Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability.
Kearon Clive,de Wit Kerstin,Parpia Sameer,Schulman Sam,Afilalo Marc,Hirsch Andrew,Spencer Frederick A,Sharma Sangita,D'Aragon Frédérick,Deshaies Jean-François,Le Gal Gregoire,Lazo-Langner Alejandro,Wu Cynthia,Rudd-Scott Lisa,Bates Shannon M,Julian Jim A,
The New England journal of medicine
BACKGROUND:Retrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP. METHODS:We performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism. RESULTS:A total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, -17.6 percentage points; 95% CI, -19.2 to -15.9). CONCLUSIONS:A combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGeD ClinicalTrials.gov number, NCT02483442.).
Venous Thromboembolism and Pulmonary Embolism: Strategies for Prevention and Management.
Blitzer Rachel R,Eisenstein Samuel
The Surgical clinics of North America
Perioperative venous thromboembolism (VTE) is a common complication within the surgical patient population. Perioperative mechanical and chemoprophylaxis have been shown to reduce the incidence of both deep venous thrombosis and pulmonary embolism. Prophylactic regimen must be tailored to the patient's individual risk factors as well as the nature of the procedure. In the event of VTE, treatment most commonly includes long-term anticoagulation, whereas more severe cases may require lytic or mechanical interventions.
Trends in risk stratification, in-hospital management and mortality of patients with acute pulmonary embolism: an analysis from China pUlmonary thromboembolism REgistry Study (CURES).
Zhai Zhenguo,Wang Dingyi,Lei Jieping,Yang Yuanhua,Xu Xiaomao,Ji Yingqun,Yi Qun,Chen Hong,Hu Xiaoyun,Liu Zhihong,Mao Yimin,Zhang Jie,Shi Juhong,Zhang Zhu,Wu Sinan,Gao Qian,Tao Xincao,Xie Wanmu,Wan Jun,Zhang Yunxia,Zhang Shuai,Zhen Kaiyuan,Zhang Zhonghe,Fang Baomin,Wang Chen,
The European respiratory journal
BACKGROUND:Similar trends of management and in-hospital mortality of acute pulmonary embolism (PE) have been reported in European and American populations. However, these tendencies were not clear in Asian countries. OBJECTIVES:We retrospectively analyzed the trends of risk stratification, management and in-hospital mortality for patients with acute PE through a multicenter registry in China (CURES). METHODS:Adult patients with acute symptomatic PE were included between 2009 and 2015. Trends in disease diagnosis, treatment and death in hospital were fully analyzed. Risk stratification was retrospectively classified by hemodynamical status and the simplified Pulmonary Embolism Severity Index (sPESI) score according to the 2014 European Society of Cardiology/European Respiratory Society guidelines. RESULTS:Among overall 7438 patients, the proportions with high (hemodynamically instability), intermediate (sPESI≥1) and low (sPESI=0) risk were 4.2%, 67.1% and 28.7%, respectively. was the widely employed diagnostic approach (87.6%) and anticoagulation was the frequently adopted initial therapy (83.7%). Between 2009 and 2015, a significant decline was observed for all-cause mortality (from 3.1% to 1.3%, adjusted =0.0003), with a concomitant reduction in use of initial systemic thrombolysis (from 14.8% to 5.0%, <0.0001). The common predictors for all-cause mortality shared by hemodynamically stable and unstable patients were co-existing cancer, older age, and impaired renal function. CONCLUSIONS:The considerable reduction of mortality over years was accompanied by changes of initial treatment. These findings highlight the importance of risk stratification-guided management throughout the nation.
Diagnostic Performance of Pulmonary Embolism Imaging in Patients with History of Asthma.
Lazarus Matthew S,Kim Yoel,Mathai Bertin,Levsky Jeffrey M,Freeman Leonard M,Haramati Linda B,Moadel Renee M
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Asthma and pulmonary embolism (PE) can present with overlapping symptoms, and distinguishing between these 2 conditions can be challenging. Asthma may limit imaging for PE because of either worsened ventilation defects on ventilation-perfusion scanning (VQ) or increased motion artifacts on CT pulmonary angiography (CTPA). We identified adults evaluated for PE with VQ or CTPA from 2012 to 2016. Patients with chronic lung disease (other than asthma) were excluded. Studies were classified as negative, positive, or nondiagnostic. Follow-up of negative cases was reviewed to determine the rate of repeat exams (within 1 wk) and the false-negative rate (defined as diagnosis of venous thromboembolism within 90 d). We reviewed 19,412 adults (aged 52 ± 18 y, 70% women) evaluated for PE (60% with VQ, 40% with CTPA); 23% had a history of asthma. Nondiagnostic results were comparable for those with and without asthma for both VQ (asthma, 3.3%; nonasthma, 3.8%; = 0.223) and CTPA (asthma, 1.6%; nonasthma, 1.5%; = 0.891). A history of asthma was not associated with a higher rate of repeat exams after negative imaging for VQ (asthma, 1.9%; nonasthma, 2.1%; = 0.547) or CTPA (asthma, 0.6%; nonasthma, 0.6%; = 0.796), nor was a history of asthma associated with a higher false-negative rate for VQ (asthma, 0.4%; nonasthma, 0.9%; = 0.015) or CTPA (asthma, 1.9%; nonasthma 1.5%; = 0.347). A history of asthma in the preceding 10 y was not associated with impaired diagnostic performance of PE imaging for either VQ or CTPA.
Right ventricle assessment in patients with pulmonary embolism at low risk for death based on clinical models: an individual patient data meta-analysis.
Becattini Cecilia,Maraziti Giorgio,Vinson David R,Ng Austin C C,den Exter Paul L,Côté Benoit,Vanni Simone,Doukky Rami,Khemasuwan Danai,Weekes Anthony J,Soares Thiago Horta,Ozsu Savas,Polo Friz Hernan,Erol Serhat,Agnelli Giancarlo,Jiménez David
European heart journal
AIMS:Patients with acute pulmonary embolism (PE) at low risk for short-term death are candidates for home treatment or short-hospital stay. We aimed at determining whether the assessment of right ventricle dysfunction (RVD) or elevated troponin improves identification of low-risk patients over clinical models alone. METHODS AND RESULTS:Individual patient data meta-analysis of studies assessing the relationship between RVD or elevated troponin and short-term mortality in patients with acute PE at low risk for death based on clinical models (Pulmonary Embolism Severity Index, simplified Pulmonary Embolism Severity Index or Hestia). The primary study outcome was short-term death defined as death occurring in hospital or within 30 days. Individual data of 5010 low-risk patients from 18 studies were pooled. Short-term mortality was 0.7% [95% confidence interval (CI) 0.4-1.3]. RVD at echocardiography, computed tomography or B-type natriuretic peptide (BNP)/N-terminal pro BNP (NT-proBNP) was associated with increased risk for short-term death (1.5 vs. 0.3%; OR 4.81, 95% CI 1.98-11.68), death within 3 months (1.6 vs. 0.4%; OR 4.03, 95% CI 2.01-8.08), and PE-related death (1.1 vs. 0.04%; OR 22.9, 95% CI 2.89-181). Elevated troponin was associated with short-term death (OR 2.78, 95% CI 1.06-7.26) and death within 3 months (OR 3.68, 95% CI 1.75-7.74). CONCLUSION:RVD assessed by echocardiography, computed tomography, or elevated BNP/NT-proBNP levels and increased troponin are associated with short-term death in patients with acute PE at low risk based on clinical models. RVD assessment, mainly by BNP/NT-proBNP or echocardiography, should be considered to improve identification of low-risk patients that may be candidates for outpatient management or short hospital stay.
Submassive Pulmonary Embolism.
Rali Parth M,Criner Gerard J
American journal of respiratory and critical care medicine
Pulmonary embolism (PE) presents a spectrum of hemodynamic consequences, ranging from being asymptomatic to a life-threatening medical emergency. Management of submassive and massive PE often involves clinicians from multiple specialties, which can potentially delay the development of a unified treatment plan. In addition, patients with submassive PE can deteriorate after their presentation and require escalation of care. Underlying comorbidities such as chronic obstructive pulmonary disease, cancer, congestive heart failure, and interstitial lung disease can impact the patient's hemodynamic ability to tolerate submassive PE. In this review, we address the definitions, risk stratification (clinical, laboratory, and imaging), management approaches, and long-term outcomes of submassive PE. We also discuss the role of the PE response team in management of patients with PE.
Overview of Management of Intermediate- and High-Risk Pulmonary Embolism.
Tapson Victor F,Weinberg Aaron S
Critical care clinics
Anticoagulation is the cornerstone of acute pulmonary embolism (PE) therapy. Intermediate-risk (submassive) or high-risk (massive) PE patients have higher mortality than low-risk patients. It is generally accepted that high-risk PE patients should be considered for more aggressive therapy. Intermediate-risk patients can be subdivided, although more than simply categorizing the patient is required to guide therapy. Therapeutic approaches depend on a prompt, detailed evaluation, and PE response teams may help with rapid assessment and initiation of therapy. More clinical trial data are needed to guide clinicians in the management of acute intermediate- and high-risk PE patients.
Thrombolytic therapy for pulmonary embolism.
Zuo Zhiliang,Yue Jirong,Dong Bi Rong,Wu Taixiang,Liu Guan J,Hao Qiukui
The Cochrane database of systematic reviews
BACKGROUND:Thrombolytic therapy is usually reserved for people with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clots more rapidly than heparin and may reduce the death rate associated with PE. However, there are still concerns about the possible risk of adverse effects of thrombolytic therapy, such as major or minor haemorrhage. This is the fourth update of the Cochrane review first published in 2006. OBJECTIVES:To assess the effects of thrombolytic therapy for acute pulmonary embolism. SEARCH METHODS:The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 August 2020. We undertook reference checking to identify additional studies. SELECTION CRITERIA:We included randomised controlled trials (RCTs) that compared thrombolytic therapy followed by heparin versus heparin alone, heparin plus placebo, or surgical intervention for people with acute PE (massive/submassive). We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug. DATA COLLECTION AND ANALYSIS:Two review authors (ZZ, QH) assessed the eligibility and risk of bias of trials and extracted data. We calculated effect estimates using the odds ratio (OR) with a 95% confidence interval (CI) or the mean difference (MD) with a 95% CI. The primary outcomes of interest were death, recurrence of PE and haemorrhagic events. We assessed the certainty of the evidence using GRADE criteria. MAIN RESULTS:We identified three new studies for inclusion in this update. We included 21 trials in the review, with a total of 2401 participants. No studies compared thrombolytics versus surgical intervention. We were not able to include one study in the meta-analysis because it provided no extractable data. Most studies carried a high or unclear risk of bias related to randomisation and blinding. Meta-analysis showed that, compared to control (heparin alone or heparin plus placebo), thrombolytics plus heparin probably reduce both the odds of death (OR 0.58, 95% CI 0.38 to 0.88; 19 studies, 2319 participants; low-certainty evidence), and recurrence of PE (OR 0.54, 95% CI 0.32 to 0.91; 12 studies, 2050 participants; low-certainty evidence). Effects on mortality weakened when six studies at high risk of bias were excluded from analysis (OR 0.71, 95% CI 0.45 to 1.13; 13 studies, 2046 participants) and in the analysis of submassive PE participants (OR 0.61, 95% CI 0.37 to 1.02; 1993 participants). Effects on recurrence of PE also weakened after removing one study at high risk of bias for sensitivity analysis (OR 0.60, 95% CI 0.35 to 1.04; 11 studies, 1949 participants). We downgraded the certainty of evidence to low because of 'Risk of bias' concerns. Major haemorrhagic events were probably more common in the thrombolytics group than in the control group (OR 2.84, 95% CI 1.92 to 4.20; 15 studies, 2101 participants; moderate-certainty evidence), as were minor haemorrhagic events (OR 2.97, 95% CI 1.66 to 5.30; 13 studies,1757 participants; low-certainty evidence). We downgraded the certainty of the evidence to moderate or low because of 'Risk of bias' concerns and inconsistency. Haemorrhagic stroke may occur more often in the thrombolytics group than in the control group (OR 7.59, 95% CI 1.38 to 41.72; 2 studies, 1091 participants). Limited data indicated that thrombolytics may benefit haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment, echocardiograms, pulmonary hypertension, coagulation parameters, composite clinical outcomes, need for escalation and survival time to a greater extent than heparin alone. However, the heterogeneity of the studies and the small number of participants involved warrant caution when interpreting results. The length of hospital stay was shorter in the thrombolytics group than in the control group (mean difference (MD) -1.40 days, 95% CI -2.69 to -0.11; 5 studies, 368 participants). Haemodynamic decompensation may occur less in the thrombolytics group than in the control group (OR 0.36, 95% CI 0.20 to 0.66; 3 studies, 1157 participants). Quality of life was similar between the two treatment groups. None of the included studies provided data on post-thrombotic syndrome or on cost comparison. AUTHORS' CONCLUSIONS:Low-certainty evidence suggests that thrombolytics may reduce death following acute pulmonary embolism compared with heparin (the effectiveness was mainly driven by one trial with massive PE). Thrombolytic therapy may be helpful in reducing the recurrence of pulmonary emboli but may cause more major and minor haemorrhagic events, including haemorrhagic stroke. More studies of high methodological quality are needed to assess safety and cost effectiveness of thrombolytic therapy for people with pulmonary embolism.