreira
Since the disclosure of the fibrinogen degradation mechanism, around half a century ago, a significant number of papers have been published related to the clinical relevance of D-dimer, a molecule immune to additional enzymatic decomposition by plasmin. Due to the obliquity of regulating blood coagulation in pathological events, the number of diseases and conditions associated with abnormal levels of D-dimer includes deep vein thrombosis, pulmonary embolism, sepsis, myocardial infarction, disseminated intravascular coagulation, among many others. D-dimer not only is an important player in medical diagnosis but also its role as a prognosis biomarker is being revealed. However, the number of analytical alternative methods has not accompanied this trend, even though novel simple point-of-care devices would certainly boost the relevance of D-dimer in emergency medicine. Some reasons for that could be related to the fact that D-dimer is a challenging analyte present in complex samples like blood. In this manuscript, subsequent to a fibrinogen degradation process introduction, it is provided a historical overview of the early D-dimer assays, followed by an extended focus on innovative solutions, with a spotlight on the electrochemical bioanalytical devices. The discussion is accompanied with a critical analysis and concluding thoughts concerning future perspectives.
Application value of Caprini risk assessment model and elevated tumor-specific D-dimer level in predicting postoperative venous thromboembolism for patients undergoing surgery of gynecologic malignancies.
Shi Jun,Ye Jing,Zhuang Xu,Cheng Xiaoyue,Fu Ruojin,Zhao Aimin
The journal of obstetrics and gynaecology research
AIM:Venous thromboembolism (VTE) is a major cause of morbidity and mortality in gynecologic malignant patients after surgery. We aimed to validate the Caprini risk assessment model (RAM) and elevated tumor-specific D-dimer as predictive marker of postoperative VTE for patients undergoing surgery of gynecologic malignancies. METHODS:Inpatients were divided into five groups (low: score = 0-1; moderate: score = 2; high: score = 3-4; higher: score = 5-7; sup-high: score > 7) and treated according to their risk level after the surgery during the hospitalization according to the Caprini RAM. D-dimer level was detected during the perioperative period. If D-dimer did not fall to normal reference range on the seventh day after operation, the use of low-molecular-weight heparin was prolonged to 28 days after surgery. RESULTS:The majority (853/974, 87.6%) of the patients was in the Caprini score ≥5, with an overall VTE incidence of 1.75%. The VTE group had significantly higher Caprini score, CA125, vascular invasion rate and lymph node metastasis rate. If 1.5 μg/mL was used as the D-dimer cut-off value to predicting VTE, the sensitivity was 87.5%, the specificity was 93.8% and the negative predictive value was 99.2%. The D-dimer level was a marker for prolonging the anticoagulants use during the perioperative period, especially for the sup-high group. CONCLUSION:The Caprini RAM is an effective and reliable VTE risk prediction tool for patients undergoing gynecological malignant tumor surgery. The group (score ≥ 5) can be divided into two subgroups (higher: score = 5-7 and sup-high: score > 7), which may better predict the occurrence of VTE for malignant tumor patients. Great than 1.5 μg/mL D-dimer before operation should be given more attention for the presence of VTE.
[Advances of mediastinal lymph node metastasis and the extent of lymph node
dissection in patients with stage T1 non-small cell lung cancer].
Ding Ningning,Mao Yousheng
Zhongguo fei ai za zhi = Chinese journal of lung cancer
Lung cancer ranks the first position in morbidity and mortality among all malignances in China. Non-small cell lung cancer (NSCLC) accounts for nearly 80% of all lung malignancies. Surgical resection is still the current major treatment method for early stage NSCLC. Lymph node stages together with the extent of lymph node dissection directly affect the prognosis. The site of primary lung carcinoma may affect the route and status of lymph node metastasis. Up to now, anatomical lobectomy and mediastinal lymph node dissection is deemed to be the standard surgical treatment for NSCLC. However, it is still controversial in the extent of lymph node dissection for T1 NSCLC. More and more surgeons intend to perform selective mediastinal lymph node dissection instead of complete mediastinal lymph node dissection for T1 NSCLC in recent years.
[Correlation between baseline plasma D-dimer levels and prognosis in patients with non-smal cell lung cancer].
Zhang Ping-ping,Sun Jun-wei,Lu Jiu-qin,Ma Liang-liang,Li Kai
Zhonghua zhong liu za zhi [Chinese journal of oncology]
OBJECTIVE:To investigate the correlation of baseline plasma D-dimer levels and clinicopathological features and tumor VEGF expression in non-small cell lung cancer(NSCLC) patients, and to evaluate the value of D-dimer in predicting survival time. METHODS:A retrospective review of the clinicopathological data of 290 NSCLC patients confirmed pathologically in Tianjin Cancer Hospital from July 2007 to April 2009 was performed. The correlations between plasma baseline D-dimer levels and clinicopathological characteristics and progonosis were analyzed. RESULTS:For 290 NSCLC patients with low ( ≤ 0.3 µg/ml) and high (>0.3 µg/ml) D-dimer levels, the median survival times were 54.0 months and 46.2 months, respectively (P < 0.05), and for the patients with stages I, II, IIIA, IIIB and IV NSCLC, the median survival times were 58.1, 40.6, 26.7 and 23.5 months, respectively (P < 0.05). In the operable patients (stages I, II and IIIa) with low and high D-dimer levels, the median progression-free survivals (PFS) were 35.0 and 11.0 months, respectively (P < 0.05). Furthermore, the median PFSs were 57.2 months and 19.6 months, respectively, in these operable patients without and with lymph node metastasis (P < 0.05). CONCLUSIONS:High levels of baseline plasma D-dimer may indicate advanced disease stage, larger tumor size, lymph node metastasis and stronger tumor angiongenesis to some extent, and may be useful in prediction of survival time in NSCLC patients of different stages.
Plasma D-dimer value as a predictor of malignant lymph node involvement in operable non-small cell lung cancer.
Chen Feng,Wang Min-Jie,Li Jia,Yan Cui-E,Han Xiao-Hong,Wu Zong-Yong,Qi Jun
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
Fibrin deposition and remodelling of the extracellular matrix are important early steps in tumour metastasis. The D-dimer value is an indicator of intravascular fibrin formation and degradation. Thus, the D-dimer value may be a predictor of the malignant involvement of lymph nodes in operable non-small cell lung cancer (NSCLC) patients. The study comprised 142 highly suspected lung cancer patients scheduled to undergo pneumonectomy, lobectomy or wedge resection. Of the 142 patients, 124 were subsequently diagnosed as NSCLC, and 18 were subsequently diagnosed as benign lung disease by histological examination. Preoperative plasma D-dimer values were quantified, and the relationship between plasma D-dimer and clinical variables including tumour size, involvement of lymph nodes and clinical stage was examined using Spearman correlation coefficients and χ (2) tests. The median plasma D-dimer values were statistically higher in NSCLC patients with malignant lymph nodes than in those who suffered either benign lung disease or carcinoma in situ (Kruskal-Wallis test; P = 0.001). Plasma D-dimer values were significantly correlated with clinical stage (ANOVA; P = 0.009). An obvious relationship was observed between elevated D-dimer (>0.475 mg/L fibrinogen equivalent units) and malignant lymph node involvement (χ (2) test; P = 0.0000). This correlation suggests that the plasma D-dimer value is a clinically important predictor for the malignant involvement of lymph nodes in operable NSCLC.
[Correlation between Plasma D-dimer Count and Features of
Non-small Cell Lung Cancer].
Song Xu,Wang Fengmin,Shen Haibo,Li Jie,Hu Tianjun,Yang Zhenhua,Zhou Yinjie,Shi Qiang
Zhongguo fei ai za zhi = Chinese journal of lung cancer
BACKGROUND:More and more patients with small pulmonary nodules (SPN) can be found along with the developing of chest low-dose computed tomography (LDCT). With current examinations not all the SPN can be diagnosed to be benign or malignant and not all the malignant nodules can be diagnosed to be lymphatic metastasis. We need to study the correlation between plasma D-dimer count of patients before surgery with pathology features of non-small cell lung cancer (NSCLC). METHODS:The study comprised 567 highly suspected lung cancer patients. Preoperative plasma D-dimer were qualified, and the relationship between plasma D-dimer with pathology features including benign or malignant nodules, tumor size and involvement of lymph nodes was examined using Kruskal-Wallis test and Spearman correlation coefficients. RESULTS:The median plasma D-dimer values were statistically higher in NSCLC patients than in those who suffered from benign lung nodules (P<0.001). The median plasma D-dimer values in NSCLC patients with malignant lymph nodes were statistically higher than in those without malignant lymph nodes (P<0.001). An obvious relationship was observed between elevated D-dimer with number of malignant lymph nodes involvement and tumer size. An obvious relationship was observed between elevated D-dimer (>112.5 ng/mL) and malignant lymph node involvement in stage T1 lung cancer. CONCLUSIONS:The plasma D-dimer maybe useful for early diagnosis, staging and prognosis of the patients with NSCLC. The plasma D-dimer can be one of the indicator to identify what kind of patients need mediastinal lymph node cleaning.
[Harmonization of cut-off values of commercially available D-dimer tests].
Török-Nagy Beáta,Vajda Zoltán,Vásárhelyi Barna
INTRODUCTION:The objective of the D-dimer tests is to exclude venous thromboembolic disorders. The characteristics of various D-dimer tests differ significantly and consequently, their results are difficult to compare. AIM:Our goal was to compare three D-dimer tests, analyse their correlation and harmonise their sensitivity and specificity through the optimisation of cut-off values. METHOD:At Semmelweis University, the D-dimer level was determined with three different reagents in 158 plasma samples, suspected with venous thromboembolism. INNOVANCE D-Dimer was selected as the referent, and in the case of the two other tests (STA-Liatest D-Di; Dia-D-Dimer), the cut-off values were changed between 0.2-1 µg/ml (fibrinogen-equivalent unit - FEU). The optimal cut-off values were estimated by diagnostic parameters and chi-square test. The correlation of the different tests was calculated by regression analysis. RESULTS:Based on the chi-square statistics, there is no significant difference between STA-Liatest D-Di and INNOVANCE D-Dimer tests using the cut-off values 0.3-1 µg/ml (FEU) (STA-Liatest D-Di). In the case of Dia-D-DIMER, there is a significant difference using 0.2-0.3 µg/ml (FEU) cut-off values, 0.4 µg/ml (FEU) is a border-line value and using 0.5-1 µg/ml (FEU) cut-off values, there is no significant difference. The sensitivity of STA-Liatest D-Di changed between 82.7-100% using 0.2-1 µg/ml (FEU) cut-off values, while the sensitivity of Dia-D-DIMER was 92.3-100%. Their specificities ranged between 50-96.3% and 35.2-87%. The optimal cut-off values were estimated as 0.5-0.6 µg/ml (FEU) for the STA-Liatest D-Di test and 0.7 µg/ml (FEU) for the Dia-D-DIMER test. CONCLUSION:Each diagnostic laboratory should determine the optimal cut-off value of the D-dimer test in use, considering the examined population of the area. Orv Hetil. 2019; 160(15): 585-592.
Combination of Preoperative D-Dimer and Platelet Distributionwidth Predicts Postoperative Deep Venous Thrombosis inPatients with Cervical Carcinoma
Li Na,Zhang Fu-Bin,Li Bing-Jie,Wang Rui-Tao
Asian Pacific journal of cancer prevention : APJCP
Background: Deep venous thrombosis (DVT) is associated with severe morbidity and mortality in cancer. Plateletdistribution width (PDW), a platelet index, indicates variation in platelet size. We aimed to investigate whether thecombination of D-dimer and PDW could have a better performance in predicting DVT in patients with cervicalcarcinoma. Materials and Methods: In 198 consecutive cervical carcinoma patients without preoperative DVT,preoperative D-dimer and PDW levels were measured. Compression ultrasonography was performed in all cervicalcarcinoma patients before surgery, as well as one month, three months, six months, and 12 months. Results: During amedian period of 12 months, 17 of the 198 patients (8.6 %) developed DVT. PDW levels were reduced and D-dimerlevels were increased in patients with DVT events compared to those without DVT. Multivariate Cox analysis revealedthat both PDW and D-dimer were independent predictors for DVT events. The area under the ROC curve was 0.628(95% CI: 0.556 to 0.695, p=0.142) when D-dimer was used alone, whereas it increased to 0.777 (95% CI: 0.712 to0.833, p<0.011) with the addition of PDW. Incorporation of PDW into the D-dimer model significantly improved thepredictive value. Conclusions: The combination of preoperative D-dimer and PDW improves the predictive power ofpostoperative DVT risk in patients with cervical carcinoma.
D-Dimer level was associated with prognosis in metastatic colorectal cancer: A Chinese patients based cohort study.
Liu Chan,Ning Yueguo,Chen Xiaoming,Zhu Qian
D-dimer level is a direct measure of activated coagulation and has been used as a biomarker of hypercoagulability. In this study, we aimed to explore the associations between D-dimer level and the clinicopathological features and prognosis in metastatic colorectal cancer (mCRC) patients. One hundred seventy-eight patients diagnosed with mCRC from the Department of General Surgery, Jingmen First People's Hospital from September 2014 to December 2018 were collected. Data of coagulation index was evaluated and survival analysis was performed to identify the biomarker of mCRC. Among 178 cases of colorectal cancer, we found that the value of 0.55 mg/L, 5ng/ml and 40U/ml were cut-off values of D-Dimer, CEA and CA-199 for patients survival, respectively. hypercoagulability was much more frequent in patients aged ≥60 years than <60 years (P < .001) and also in patients with ECOG ≥2 points (P < .001). Moreover, those patients who have CEA >5ng/ml and CA-199>40U/ml had hypercoagulable state (P < .001). There was a significant difference in D-Dimer >0.55 mg/L and D-Dimer ≤0.55 mg/L among the number of metastatic sites (P < .01) and patients with comorbidities (P < .01). Survival analysis showed that patients with D-Dimer >0.55 mg/L have significantly unfavorable overall survival (P = .006) and progressive free survival (P = .011).
D-dimer increase: an unfavorable factor for patients with primary liver cancer treated with TACE.
Chen Xujiao,Chang Zhihui,Liu Zhaoyu
Cancer chemotherapy and pharmacology
PURPOSE:To explore the clinical significance of plasma D-dimer increase for transcatheter arterial chemoembolization (TACE) in patients with primary liver cancer (PLC). METHODS:The clinical data of 80 PLC patients who underwent TACE in our hospital from January 2015 to January 2017 were collected, including the plasma D-dimer level 1 week before TACE (D0), D-dimer level 1 month after TACE (D1) and D-dimer level when the disease begins to progress (D2). 1 Month after TACE, these patients were divided into two groups according to the mRecist criteria: disease-controlled group (CR + PR + SD) and disease-progressing group (PD). In all subjects, progression-free survival (PFS) was recorded. D0 and D1 were compared between the two groups by the rank sum test; and the relation between D-dimer level and PFS was assessed by the Kaplan-Meier test and Breslow test. RESULTS:In the disease-controlled group, there was no significant difference between D0 and D1 (P > 0.05); in the disease-progressing group, D1 was significantly higher than D0 (P < 0.05) and the D1 is higher than that in disease-controlled group. In the patients with a negative D1 or D2, PFS was longer than those with a positive level (both P < 0.05), but such difference was not statistically significant in D0 (P > 0.05). In the patients with a D-dimer level increase after TACE (group 3), PFS was shorter than that in those with a D-dimer level decrease after TACE (Group 1) and that in those with a relatively stable D-dimer level before and after TACE (Group 2) (P < 0.05); survival in Group 1 was slightly but not significantly longer than that in Group 2 (P > 0.05). CONCLUSION:The change in plasma D-dimer level can be used as a biological index to assess the efficacy of TACE and prognosis for PLC patients, and thus, a positive D-dimer level or D-dimer increase after TACE is an unfavorable factor.
The value of FDP/FIB and D-dimer/FIB ratios in predicting high-risk APL-related thrombosis.
Bai Yanliang,Shi Mingyue,Yang Xiawan,Zhang Wanjun,Yang Ruyu,Wei Xiuli,Wei Xudong,Duan Lijuan,Wang Chenghua,Mi Ruihua,Waqas Ahmed Hafiz Abdul,Huo Lei,Chen Yuqing,Xu Fangfang,Wu Depei,Sun Kai
Hemorrhage is the typical manifestation of APL-related coagulopathy while thrombosis is infrequently reported. In a retrospective analysis with 33 patients with hyperleukocytic APL, we found 6 out of 33 hyperleukocytic APL patients presented with thrombosis rather than hemorrhage. A notable feature in these high-risk APL patients with thrombosis is that there were no significant abnormalities in fibrinogen (FIB), prothrombin time (PT) and activated partial thromboplastin time (APTT). Compared with the normal ranges, both the high-risk APL patients with thrombosis and the high-risk APL patients with hemorrhage had a significant increase in fibrinogen degradation product (FDP) and d-dimer levels. However, the group with hemorrhage had noticeably higher plasma levels of FDP and d-dimer than the group with thrombosis. To find a close relationship between coagulation markers and the onset of thrombotic events in patients with high-risk APL, the potential effects of FDP/FIB and d-dimer/FIB ratios as risk markers were investigated. We demonstrated that FDP/FIB and d-dimer/FIB ratios in the patients with high-risk APL with thrombosis showed higher ratios than the normal range but significantly lower ratios than the patients with high-risk APL-related hemorrhage. Our data demonstrated that the alteration in FDP/FIB and d-dimer/FIB ratios have more significant relevance than the levels of FIB, FDP or d-dimer as potential factors for predicting thrombosis and may help with designing more appropriately risk-adapted treatment protocols or personalized therapy.
Comorbidity burden conditions the prognostic performance of D-dimer in elderly patients with acute pulmonary embolism.
Polo Friz Hernan,Pezzetti Valentina,Orenti Annalisa,Caleffi Alessandro,Corno Valeria,Crivellari Chiara,Petri Francesco,Polo Friz Melisa,Punzi Veronica,Teruzzi Daniela,d'Oro Luca Cavalieri,Giannattasio Cristina,Vighi Giuseppe,Cimminiello Claudio,Boracchi Patrizia
The American journal of emergency medicine
INTRODUCTION:The prognostic accuracy of D-dimer for risk assessment in acute Pulmonary Embolism (APE) patients may be hampered by comorbidities. We investigated the impact of comorbidity burden (CB) by using the Charlson Comorbidity Index (CCI), on the prognostic ability of D-dimer to predict 30 and 90-day mortality in hemodynamically stable elderly patients with APE. METHODS:All patients aged >65 years with normotensive APE, consecutively evaluated in the Emergency Department since 2010 through 2014 were included in this retrospective cohort study. Area under the curve (AUC) and ½ Net Reclassification Improvement (NRI) were calculated. RESULTS:Study population: 162 patients, median age: 79.2 years. The optimal cut-off value of CCI score for predicting mortality was ≤1 (Low CB) and >1 (High CB), AUC = 0.786. Higher levels of D-dimer were associated with an increased risk death at 30 (HR = 1.039, 95%CI:1.000-1.080, p = 0.049) and 90 days (HR = 1.039, 95%CI:1.009-1.070, p = 0.012). When added to simplified Pulmonary Embolism Severity Index (sPESI) score, D-dimer increased significantly the AUC for predicting 30-day mortality in Low CB (AUC = 0.778, 95%CI:0.620-0.937, ½NRI = 0.535, p = 0.015), but not in High CB patients (AUC = 0.634, 95%CI:0.460-0.807, ½ NRI = 0.248, p = 0.294). Similarly, for 90-day mortality D-dimer increased significantly the AUC in Low CB (AUC = 0.786, 95%CI:0.643-0.929, ½NRI = 0.424, p-value = 0.025), but not in High CB patients (AUC = 0.659, 95%CI:0.541-0.778, ½NRI = 0.354, p-value = 0.165). CONCLUSION:In elderly patients with normotensive APE, comorbidities condition the prognostic performance of D-dimer, which was found to be a better predictor of death in subjects with low CB. These results support multimarker strategies for risk assessment in this population.
Comparison of the age-adjusted and clinical probability-adjusted D-dimer to exclude pulmonary embolism in the ED.
Sharif Sameer,Eventov Michelle,Kearon Clive,Parpia Sameer,Li Meirui,Jiang River,Sneath Paula,Fuentes Carmen Otero,Marriott Christopher,de Wit Kerstin
The American journal of emergency medicine
BACKGROUND:Diagnosing pulmonary embolism (PE) in the emergency department (ED) can be challenging because its signs and symptoms are non-specific. OBJECTIVE:We compared the efficacy and safety of using age-adjusted D-dimer interpretation, clinical probability-adjusted D-dimer interpretation and standard D-dimer approach to exclude PE in ED patients. DESIGN/METHODS:We performed a health records review at two emergency departments over a two-year period. We reviewed all cases where patients had a D-dimer ordered to test for PE or underwent CT or VQ scanning for PE. PE was considered to be present during the emergency department visit if PE was diagnosed on CT or VQ (subsegmental level or above), or if the patient was subsequently found to have PE or deep vein thrombosis during the next 30 days. We applied the three D-dimer approaches to the low and moderate probability patients. The primary outcome was exclusion of PE with each rule. Secondary objective was to estimate the negative predictive value (NPV) for each rule. RESULTS:1163 emergency patients were tested for PE and 1075 patients were eligible for inclusion in our analysis. PE was excluded in 70.4% (95% CI 67.6-73.0%), 80.3% (95% CI 77.9-82.6%) and 68.9%; (95% CI 65.7-71.3%) with the age-adjusted, clinical probability-adjusted and standard D-dimer approach. The NPVs were 99.7% (95% CI 99.0-99.9%), 99.1% (95% CI 98.3-99.5%) and 100% (95% CI 99.4-100.0%) respectively. CONCLUSION:The clinical probability-adjusted rule appears to exclude PE in a greater proportion of patients, with a very small reduction in the negative predictive value.
Comparison of Wells and YEARS clinical decision rules with D-dimer for low-risk pulmonary embolus patients.
McLenachan Christopher J,Chua Olivia,Chan Betty S H,Vecellio Elia,Chiew Angela L
Internal medicine journal
BACKGROUND:Assessment of pulmonary embolism (PE) remains a diagnostic and investigative burden to emergency departments. The decision of which D-dimer cut-off to use in low-risk patients remains controversial. AIMS:To compare the sensitivity and specificity of varying D-dimer cut-offs in the diagnosis of PE for Wells low-risk patients. METHODS:Retrospective review of patients presenting to a tertiary emergency department over 42 months who had a D-dimer performed for PE risk stratification. Wells scores were calculated for each patient, those with Wells score of ≤4 ('PE unlikely') were analysed. Four D-dimer thresholds were compared, including traditional threshold (≥0.5 μg/mL), age-adjusted (≥age in years × 0.01 μg/mL), doubled-traditional threshold and YEARS criteria. RESULTS:During the study period, 2291 D-dimers were ordered for suspected PE, of which 2125 were low risk for PE. Of these low-risk patients 46 (2.2%) were found to have a PE. The sensitivity and specificity for each D-dimer threshold were traditional threshold (95.6% and 65.6%), age-adjusted (93.5% and 71.7%), doubled traditional (69.6% and 85.5%) and YEARS criteria (80.4% and 84.0%). Utilising an age-adjusted threshold, YEARS criteria or doubled-traditional threshold would have resulted in 70, 217 and 245 fewer imaging investigations. CONCLUSIONS:The prevalence of PE in this low-risk cohort was very low. Utilising an age-adjusted D-dimer would have reduced imaging tests performed while maintaining good sensitivity. Although The YEARS criteria and doubled-traditional threshold would have reduced scanning considerably both had sensitivities of less than 90%.
Development and validation of a model that includes two ultrasound parameters and the plasma D-dimer level for predicting malignancy in adnexal masses: an observational study.
Stukan Maciej,Badocha Michał,Ratajczak Karol
BACKGROUND:Pre-operative discrimination of malignant from benign adnexal masses is crucial for planning additional imaging, preparation, surgery and postoperative care. This study aimed to define key ultrasound and clinical variables and develop a predictive model for calculating preoperative ovarian tumor malignancy risk in a gynecologic oncology referral center. We compared our model to a subjective ultrasound assessment (SUA) method and previously described models. METHODS:This prospective, single-center observational study included consecutive patients. We collected systematic ultrasound and clinical data, including cancer antigen 125, D-dimer (DD) levels and platelet count. Histological examinations served as the reference standard. We performed univariate and multivariate regressions, and Bayesian information criterion (BIC) to assess the optimal model. Data were split into 2 subsets: training, for model development (190 observations) and testing, for model validation (n = 100). RESULTS:Among 290 patients, 52% had malignant disease, including epithelial ovarian cancer (72.8%), metastatic disease (14.5%), borderline tumors (6.6%), and non-epithelial malignancies (4.6%). Significant variables were included into a multivariate analysis. The optimal model, included three independent factors: solid areas, the color score, and the DD level. Malignant and benign lesions had mean DD values of 2.837 and 0.354 μg/ml, respectively. We transformed established formulae into a web-based calculator ( http://gin-onc-calculators.com/gynonc.php ) for calculating the adnexal mass malignancy risk. The areas under the curve (AUCs) for models compared in the testing set were: our model (0.977), Simple Rules risk calculation (0.976), Assessment of Different NEoplasias in the adneXa (ADNEX) (0.972), Logistic Regression 2 (LR2) (0.969), Risk of Malignancy Index (RMI) 4 (0.932), SUA (0.930), and RMI3 (0.912). CONCLUSIONS:Two simple ultrasound predictors and the DD level (also included in a mathematical model), when used by gynecologist oncologist, discriminated malignant from benign ovarian lesions as well or better than other more complex models and the SUA method. These parameters (and the model) may be clinically useful for planning adequate management in the cancer center. The model needs substantial validation.
Investigation of age-adjusted D-dimer using an uncommon assay.
Parks Christopher,Bounds Richard,Davis Barbara,Caplan Richard,Laughery Tom,Zeserson Eli
The American journal of emergency medicine
BACKGROUND:Use of an age-adjusted D-dimer for the evaluation of acute pulmonary embolus (PE) has been prospectively validated in the literature and has become a practice recommendation from major medical societies. Most research on this subject involves the most common D-dimer assays reporting in Fibrinogen Equivalent Units (FEU) with a non-age-adjusted manufacturer-recommended cutoff of 500 ng/ml FEU. Limited research to date has evaluated age-adjustment in assays that report in D-Dimer Units (D-DU), which use a manufacturer-recommended cutoff of 230 ng/ml D-DU. Despite scant evidence, an age-adjusted formula using D-DU has been recently endorsed by the American College of Emergency Physicians (ACEP). This formula seems arbitrary in its derivation and unnecessarily deviates from existing thresholds, thus prompting the creation of our novel-age adjustment formula. The goal of this study was to retrospectively evaluate the test characteristics of our novel age-adjusted D-dimer formula using the D-DU assay in comparison to existing traditional and age-adjusted D-dimer thresholds for the evaluation of acute PE in the ED. METHODS:This was a retrospective chart review at an academic quaternary health system with three EDs and 195,000 combined annual ED visits. Only patients with D-dimer testing and CT PE protocol (CTPE) imaging were included. Admission and discharge diagnosis codes were used to identify acute PE. Outcome measures were sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of an unadjusted traditional threshold (230) compared with both novel and ACEP-endorsed age adjusted thresholds, (Age × 5) - 20 and Age × 5 if >50, respectively. Estimates with their exact 95% threshold were performed. RESULTS:4846 adult patients were evaluated from January 2012 to July 2017. Group characteristics include a mean age of 52 and a frequency of acute PE diagnosis by CTPE of 8.25%. Traditional D-dimer cutoff demonstrated a sensitivity of 99.8% (95% CI 98.6-100), specificity of 16.7% (95% CI 15.6-17.8) and NPV of 99.9% (95% CI 99.3-100). Our novel age-adjusted D-dimer thresholds had a sensitivity of 97.0% (95% CI 94.8-98.4), specificity of 27.9% (95% CI 26.6-29.2) and NPV of 99.0% (95% CI 98.3-99.5) with the ACEP-endorsed formula demonstrating similar test characteristics. CONCLUSION:Use of an age-adjusted D-dimer on appropriately selected patients being evaluated for acute PE in the ED with a D-DU assay increases specificity while maintaining a high sensitivity and NPV. Both our novel formula and the ACEP-endorsed age-adjusted formula performed well, with our novel formula showing a trend towards improved testing characteristics.
Patient-level meta-analysis: effect of measurement timing, threshold, and patient age on ability of D-dimer testing to assess recurrence risk after unprovoked venous thromboembolism.
Douketis James,Tosetto Alberto,Marcucci Maura,Baglin Trevor,Cushman Mary,Eichinger Sabine,Palareti Gualtiero,Poli Daniela,Tait R Campbell,Iorio Alfonso
Annals of internal medicine
BACKGROUND:In patients with a first unprovoked venous thromboembolism (VTE), an elevated d-dimer level after anticoagulation is stopped is a risk factor for recurrent VTE. However, questions remain about the utility of measuring d-dimer in clinical practice. PURPOSE:To determine whether the timing of testing, patient age, and the cut point used to define a positive or negative result affect the ability of d-dimer testing to distinguish risk for recurrent disease. DATA SOURCES:Comprehensive search of electronic databases (MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials) until July 2010, supplemented by reviewing conference abstracts and contacting content experts. STUDY SELECTION:7 prospective studies that investigated an association between d-dimer, measured after stopping anticoagulation, and disease recurrence in patients with a first unprovoked VTE (proximal deep venous thrombosis, pulmonary embolism, or both). DATA EXTRACTION:Patient-level databases were obtained, transferred to a central database, checked, completed with further information provided by study investigators, and pooled into a single database. DATA SYNTHESIS:1818 patients with a first unprovoked VTE were followed for a mean of 26.9 months (SD, 19.1). A study-stratified multivariate Cox regression model, which included patient age, sex, hormone therapy use at the time of the index event, body mass index, timing of postanticoagulation d-dimer testing, and inherited thrombophilia as possible confounders, indicated that the hazard ratio for d-dimer status (positive vs. negative) was 2.59 (95% CI, 1.90 to 3.52). Only male sex had a significant effect on risk for recurrent VTE independent of d-dimer status. The Cox regression model and the log-rank test confirmed that the risk for recurrent VTE was higher in patients with a positive d-dimer result than in those with a negative result, regardless of the timing of postanticoagulation d-dimer testing or patient age. No study- or assay-specific d-dimer effect was found, and reassessing the analysis after recoding data according to specific quantitative d-dimer cut points (500 µg/L and 250 µg/L) did not change the results. LIMITATIONS:Unmeasured variables could have affected the risk for recurrent VTE. The study population was predominantly white. CONCLUSION:In patients with a first unprovoked VTE who have their d-dimer level measured after stopping anticoagulation, the timing of d-dimer testing, patient age, and the assay cut point used do not affect the ability of d-dimer to distinguish patients with a higher or lower risk for recurrent VTE.
Age-adjusted D-dimer cut-off leads to more efficient diagnosis of venous thromboembolism in the emergency department: a comparison of four assays.
Farm M,Siddiqui A J,Onelöv L,Järnberg I,Eintrei J,Maskovic F,Kallner A,Holmström M,Antovic J P
Journal of thrombosis and haemostasis : JTH
Essentials Age-adjusted D-dimer cut-offs decrease the false positives in the elderly. Four D-dimer assays were compared in venous thromboembolism outpatients in an emergency ward. Age-adjusted cut-off resulted in improved specificity with maintained sensitivity for all assays. There was a substantial decrease in false positive results, especially in the older population. SUMMARY:Background The study compares different D-dimer assays and age-adjusted cut-offs in outpatients with suspected venous thromboembolism (VTE). The plasma concentration of this sensitive biomarker is increased by activated coagulation, but also by several conditions that are linked to an increased risk of VTE. One such condition is old age, which poses a common clinical problem where many prefer not to analyze D-dimer in elderly patients. Age-adjusted cut-offs have been validated for both deep venous thrombosis (DVT) and pulmonary embolism, aiming to increase specificity without notably decreasing sensitivity. Objectives We evaluated four common D-dimer assays in parallel, with and without applying age-adjusted cut offs for VTE. Patients/methods The prospective single-center study was conducted in 940 outpatients attending the emergency department with clinically suspected pulmonary embolism or DVT. Four automated D-dimer assays were compared (Siemens INNOVANCE , Roche Tina-quant, Medirox MRX and STA -Liatest D-Di PLUS). Results All assays performed with areas under the ROC curve (AUC) > 0.9 and maintained their sensitivities after implementation of age-adjusted cut-offs. Specificities increased by 6-7% and number needed to test decreased by < 0.3. The rate of false positive results decreased by 6% overall and by 10-20% for patients ≥ 70. Conclusions Age-adjusted cut-offs resulted in maintained high sensitivity and a modest improvement in specificity and number needed to test for all evaluated D-dimer assays. There was a significant reduction in false positive results, which reflects avoidable unnecessary imaging without any compromise of clinical safety. This suggests a potential to benefit the management of VTE in elderly patients, both clinically and economically.
Comparison of clinical probability-adjusted D-dimer and age-adjusted D-dimer interpretation to exclude venous thromboembolism.
Takach Lapner Sarah,Julian Jim A,Linkins Lori-Ann,Bates Shannon,Kearon Clive
Thrombosis and haemostasis
Two new strategies for interpreting D-dimer results have been proposed: i) using a progressively higher D-dimer threshold with increasing age (age-adjusted strategy) and ii) using a D-dimer threshold in patients with low clinical probability that is twice the threshold used in patients with moderate clinical probability (clinical probability-adjusted strategy). Our objective was to compare the diagnostic accuracy of age-adjusted and clinical probability-adjusted D-dimer interpretation in patients with a low or moderate clinical probability of venous thromboembolism (VTE). We performed a retrospective analysis of clinical data and blood samples from two prospective studies. We compared the negative predictive value (NPV) for VTE, and the proportion of patients with a negative D-dimer result, using two D-dimer interpretation strategies: the age-adjusted strategy, which uses a progressively higher D-dimer threshold with increasing age over 50 years (age in years × 10 µg/L FEU); and the clinical probability-adjusted strategy which uses a D-dimer threshold of 1000 µg/L FEU in patients with low clinical probability and 500 µg/L FEU in patients with moderate clinical probability. A total of 1649 outpatients with low or moderate clinical probability for a first suspected deep vein thrombosis or pulmonary embolism were included. The NPV of both the clinical probability-adjusted strategy (99.7 %) and the age-adjusted strategy (99.6 %) were similar. However, the proportion of patients with a negative result was greater with the clinical probability-adjusted strategy (56.1 % vs, 50.9 %; difference 5.2 %; 95 % CI 3.5 % to 6.8 %). These findings suggest that clinical probability-adjusted D-dimer interpretation is a better way of interpreting D-dimer results compared to age-adjusted interpretation.
D-dimer at venous thrombosis diagnosis is associated with risk of recurrence.
Bjøri E,Johnsen H S,Hansen J-B,Braekkan S K
Journal of thrombosis and haemostasis : JTH
Essentials Whether D-dimer at incident venous thromboembolism (VTE) can predict recurrence-risk is unknown. We explored this association in 454 cancer-free patients with a first lifetime VTE. A low D-dimer at first VTE diagnosis was associated with a low recurrence risk. The association was predominant in patients with deep vein thrombosis and unprovoked VTE. Click to hear Dr Cannegieter's presentation on venous thrombosis: prediction of recurrence SUMMARY: Background Venous thromboembolism (VTE) is a common disease with a high recurrence rate. D-dimer measured after cessation of anticoagulant therapy predicts recurrence, and is used to decide on treatment prolongation. However, whether D-dimer measured at first VTE diagnosis can be used to assess recurrence-risk is unknown. Aims To investigate the association between D-dimer, measured at first VTE diagnosis and risk of recurrent VTE. Methods Information on clinical risk factors and laboratory markers were collected in 454 cancer-free patients with a first VTE. Recurrent VTEs and deaths during follow-up (1994-2012) were recorded. Results During a median follow-up of 3.9 years, 84 patients experienced a recurrent VTE. The crude recurrence rate was 1.7 (95% confidence interval [CI], 1.0-2.9) per 100 person-years in the lower quartile of D-dimer (≤ 1500 ng mL ), and 4.9 (95% CI, 3.9-6.1) per 100 person-years in the upper three quartiles combined, yielding an absolute risk difference of 3.2 per 100 person-years. Patients with D-dimer ≤ 1500 ng mL had 54% lower recurrence-risk than patients with D-dimer > 1500 ng mL (HR, 0.46; 95% CI, 0.25-0.82). The association was particularly pronounced among patients with unprovoked events and deep vein thrombosis, showing a 66% (HR, 0.34; 95% CI, 0.15-0.74) and 68% (HR, 0.32; 95% CI, 0.14-0.71) lower recurrence risk among patients with D-dimer ≤ 1500 ng mL , respectively. Conclusions A low D-dimer (≤ 1500 ng mL ) measured at first VTE diagnosis was associated with a low recurrence risk, particularly among patients with DVT and unprovoked events. Our findings suggest that a clinical decision to avoid prolonged anticoagulant treatment could be considered based on low D-dimer at the time of VTE diagnosis.
Plasma D-dimer as a predictor of intraluminal thrombus burden and progression of abdominal aortic aneurysm.
Fan Ying-Nan,Ke Xiao,Yi Zhi-Long,Lin Yong-Qing,Deng Bing-Qing,Shu Xiao-Rong,Yang Da-Hao,Liao Zhi-Yong,Nie Ru-Qiong
AIM:Intraluminal thrombus (ILT) is presented in most abdominal aortic aneurysms (AAAs) and is suggested to promote AAA expansion. D-dimer, a breakdown product in the thrombus remodeling, may have prognostic value for AAA. This study investigated the interrelation between plasma D-dimer level, ILT volume, AAA size and progression. MAIN METHODS:This was a retrospective observational study that involved 181 patients with infra-renal AAA. They were divided into small and large AAA groups according to AAA diameter. 24 of them had repeated abdominal computed tomography angiography (CTA) scan and were divided into slow-growing and fast-growing AAA groups according to the median value of AAA growth rate. Baseline and follow-up plasma D-dimer level, maximum diameter of AAA, total infra-renal aortic volume and ILT volume were analyzed. KEY FINDINGS:Plasma D-dimer level was positively correlated with ILT volume (R = 0.382, P < 0.001) and maximum diameter of AAA (R = 0.442, P < 0.001). Increasing value of plasma D-dimer was positively associated with the accelerated growth rate of AAA (R = 0.720, P < 0.01). ILT volume showed positive correlation with maximum diameter (R = 0.859, P < 0.001) and growth rate of AAA (R = 0.490, P < 0.05). After adjusting the baseline ILT volume, the positive correlations remained to be statistically significant between plasma D-dimer level and AAA size (R = 0.200, P < 0.05), as well as increasing value of plasma D-dimer and growth rate of AAA (R = 0.642, P < 0.05). SIGNIFICANCE:Plasma D-dimer level reflected ILT burden in AAAs. Plasma D-dimer level and ILT volume were positively correlated with AAA size. Increasing value of plasma D-dimer and baseline ILT volume could be predictors of AAA progression.
Cerebral venous and sinus thrombosis diagnosis: preliminary study of clinical picture and D-dimer concentration correlation.
Neurologia i neurochirurgia polska
AIM OF THE STUDY:We investigated whether D-dimer (DD) concentration is elevated in cerebral venous and sinus thrombosis (CVST), as has been reported in the literature. CLINICAL RATIONALE FOR THE STUDY:CVST is a disease with variable clinical presentations and a challenging diagnosis. We looked into whether D-dimer concentration might be an indicator of CVST, and the need for neuroimaging tests correlated with clinical factors. MATERIALS AND METHODS:We included all consecutive patients (mean age 41.6 years) with CVST treated in our neurology department from 2014 to 2018 whose DD levels had been measured. DD concentrations were categorised as normal (≤ 0.5 μg/ml) or elevated ( > 0.5 μg/ml). Appropriate imaging confirmed the diagnosis of CVST. The results were compared to those of a control group consisting of 22 age- and sex-matched patients (mean age 40 years) with a diagnosis of primary headache (tension type or migraine) hospitalised to exclude secondary causes. RESULTS:In 20 patients in the CVST study group, median level of DD was 1.0 + 0.57 μg/ml (range 0.19-2.45 μg/ml), compared to the control group's mean DD level of 0.50 + 0.45 μg/ml (range 0.15-1.73 μg/ml), with p < 0.005. Higher DD levels were associated with complications of the disease and fatal course (p < 0.005). One female and one male patient died because of CVST with DD levels of (respectively) 2.45 and 1.80 μg/ml - the two highest concentrations in our study group. CONCLUSIONS AND CLINICAL IMPLICATIONS:DD concentration, especially in headache patients, may be a factor to predict CVST and an indicator for further diagnostic procedures with venography. But in clinical practice, low levels of DD cannot be taken to exclude CVST.
D-dimer and C-reactive Protein as Potential Biomarkers for Diagnosis of Trousseau's Syndrome in Patients with Cerebral Embolism.
Tsushima Michiko,Metoki Norifumi,Hagii Joji,Saito Shin,Shiroto Hiroshi,Yasujima Minoru,Kato Tomo,Kudo Natsumi,Toyama Yuichi,Yokono Yoshikazu,Nozaka Masashi,Kawamura Yosuke,Nakata Masamichi,Tomita Hirofumi
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND:Differentiating stroke due to Trousseau's syndrome from other types of cerebral embolism is challenging, especially in patients with occult cancer. The current study aimed to determine predicting factors and biomarkers of stroke due to Trousseau's syndrome. METHODS:This retrospective study comprised 496 consecutive patients with acute cerebral embolism, including 19, 85, 310, and, 82 patients with stroke due to Trousseau's syndrome, artery-to-artery embolism, cardioembolic stroke, and embolic stroke with undetermined source, respectively. All patients were evaluated within 72 hours of onset. The clinical characteristics, laboratory findings, and patterns on diffusion-weighted magnetic resonance imaging (DWI) were compared among the groups. RESULTS:Plasma D-dimer and C-reactive protein (CRP) levels were significantly higher in the Trousseau's syndrome than in the other causes of cerebral embolism. Multivariate analyses demonstrated that female sex, multiple lesions on DWI, high D-dimer and CRP levels, and low platelet and low brain natriuretic peptide levels were independent predictors that could distinguish Trousseau's syndrome from the other causes of cerebral embolism. The cutoff values of D-dimer and CRP to identify stroke due to Trousseau's syndrome was 2.68 µg/mL fibrinogen equivalent units and .29 mg/dL, respectively. CONCLUSIONS:The elevated D-dimer and CRP levels on admission in addition to specific clinical features may be useful for diagnosis of Trousseau's syndrome in patients with cerebral embolism.
Clinical effects of antiplatelet drugs and statins on D-dimer levels.
Schol-Gelok Suzanne,van der Hulle Tom,Biedermann Joseph S,van Gelder Teun,Klok Frederikus A,van der Pol Liselotte M,Versmissen Jorie,Huisman Menno V,Kruip Marieke J H A
European journal of clinical investigation
BACKGROUND:Acute pulmonary embolism may be ruled out by combining nonhigh clinical probability and a normal D-dimer level. Both antiplatelet drugs and HMG-CoA reductase inhibitors (statins) have been associated with effects on thrombus formation, potentially influencing D-dimer levels in this setting, leading to a higher rate of false-negative tests. Therefore, we determined whether D-dimer levels in patients with suspected pulmonary embolism are affected by concomitant use of antiplatelet drugs and/or statins and evaluated whether the effect of antiplatelet drugs or statins might affect diagnostic accuracy. MATERIALS AND METHODS:We performed a posthoc analysis in the YEARS diagnostic study, comparing age- and sex-adjusted D-dimer levels among users of antiplatelet drugs, statins and nonusers. We then reclassified patients within the YEARS algorithm by developing a model in which we adjusted D-dimer cut-offs for statin use and evaluated diagnostic accuracy. RESULTS:We included 156 statins users, 147 antiplatelet drugs users and 726 nonusers of either drugs, all with suspected pulmonary embolism. Use of antiplatelet drugs did not have a significant effect, whereas statin use was associated with 15% decrease in D-dimer levels (95% CI, -28% to -0.6%). An algorithm with lower D-dimer thresholds in statin users yielded lower specificity (0.42 compared to 0.33) with no difference in false-negative tests. CONCLUSIONS:We conclude that use of statins but not of antiplatelet agents is associated with a modest decrease in D-dimer levels. Adjusting D-dimer cut-offs for statin use did, however, not result in a safer diagnostic strategy in our cohort.
D-Dimer Predicts Long-Term Cause-Specific Mortality, Cardiovascular Events, and Cancer in Patients With Stable Coronary Heart Disease: LIPID Study.
Simes John,Robledo Kristy P,White Harvey D,Espinoza David,Stewart Ralph A,Sullivan David R,Zeller Tanja,Hague Wendy,Nestel Paul J,Glasziou Paul P,Keech Anthony C,Elliott John,Blankenberg Stefan,Tonkin Andrew M,
BACKGROUND:D-dimer, a degradation product of cross-linked fibrin, is a marker for hypercoagulability and thrombotic events. Moderately elevated levels of D-dimer are associated with the risk of venous and arterial events in patients with vascular disease. We assessed the role of D-dimer levels in predicting long-term vascular outcomes, cause-specific mortality, and new cancers in the LIPID trial (Long-Term Intervention with Pravastatin in Ischaemic Disease) in the context of other risk factors. METHODS:LIPID randomized patients to placebo or pravastatin 40 mg/d 5 to 38 months after myocardial infarction or unstable angina. D-dimer levels were measured at baseline and at 1 year. Median follow-up was 6.0 years during the trial and 16 years in total. RESULTS:Baseline D-dimer levels for 7863 patients were grouped by quartile (≤112, 112-173, 173-273, >273 ng/mL). Higher levels were associated with older age, female sex, history of hypertension, poor renal function, and elevated levels of B-natriuretic peptide, high-sensitivity C-reactive protein, and sensitive troponin I (each P<0.001). During the first 6 years, after adjustment for up to 30 additional risk factors, higher D-dimer was associated with a significantly increased risk of a major coronary event (quartile 4 versus 1: hazard ratio [HR], 1.45; 95% confidence interval, 1.21-1.74), major cardiovascular disease (CVD) event (HR, 1.45; 95% confidence interval, 1.23-1.71) and venous thromboembolism (HR, 4.03; 95% confidence interval, 2.31-7.03; each P<0.001). During the 16 years overall, higher D-dimer was an independent predictor of all-cause mortality (HR, 1.59), CVD mortality (HR, 1.61), cancer mortality (HR, 1.54), and non-CVD noncancer mortality (HR, 1.57; each P<0.001), remaining significant for deaths resulting from each cause occurring beyond 10 years of follow-up (each P≤0.01). Higher D-dimer also independently predicted an increase in cancer incidence (HR, 1.16; P=0.02).The D-dimer level increased the net reclassification index for all-cause mortality by 4.0 and venous thromboembolism by 13.6. CONCLUSIONS:D-dimer levels predict long-term risk of arterial and venous events, CVD mortality, and non-CVD noncancer mortality independent of other risk factors. D-dimer is also a significant predictor of cancer incidence and mortality. These results support an association of D-dimer with fatal events across multiple diseases and demonstrate that this link extends beyond 10 years' follow-up.
A revised systematic review and meta-analysis on the effect of statins on D-dimer levels.
Schol-Gelok Suzanne,Morelli Francesca,Arends Lidia R,Boersma Eric,Kruip Marieke J H A,Versmissen Jorie,van Gelder Teun
European journal of clinical investigation
BACKGROUND:D-dimers are generated during endogenous fibrinolysis of a blood clot and have a central role in diagnostic algorithms to rule out venous thromboembolism. HMG-CoA reductase inhibitors, more commonly called statins, are known to have effects independent of LDL-cholesterol lowering, including antithrombotic properties. An effect of statins on D-dimer levels has been reported in a prior systematic review and meta-analysis, but methodological shortcomings might have led to an overestimated effect. To re-evaluate the association between statins and D-dimer levels, we systematically reviewed all published articles on the influence of statins on D-dimer levels and conducted a novel meta-analysis (PROSPERO registration number CRD42017058932). MATERIALS AND METHODS:We electronically searched EMBASE, Medline Epub, Cochrane, Web of Science and Google Scholar (100 top relevance) (date of last search: 5 October 2017). We included randomized controlled trials, cohort studies and cross-sectional studies. Two reviewers independently screened all articles retrieved and extracted data on study and patient characteristics, study quality and D-dimer levels. RESULTS:Study-level meta-analysis involving 18,052 study participants showed lower D-dimer levels in those receiving statin treatment than controls (SMD: -0.165, 95% CI -0.234; -0.096, P = <0.001). Sensitivity analyses and additional analyses on treatment duration (<12 weeks vs ≥12 weeks) and type of statin (lipophilic or hydrophilic) did not modify this overall result. CONCLUSION:This meta-analysis suggests an association between use of statins and reduction of D-dimer levels, independent of treatment duration and type of statin used. This effect is small but robust, and should be interpreted with caution.