Pharmacological prophylaxis of venous thromboembolism during acute phase of spontaneous intracerebral hemorrhage: what do we know about risks and benefits?
Masotti Luca,Godoy Daniel Agustin,Di Napoli Mario,Rabinstein Alejandro A,Paciaroni Maurizio,Ageno Walter
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
Spontaneous intracerebral hemorrhage (sICH) represents a devastating clinical event with high mortality and morbidity rates. Only few patients with sICH are treated with neurosurgical evacuation of the hematoma, and the majority of them need only a good conservative medical approach. The goal of medical treatment is to avoid secondary neurological and systemic complications. Venous thromboembolism (VTE) represents one of the most feared complications of sICH, and it is a potential cause of death. The balance between the benefit of VTE prevention and the risk of hematoma enlargement and/or rebleeding with the use of pharmacologic thromboprophylaxis remains controversial because of the lack of consistent evidences in the literature. The efficacy of mechanical prophylaxis is also uncertain. Consequently, until now there are no clear guidelines and scientific evidences available for physicians in this field. The aim of this review is to analyze the available literature and guidelines about pharmacological VTE prophylaxis in patients with nonsurgical sICH.
Venous thromboembolism prevention during the acute phase of intracerebral hemorrhage.
Zeng Zhou,Hu Zhiping,Zhang Jie
Journal of the neurological sciences
BACKGROUND:Although knowledge of intracerebral hemorrhage (ICH) continues to evolve, it is still a major cause of morbidity and mortality worldwide. Venous thromboembolism (VTE) events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), are common and preventable complications of ICH. On the basis of the current systematic review and guidelines, the optimal prophylactic treatment remains unclear. SUMMARY:In this review, we used the existing literature to provide an overview of the prevalence, treatment, guidelines, and worldwide trend and future issues regarding VTE events after ICH. KEY MESSAGES:Briefly, VTE events are common, with severe complications following ICH. Clinicians should be familiar with the current guidelines and trials to identify the optimal treatment for every patient's unique condition.
Safety of Chemical DVT Prophylaxis in Severe Traumatic Brain Injury with Invasive Monitoring Devices.
Dengler Bradley A,Mendez-Gomez Paolo,Chavez Amanda,Avila Lacey,Michalek Joel,Hernandez Brian,Grandhi Ramesh,Seifi Ali
BACKGROUND:Patients with traumatic brain injuries (TBIs) have an increased risk of developing a deep vein thrombosis (DVT), but the risk of hemorrhage expansion with intracranial monitoring devices remains unknown. We sought to determine the safety of chemical DVT prophylaxis in severe TBI patients with invasive intracranial pressure monitors. METHODS:We retrospectively reviewed all patients with severe TBI admitted to the neurosurgical intensive care unit of a large tertiary care center over a three-year period. RESULTS:155 patients were included with an incidence of DVT of 12 %. The median length of time to a stable head CT was 2 days, and the median time to initiation of chemical DVT prophylaxis was 3.6 days. The odds of DVT increased with intraparenchymal hemorrhage [OR 7.21, 95 % CI (1.43-36.47), p = 0.0169], non-White ethnicity [OR 7.86, 95 % CI (1.23-50.35), p = 0.0295], female gender [OR 13.93, 95 % CI (2.47-78.73), p = 0.0029], smoking [OR 4.32, 95 % CI (1.07-17.51), p = 0.0405], no anticoagulation [OR 25.39, 95 % CI (4.26-151.48), p < 0.001], and an IVC filter [OR 15.82, 95 % CI (3.14-79.76), p < 0.001]. Twenty-eight (18 %) of these subjects experienced in-hospital mortality. The risk of in-hospital death was significantly increased among those who did not receive anticoagulation. This study found no association between DVT formation, hemorrhage expansion, or increased risk from invasive monitoring devices between various doses of unfractionated heparin (UH) and low-molecular-weight heparin (LMWH). CONCLUSION:We conclude that DVT prophylaxis with either LMWH or UH is safe with intracranial pressure monitors in place.
Mortality in cerebral venous thrombosis: results from the national inpatient sample database.
Nasr D M,Brinjikji W,Cloft H J,Saposnik G,Rabinstein A A
Cerebrovascular diseases (Basel, Switzerland)
BACKGROUND:Outcomes of cerebral venous thrombosis (CVT) vary from full recovery to death. Few studies have been performed examining epidemiologic and medical risk factors associated with high mortality in CVT. In this study, we examined the National Inpatient Sample (NIS) to determine the epidemiologic and medical risk factors associated with increased mortality from CVT. MATERIALS AND METHODS:Using the NIS from 2001 to 2008, patients who suffered from CVT were identified using the ICD-9 codes 437.6 (nonpyogenic thrombosis of intracranial venous sinus), 325 (phlebitis and thrombophlebitis of intracranial venous sinuses) and 671.5 (peripartum phlebitis and thrombosis, cerebral venous thrombosis, thrombosis of intracranial venous sinus). We analyzed the associations of demographic factors, risk factors, comorbidities, complications of CVT, and therapeutic interventions with in-hospital mortality. We performed a multivariate logistic regression analysis to determine which variables were independently associated with in-hospital mortality. RESULTS:11,400 patients were hospitalized with CVT between 2001 and 2008. Two-hundred and thirty-two (2.0%) suffered in-hospital mortality. Patients 15-49 years old had the lowest mortality rate (1.5%) compared with 2.8% for patients aged 50-64 (p < 0.001) and 6.1% for patients ≥65 years old (p < 0.001). The most common condition associated with CVT was pregnancy/puerperium (24.6%), and these women had a low mortality rate (0.4%). On multivariate analysis, the comorbidity most strongly associated with increased risk of mortality was sepsis (mortality rate 15.6%, OR = 7.5, 95% CI = 4.79-11.53, p < 0.001). Malignancy, underlying autoimmune disease and substance abuse were also independently associated with mortality, but with lower mortality rates (<5%). Complications associated with increased risk of mortality included paralysis (8.0%, OR = 3.4, 95% CI = 3.17-6.96, p < 0.001), intracranial hemorrhage (8.7%, OR = 5.4, 95% CI = 4.38-7.96, p < 0.001), and hydrocephalus (15.0%, OR = 3.2, 95% CI = 5.54-15.11, p = 0.004). Demographic variables associated with decreased mortality on multivariate analysis were male gender (2.1%, OR = 0.62, 95% CI = 0.43-0.87, p = 0.006) and Asian/Pacific Islander race (OR = 0.00, 95% CI = 0-0.27, p < 001). CONCLUSIONS:CVT is associated with a low in-hospital mortality rate. Amongst patients suffering CVT, male gender and Asian/Pacific Islander race were independently associated with lower odds of in-hospital mortality when compared to their female and white counterparts, respectively. Septic patients with CVT have the greatest risk of in-hospital mortality. Hydrocephalus, intracranial hemorrhage, and motor deficits are also associated with higher risk of death. Our results build on previous evidence that serves to define a group of patients with CVT at high risk of early death.
Major bleeding after hospitalization for deep-venous thrombosis.
White R H,Beyth R J,Zhou H,Romano P S
The American journal of medicine
PURPOSE:Most studies of oral anticoagulant-related bleeding have analyzed the incidence of adverse outcomes among patients with a variety of different conditions and without any comparison with a control group. We determined the incidence, time course, and risk factors associated with major bleeding after hospital discharge among patients with deep-vein thrombosis, and estimated the excess risk of bleeding associated with oral anticoagulant therapy. METHODS:A total of 22,000 adults were hospitalized in California for 3 or more days with a diagnosis of deep-venous thrombosis between January 1, 1992, and September 30, 1994. We determined the risk factors associated with readmission for bleeding. We compared the incidence of readmission for bleeding with comparison cohorts of patients with pneumonia or cellulitis who were matched for age, gender, race, and length of hospital stay. RESULTS:Of 21,250 patients with deep-venous thrombosis who were discharged without bleeding, 1.4% were readmitted for bleeding within 91 days; the rate was 2.7 times greater in the first 30 days than in the next 61 days. Risk factors for bleeding included hospitalization with gastrointestinal bleeding during the previous 18 months (relative hazard [RH] = 2.6, 95% confidence interval [CI]: 1.6 to 4.1), hospitalization with an alcohol-related diagnosis during the previous 18 months (RH = 2.6, 95% CI: 1.4 to 4.8), chronic renal disease (RH = 2.4, 95% CI: 1.4 to 4.2), female gender (RH = 1.7, 95% CI: 1.3 to 2.2), presence of a malignancy (RH = 1.6, 95% CI: 1.2 to 2.2), nonwhite race (RH = 1.6, 95% CI: 1.2 to 2.1), and age over 65 years (RH = 1.3, 95% CI: 1.0 to 1.7). Significantly more women (n = 40) had intracranial bleeding than men (n = 18, P = 0.02). In the comparison cohorts, the incidence of readmission for bleeding within 3 months of discharge was 0.7%, and the relative risk (RR) of readmission was greater in those with deep-venous thrombosis than in those with cellulitis (RR = 2.0, 95% CI: 1.6 to 2.5) or pneumonia (RR = 2.0, 95% CI: 1.7 to 2.5). CONCLUSIONS:The incidence of rehospitalization for bleeding was greatest in the first 30 days after discharge, and was approximately twice that seen in patients hospitalized for cellulitis or pneumonia. Further studies are needed to determine why women and nonwhite patients are at increased risk for anticoagulant-related bleeding.
Higher risk of deep vein thrombosis after hemorrhagic stroke than after acute ischemic stroke.
Ji Ruijun,Li Guoyang,Zhang Runhua,Hou Huiqing,Zhao Xingquan,Wang Yongjun
Journal of vascular nursing : official publication of the Society for Peripheral Vascular Nursing
Patients with stroke are at particularly increased risk of developing deep vein thrombosis (DVT) during hospitalization. In this study, we aimed to compare the potential risk of in-hospital DVT by stroke subtypes. This study is based on a prospective cohort (in-hospital medical complication after acute stroke [iMCAS] registry) enrolling patients with acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). In-hospital DVT was diagnosed by clinical manifestations and verified by compression Doppler ultrasound. A logistic regression analysis was performed to assess the association between stroke subtypes and occurrence of DVT. A total number of 1,771 patients were enrolled in the iMCAS. The mean age was 57.1 ± 12.9 years, and 27.5% were female patients. The median length of stay was 14 days (interquartile range [IQR], 11-16). The median National Institutes of Health Stroke Scale score on admission for patients with AIS, ICH, and SAH was 4 (IQR: 2-8), 4 (IQR:1-10), and 0 (IQR:0-0), respectively. In-hospital DVT after AIS, ICH, and SAH was 1.9%, 5.7%, and 7.9%, respectively. The median time from stroke onset to DVT formation after AIS, ICH, and SAH was 10.5 days (IQR: 3.8-14.5), 7.5 days (IQR:4.0-9.5), and 7.0 days (IQR:5.0-12.5), respectively. After adjusting for potential confounders, patients with ICH (odds ratio = 7.350; 95% confidence interval = 2.411-22.13; P < .001) and SAH (odds ratio = 11.92; 95% confidence interval = 5.192-27.38; P < .001) had significantly higher risk of in-hospital DVT than those patients with AIS. In conclusion, patients with hemorrhagic stroke (ICH and SAH) have significantly higher risk of in-hospital DVT than patients with AIS. Further studies on pathophysiologic mechanisms are warranted.
Comparing pharmacological venous thromboembolism prophylaxis to intermittent pneumatic compression in acute intracerebral haemorrhage: protocol for a systematic review and network meta-analysis.
Yogendrakumar Vignan,Lun Ronda,Hutton Brian,Fergusson Dean A,Dowlatshahi Dar
INTRODUCTION:Patients with an intracerebral haemorrhage are at increased risk of venous thromboembolism. Pharmacotherapy and pneumatic compression devices are capable of preventing venous thromboembolism, however both interventions have limitations. There are no head-to-head comparisons between these two interventions. To address this knowledge gap, we plan to perform a systematic review and network meta-analysis to examine the comparative effectiveness of pharmacological prophylaxis and mechanical compression devices in the context of intracerebral haemorrhage. METHODS AND ANALYSIS:MEDLINE, PUBMED, EMBASE, CENTRAL, ClinicalTrials.gov and the Internet Stroke Trials Registry will be searched with assistance from an experienced information specialist. Eligible studies will include those that have enrolled adults presenting with spontaneous intracerebral haemorrhage and compared one or more of the respective interventions against each other and/or a control. Primary outcomes to be assessed are occurrence of new venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) and haematoma expansion, defined as a significant enlargement of baseline haemorrhage or new haemorrhage occurrence. Both randomised and non-randomised comparative studies will be included. Data on participant characteristics, study design, intervention details and outcomes will be extracted. Study quality will be assessed using the Cochrane Risk of Bias Tool and the Robins-I tool. Bayesian network meta-analyses will be performed to compare interventions based on all available direct and indirect evidence. If the transitivity assumption for network meta-analysis cannot be met, we will perform a qualitative assessment. ETHICS AND DISSEMINATION:Formal ethics is not required as primary data will not be collected. The findings of this study will be disseminated through conference presentations, and peer-reviewed publications. In an area of clinical practice where equipoise exists, the findings of this study may assist in determining which treatment intervention is most effective in venous thromboembolism prevention. PROSPERO REGISTRATION NUMBER:CRD42018090960.
Serum neuron specific enolase may be a marker to predict the severity and outcome of cerebral venous thrombosis.
Hu Yanyu,Meng Ran,Zhang Xuxiang,Guo Linlin,Li Sijie,Wu Yan,Duan Jiangang,Ding Yuchuan,Ji Xunming
Journal of neurology
The objective is to explore the effective of baseline serum neuron specific enolase (NSE) on predicting the severity and outcome in patients with cerebral venous thrombosis (CVT). A total of 156 patients confirmed as CVT in Xuanwu Hospital were enrolled in this retrospective study from March 2011 through September 2016. The severity was evaluated with the National Institutes of Health Stroke Score (NIHSS), intracranial pressure (ICP), and CVT-related complications; the outcome was evaluated by modified Rankin Scale (mRS); the relationship between baseline serum NSE and mRS was analyzed with receiver operating characteristic curve (ROC), logistic regression analysis, and Kaplan-Meier curves. Baseline level of serum NSE was positively associated with baseline NIHSS (r = 0.322, p < 0.001). Among which, patients with high level of serum NSE were also noticed with cerebral venous infarction (p < 0.001), intracranial hemorrhage (p < 0.001), seizure (p = 0.035). Meanwhile, patients in NSE ≥ 15.05 ng/mL group vs. NSE < 15.05 ng/mL group had large mRS scores (≥ 3) at discharge (adjusted OR: 5.40, 95% CI 1.27-22.91; p = 0.022) and higher percentage of mRS scores ≥ 3 during 40 months of outpatient follow-up (log-rank p < 0.001). Baseline level of serum NSE is positively associated with the severity of CVT. Presumably NSE may be a potential predictor for the clinical outcome of CVT.
Management of a decompensated acute-on-chronic intracranial venous sinus thrombosis.
Serna Candel Carmen,Hellstern Victoria,Beitlich Tania,Aguilar Pérez Marta,Bäzner Hansjörg,Henkes Hans
Therapeutic advances in neurological disorders
A 34-year-old female patient presented during the 10th week of her second gravidity with headache, nausea and vomiting 2 weeks before admission. Her medical history was remarkable for a heterozygous factor V Leiden mutation, elevated lipoprotein A, and a cerebral venous thrombosis (CVT) after oral contraceptive intake 15 years before. Magnetic resonance imaging (MRI) suggested acute and massive intracranial sinus thrombosis. Despite full-dose anticoagulation, the patient deteriorated clinically and eventually became comatose. Now, MRI/magnetic resonance angiography revealed vasogenic edema of both thalami, of the left frontal lobe, and of the head of the caudate nucleus, with venous stasis and frontal petechial hemorrhage. She was referred for endovascular treatment. Diagnostic angiography confirmed a complete superficial and deep venous sinus occlusion. Endovascular access to the straight and superior sagittal sinus was possible, but neither rheolysis nor balloon angioplasty resulted in recanalization of the venous sinuses. Monitored heparinization was continued and antiaggregation was initiated. The patient remained comatose for another 5 days and MRI showed progress of the cytotoxic edema. On day 6, infusion of eptifibatide at body-weight-adapted dosage was started. The following day, the patient improved and slowly regained consciousness. MRI confirmed regression of the edema. The eptifibatide infusion was continued for a total of 14 days. Thereafter two doses of 180 mg ticagrelor (PO) daily were started. The patient remained on acetylsalicylic acid (ASA), ticagrelor, and enoxaparin on an unchanged dosage regimen. She was discharged home 26 days after the endovascular treatment without serious neurological deficit, with the pregnancy intact. At the 30th week of pregnancy the dosage of ASA was reduced to 300 mg once PO daily. Cesarian delivery was carried out at the 38th week of pregnancy. The newborn was completely healthy. Ultima ratio therapeutic options for severe intracranial venous sinus thrombosis refractory to anticoagulation are discussed, with an emphasis on platelet-function inhibition.
Prevention of deep venous thrombosis and pulmonary embolism following stroke: a systematic review of published articles.
André C,de Freitas G R,Fukujima M M
European journal of neurology
We performed a systematic review of the literature on venous thromboembolism (VTE) prophylaxis following cerebral infarct (CI) and haemorrhagic stroke. MEDLINE, Cochrane, LILACS and SciELO databases were scanned, and the Abstracts from Brazilian, American and European Neurology and Stroke Congresses were scrutinized for clinical trials. Moreover, the reference lists of articles and reviews were searched. A pooled analysis of two large studies with aspirin was made. Both unfractionated heparin and low molecular weight heparins/heparinoids (LMWH) are partially effective for VTE prophylaxis after CI, and should be routinely used in patients with motor deficit and reduced mobility and no contraindications. Reduction of deep venous thrombosis is better established than the effect over pulmonary embolism or mortality. Some evidence points to a greater efficacy of LMWH. The available evidence does not support the use of mechanical methods or dextran. Aspirin may have a mild protective effect. Low-dose Warfarin might be useful in the rehabilitation setting. Strict recommendations cannot be made in patients with haemorrhagic stroke but intermittent pneumatic compression merits further study. There are important limitations of current VTE preventive strategies following stroke. Additional studies on the combination of methods after CI and of low doses of anticoagulants following cerebral haemorrhage are urgently needed.
A Retrospective Study on Risk Factors for Urinary Tract Infection in Patients with Intracranial Cerebral Hemorrhage.
Mu Jingsong,Ni Chaomin,Wu Ming,Fan Wenxiang,Liu Zheng,Xu Fengjuan,Liu Lei
BioMed research international
Objective:This study aimed to explore the risk factors of urinary tract infection (UTI) in patients with intracranial cerebral hemorrhage (ICH). Design:This is a retrospective study, and a total of 77 patients with ICH consecutively admitted to the First Affiliated Hospital of USTC (Anhui Provincial Hospital, Hefei, China) during the period of August 2015 to August 2017 were included. The patients were divided into an UTI group (24 cases) and a non-UTI group (53 cases); patients with UTI were diagnosed according to clinical manifestations, recent urinary routines, and urine culture results. The following information in these two groups was recorded: age, sex, course of disease, side of paralysis, location and type of cerebral hemorrhage, disturbance of consciousness or not, the Brunnstrom stage of paralysed lower limbs, number of basic diseases, whether there were complications (tracheotomy, retention catheterization, pulmonary infection, pressure sore, deep venous thrombosis, etc.), whether rehabilitation interventions were conducted, blood routine, biochemistry index, DIC complete set, urine routine, and urine culture data. Univariate analysis and multivariate logistic regression analysis were used to examine the risk factors of UTI in patients with ICH. Results:Univariate analysis showed that age, side of paralysis, disturbance of consciousness, the Brunnstrom stage of lower limbs, tracheotomies, retention catheterization, pulmonary infection, leukocyte count, neutrophil proportion, sodium, uric acid, D-dimer, and fibrinogen may be related to UTI in patients with ICH ( < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424), < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424), < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424), < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424). Conclusions:Increased age and high D-dimer are independent risk factors for UTI in patients with ICH, while right-sided paralysis is a protective factor for UTI in patients with ICH.
Cerebral Venous Thrombosis Associated with Intracranial Hemorrhage and Timing of Anticoagulation after Hemicraniectomy.
Pizzi Michael A,Alejos David A,Siegel Jason L,Kim Betty Y S,Miller David A,Freeman William D
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND:Cerebral venous thrombosis (CVT) is a rare cerebrovascular event that can present with headache, seizure, and focal neurological deficits. Approximately 30%-40% of patients with CVT also present with intracranial hemorrhage. Current guidelines recommend anticoagulation after CVT even in the setting of intracranial hemorrhage, but the timing of initiation is unclear. We present a case of CVT where timing of anticoagulation was unclear by current guidelines. METHODS:We conducted a literature search with search terms of "cerebral venous thrombosis," "intracranial hemorrhage," and "anticoagulation." Abstracted information included anticoagulation status and time of initiation of anticoagulation. We present a 30-year-old woman with sudden onset of right hemiplegia, global aphasia, and new-onset seizures diagnosed with left transverse and sigmoid sinus thrombosis with intraparenchymal hemorrhage. The patient was treated with endovascular thrombectomy and decompressive hemicraniectomy due to hemorrhage expansion, and anticoagulation was restarted 8 days after hemicraniectomy. RESULTS:The literature review demonstrated a wide variation of timing for anticoagulation initiation in patients with CVT and intracranial hemorrhage. Most started anticoagulation within 24 hours of admission with similar functional neurological recovery. Current guidelines on the treatment of CVT, even with intracranial hemorrhage, recommend anticoagulation. Most reports in the literature state initiation of anticoagulation within 24 hours. However, the literature does not definitively state when to initiate anticoagulation in a patient with CVT, intracranial hemorrhage, thrombectomy, and decompressive hemicraniectomy. CONCLUSION:This case illustrates the challenge of determining when to resume anticoagulation for CVT.
Efficacy and safety of anticoagulants in the prevention of venous thromboembolism in patients with acute cerebral hemorrhage: a meta-analysis of controlled studies.
Paciaroni M,Agnelli G,Venti M,Alberti A,Acciarresi M,Caso V
Journal of thrombosis and haemostasis : JTH
AIM:The role of anticoagulants for the prevention of venous thromboembolism in acute hemorrhagic stroke is uncertain. We performed an updated meta-analysis of studies to obtain the best estimates of the efficacy and safety of anticoagulants for the prevention of venous thromboembolism in patients with acute hemorrhagic stroke. METHODS:Using electronic and manual searches of the literature, we identified randomized and non-randomized studies comparing anticoagulants (unfractionated heparin or low-molecular-weight heparin or heparinoids) with treatments other than anticoagulants (elastic stockings, intermittent pneumatic compression or placebo) in patients with acute hemorrhagic stroke. Study outcomes included symptomatic and asymptomatic deep venous thrombosis (DVT), symptomatic and asymptomatic pulmonary embolism (PE), any hematoma enlargement or death. Risk ratios (RRs) for individual outcomes were calculated for each study and data from all studies were pooled using the Mantel-Haenszel method. RESULTS:Four studies (two randomized) involving 1000 patients with acute hemorrhagic stroke met the criteria for inclusion in this meta-analysis. Compared with other treatments, anticoagulants were associated with a significant reduction in PE (1.7% vs. 2.9%; RR, 0.37; 95% CI, 0.17-0.80; P = 0.01), a DVT rate of 4.2% compared with 3.3% (RR, 0.77; 95% CI, 0.44-1.34; P = 0.36), an increase in any hematoma enlargement (8.0% vs. 4.0%; RR, 1.42; 95% CI, 0.57-3.53; P = 0.45), and a non-significant reduction in mortality (16.1% vs. 20.9%; RR, 0.76; 95% CI, 0.57-1.03; P = 0.07). CONCLUSIONS:Our findings indicate that in patients with hemorrhagic stroke, early anticoagulation is associated with a significant reduction in PE and a non-significant reduction in mortality, with the trade-off of a non-significant increase in hematoma enlargement. These results must be taken with caution and should encourage the assessment of the clinical benefit of antithrombotic prophylaxis in patients with cerebral bleeding by properly designed clinical trials.
Safety of Prophylactic Heparin in the Prevention of Venous Thromboembolism After Spontaneous Intracerebral Hemorrhage: A Meta-analysis.
Pan Xi,Li Jihui,Xu Lan,Deng Shengming,Wang Zhi
Journal of neurological surgery. Part A, Central European neurosurgery
OBJECTIVES: Patients with spontaneous intracerebral hemorrhage (sICH) have a nearly fourfold greater risk for venous thromboembolism (VTE) than those with acute ischemic stroke, and VTE after sICH is associated with high risk for in-hospital mortality. The benefit from prophylactic heparin for VTE remains uncertain because its safety is not documented. In this study, we used an updated meta-analysis to evaluate the safety of heparin for the prevention of VTE in patients with sICH. METHODS: Electronic databases Medline and Embase from January 1990 to November 2017 and the Cochrane Library were searched using these keywords: and We evaluated the quality of included studies according to the bias risk in the Cochrane Handbook for Systematic Reviews of Interventions v.5.1.0. All statistical analyses were performed with RevMan v.5 software (Cochrane Collaboration, London, United Kingdom). Tests of heterogeneity were conducted with the Mantel-Haenszel method. RESULTS: Nine studies involving 4,055 patients with sICH met the inclusion criteria in this meta-analysis. Of these studies, only one met all specific criteria and had a low probability of bias, whereas eight studies met only some of the criteria and had a moderate probability of bias. In comparison with non-heparin treatments, low-molecular-weight heparin or unfractionated heparin was associated with a nonsignificant increase in any hematoma enlargement, a nonsignificant reduction in extracranial hemorrhage, a nonsignificant increase in mortality, a nonsignificant increase in the number of modified Rankin Scale scores of 3 to 5, and a nonsignificant increase in numbers of Glasgow Outcome Scale scores of 2 to 3. CONCLUSION: Prophylactic heparin was associated with a nonsignificant increase in any hematoma enlargement and mortality, a nonsignificant reduction in extracranial hemorrhage, and a nonsignificant increase in the incidence of major disability in patients with sICH. It is probably safe to administer heparin to prevent VTE in patients with sICH.
Endovascular Treatment of Thrombosis and Embolism.
Goktay Ahmet Yigit,Senturk Cagin
Advances in experimental medicine and biology
Deep venous thrombosis (DVT) is a common disorder with a significant mortality rate. Successful endovascular treatment of acute DVT is most likely to be achieved in patients with recently formed thrombus, (<10-14 days) with acute iliofemoral DVT. Endovascular treatment options include: Catheter-directed thrombolysis (CDT), pharmacomechanical catheter-directed thrombolysis (PCDT), percutaneous aspiration thrombectomy (PAT), vena cava filter protection, venous balloon dilatation and venous stent implantation. Current practice shows strong clinical tendency for the use of PCDT with or without other endovascular methods and an individualized approach for each DVT patient. PMT has not received general acceptance because of the associated risk of PE and damage to venous valves caused by thrombectomy devices. PAT is most commonly used as an adjunctive endovascular technique like balloon maceration to fragment thrombus, balloon angioplasty, stent implantation and vena cava filter placement. Interventional endovascular therapies for DVT have the potential to provide PE protection and prevention of PTS. Patient centered individualized approach for endovascular DVT treatment is recommended to optimize the ideal clinical result.Acute stroke is the leading cause of death for people above the age of 60 and the fifth leading cause in people aged 15-59. Mortality during the first 30 days of ischemic stroke is 20 % and 30 % of survivors will remain permanently disabled. Acute stroke patients within the therapeutic window must receive IVrtPA unless there is a contraindication. In case of contraindication to IVrtPA or for patients out of the therapeutic window for thrombolytics, standart of care is the intraarterial treatment. Patients have to be transferred to a comprehensive stroke center with capacity of dedicated neurovascular imaging and interventional neuroradiology. Noncontrast head CT that is used to rule out hemorrhage is followed by imaging studies dedicated to show if there is reasonable penumbra to save. Intraarterial thrombolysis has the main advantage of extended therapy window, earlier and more efficient recanalization and less risk of hemorrhage due to lower doses of thrombolytics. Mechanical thrombectomy has several advantages over IV/IA fibrinolysis including faster recanalization and less risk of hemorrhage especially in large artery occlusions. ASA guidelines recommend choosing stent retrievers over other devices for mechanical thrombectomy. Better recanalization rates and less infarct volume after mechanical thrombectomy result in higher numbers of functionally independent patients compared with other treatments. Two landmark studies that were published recently, SWIFT PRIME and MR CLEAN, showed that IA treatment especially with the new stent retrievers lead to a significant increase in functional recovery and independence in daily life after an acute stroke.Cerebral venous and sinus thrombosis (CVST) comprises nearly 0.5-1 % of all stroke cases. CVST causes different neurological deficits depending on the sinus/cortical vein involved. CVST may cause death and dependency in 13.4 % of patients. CT/CT venography and MR/MR venography can be effectively used to diagnose and to follow up CVT cases. Anticoagulation with heparin is the most widely accepted therapy to prevent the expansion of the thrombus. Patients deteriorating despite heparinization and patients presenting with very severe neurological deficits must receive endovascular treatment. Endovascular methods include intrasinus infusion of thrombolytics or heparin, balloon angioplasty, mechanical thrombectomy or a combination of different techniques. There is a higher rate or recanalization with endovascular methods compared to other medical therapies.
Early thrombosis prophylaxis with enoxaparin is not associated with hematoma expansion in patients with spontaneous intracerebral hemorrhage.
Ianosi B,Gaasch M,Rass V,Huber L,Hackl W,Kofler M,Schiefecker A J,Addis A,Beer R,Rhomberg P,Pfausler B,Thomé C,Ammenwerth E,Helbok R
European journal of neurology
BACKGROUND AND PURPOSE:Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48 h. We aimed to analyze the effect of early (within 48 h) versus late (>48 h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS:We analyzed 134 consecutive patients admitted to a tertiary neurointensive care unit with diagnosed spontaneous ICH, without previous anticoagulation, severe coagulopathy, hematoma evacuation, early withdrawal of therapy or ineligibility for DVT prophylaxis according to our institutional protocol. Significant late HE was defined as ≥6 mL increase of hematoma volume between neuroimaging within 48 h and day 3-6. Multivariate analysis was performed to identify risk factors for late HE, poor 3-month outcome (modified Rankin Scale score ≥ 4) and mortality. RESULTS:Patients had a median Glasgow Coma Scale score of 14 [interquartile range (IQR), 10-15], ICH volume of 11 (IQR, 5-24) mL and were 71 (IQR, 61-76) years old. A total of 56% (n = 76) received early DVT prophylaxis, 37% (n = 50) received late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume [9.5 (IQR, 4-18.5) vs. 17.5 (IQR, 8-29) mL, P = 0.038] and were more often comatose (26% vs. 10%, P = 0.025). Significant late HE [n = 5/134 (3.7%)] was associated with larger initial ICH volume (P = 0.02) and lower thrombocyte count (P = 0.03) but not with early DVT prophylaxis (P = 0.36). Early DVT prophylaxis was not associated with worse outcome. CONCLUSION:Significant late HE is uncommon and DVT prophylaxis within 48 h of symptom onset may be safe in selected patients with ICH.
High Plasma Levels of D-Dimer Are Independently Associated with a Heightened Risk of Deep Vein Thrombosis in Patients with Intracerebral Hemorrhage.
Cheng Xuan,Zhang Lu,Xie Nan-Chang,Ma Yun-Qing,Lian Ya-Jun
Deep venous thrombosis (DVT) is a complication of stroke. Our aim was to determine whether D-dimer plasma levels at admission could be a risk factor for DVT in Chinese patients with acute intracerebral hemorrhage (ICH). From December 2012 to November 2014, all patients with first-ever acute ICH were included. At baseline, the demographical and clinical data were taken. These patients were assessed for DVT using color Doppler ultrasonography (CDUS) on 15 days after ICH and whenever clinically requested. Multivariate analyses were performed using logistic regression models. Receiver operating characteristic (ROC) curves were used to test the overall predictive accuracy of D-dimer and other markers. In our study, acute ICH was diagnosed in 265 patients and 210 completed a 15-day follow-up and were included in the analysis. Fifty-four (25.7 %) out of the 210 patients were diagnosed as DVT. Plasma D-dimer levels were significantly higher in ICH patients with DVT as compared to those without DVT (P < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that plasma D-dimer levels ≥1.20 mg/L were an independent predictor of DVT [odds ratio (OR) = 12.99, 95 % confidence interval (CI) = 3.17-32.98; P < 0.0001]. With an area under the curve (AUC) of 0.91 (95 % CI = 0.86-0.94), D-dimer showed a significantly greater discriminatory ability to predict DVT as compared with high-sensitivity C-reactive protein (Hs-CRP) (AUC = 0.77, 95 % CI = 0.70-0.82; P < 0.01), homocysteine (HCY) (AUC = 0.75, 95 % CI = 0.70-0.81; P < 0.01), and National Institutes of Health Stroke Scale (NIHSS) score (AUC = 0.80, 95 % CI = 0.72-0.85; P < 0.01). The present study suggested that elevated D-dimer plasma levels were independent predictors for DVT in Chinese patients with ICH.
Predictors of deep-vein thrombosis in subarachnoid hemorrhage: a retrospective analysis.
Geraldini Federico,De Cassai Alessandro,Correale Christelle,Andreatta Giulio,Grandis Marzia,Navalesi Paolo,Munari Marina
BACKGROUND:Subarachnoid hemorrhage is a severe subtype of hemorrhagic stroke, and deep-vein thrombosis is a frequent complication detected in these patients. In addition to other well-established risk factors, the early activation of coagulation systems present in patients with subarachnoid hemorrhage could potentially play a role in the incidence of deep-vein thrombosis. This study aims to identify possible predictors for deep-vein thrombosis related to subarachnoid hemorrhage. METHODS:We conducted a retrospective cohort study on patients with a diagnosis of subarachnoid hemorrhage who presented to our institution between 1 January 2014 and 1 August 2018. We reviewed electronic medical records and analyzed several parameters such as Fisher scale, World Federation of Neurosurgical Surgeons scale, aneurysm site, surgical or endovascular treatment, decompressive craniectomy, vasospasm, infection (meningitis and pneumonia), presence of motor deficit, length of stay in the ICU, length of hospital stay, number of days under ventilator support, d-dimer at hospitalization, and the time to thromboprophylaxis (days). RESULTS:The univariate analysis showed that intraparenchymal cerebral hemorrhage, d-dimer at hospitalization, the time to thromboprophylaxis, motor deficit, and aneurysm located at the internal carotid artery were statistically significant factors. Intraparenchymal cerebral hemorrhage (OR 2,78 95%CI 1.07-7.12), motor deficit (OR 3.46; 95%CI 1.37-9.31), and d-dimer at hospitalization (OR 1.002 95% CI 1.001-1.003) were demonstrated as independent risk factors for deep-vein thrombosis. Length of hospital stay was also found to be significantly longer in patients who developed deep-vein thrombosis (p value 0.018). CONCLUSION:Elevated d-dimer level at the time of hospitalization, motor deficit, and the presence of an intraparenchymal hemorrhage are independent risk factors for deep-vein thrombosis. Patients with DVT also had a significantly longer hospital stay. Even though further studies are needed, patients with elevated d-dimer at hospitalization and intraparenchymal cerebral hemorrhage may benefit from a more aggressive screening strategy for deep-vein thrombosis.