Systematic Review and Meta-Analysis of Thromboprophylaxis with Heparins Following Intracerebral Hemorrhage

Gerald Chi; Jane J. Lee; Shi Sheng; Jolanta Marszalek; Michael L. Chuang

doi:10.1055/s-0042-1744541

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2022; 122(07): 1159-1168
DOI: 10.1055/s-0042-1744541

Stroke, Systemic or Venous Thromboembolism

Systematic Review and Meta-Analysis of Thromboprophylaxis with Heparins Following Intracerebral Hemorrhage

Gerald Chi

¹Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States

,

Jane J. Lee

²Department of Trial Design and Development, Baim Institute for Clinical Research, Boston, Massachusetts, United States

,

Shi Sheng

³Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China

,

Jolanta Marszalek

⁴Department of Neurology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States

,

Michael L. Chuang

¹Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States

› Author Affiliations

Abstract

Background The efficacy and safety of pharmacological thromboprophylaxis in patients with intracerebral hemorrhage (ICH) remains unclear.

Methods A literature search was performed to collect studies comparing the effect of thromboprophylaxis in patients with ICH. The primary endpoints were deep vein thrombosis (DVT), pulmonary embolism (PE), and hematoma expansion or rebleeding. A meta-analytic approach was employed to estimate the relative risk (RR) by fitting fixed-effects (FE) and random-effects (RE) models.

Results A total of 28 studies representing 3,697 hospitalized patients with ICH were included. Thromboprophylaxis was initiated within 4 days following hospital presentation and continued for 10 to 14 days in most of studies. Compared with control, thromboprophylaxis was associated with a reduced risk of DVT (47/1,399 [3.4%] vs. 202/1,377 [14.7%]; FE: RR, 0.24; 95% CI, 0.18–0.32; RE: RR, 0.27; 95% CI, 0.19–0.39) as well as PE (9/953 [0.9%] vs. 37/864 [4.3%]; FE: RR, 0.33; 95% CI, 0.19–0.57; RE: RR, 0.37; 95% CI, 0.21–0.66). Thromboprophylaxis was not associated with increased risk of hematoma expansion or rebleeding (32/1,319 [2.4%] vs. 37/1,301 [2.8%]; FE: RR, 0.75; 95% CI, 0.48–1.18; RE: RR, 0.80; 95% CI, 0.49–1.30) or mortality (117/925 [12.6%] vs. 139/904 [15.4%]; FE: RR, 0.82; 95% CI, 0.65–1.03; RE: RR, 0.83; 95% CI, 0.66–1.04).

Conclusion Thromboprophylaxis was effective in preventing DVT and PE without increasing the risk of hematoma expansion or bleeding among ICH patients. Future studies should explore the long-term effects of thromboprophylaxis in this population, particularly on the functional outcomes.

Keywords

intracerebral hemorrhage - hemorrhagic stroke - pulmonary embolism - heparin

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References

References
1 Otite FO, Khandelwal P, Malik AM, Chaturvedi S, Sacco RL, Romano JG. Ten-year temporal trends in medical complications after acute intracerebral hemorrhage in the United States. Stroke 2017; 48 (03) 596-603
2 Hemphill III JC, Greenberg SM, Anderson CS. et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015; 46 (07) 2032-2060
3 Paciaroni M, Agnelli G, Venti M, Alberti A, Acciarresi M, Caso V. Efficacy and safety of anticoagulants in the prevention of venous thromboembolism in patients with acute cerebral hemorrhage: a meta-analysis of controlled studies. J Thromb Haemost 2011; 9 (05) 893-898
4 Cherian LJ, Smith EE, Schwamm LH. et al. Current practice trends for use of early venous thromboembolism prophylaxis after intracerebral hemorrhage. Neurosurgery 2018; 82 (01) 85-92
5 Prabhakaran S, Herbers P, Khoury J. et al. Is prophylactic anticoagulation for deep venous thrombosis common practice after intracerebral hemorrhage?. Stroke 2015; 46 (02) 369-375
6 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372 (71) n71
7 Sterne JAC, Savović J, Page MJ. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898
8 Sterne JA, Hernán MA, Reeves BC. et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016; 355: i4919
9 McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods 2021; 12 (01) 55-61
10 Marszalek J, Mehrsefat S, Chi G. The risk of stroke among acutely ill hospitalized medical patients: lessons from recent trials on extended-duration thromboprophylaxis. Expert Rev Hematol 2017; 10 (08) 679-684
11 Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22 (04) 719-748
12 Paule RC, Mandel J. Consensus values, regressions, and weighting factors. J Res Natl Inst Stand Technol 1989; 94 (03) 197-203
13 Higgins JP, Thompson SG, Spiegelhalter DJ. A re-evaluation of random-effects meta-analysis. J R Stat Soc Ser A Stat Soc 2009; 172 (01) 137-159
14 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21 (11) 1539-1558
15 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315 (7109): 629-634
16 Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J Clin Epidemiol 2008; 61 (10) 991-996
17 Schwarzer G, Schwarzer MG. Package ‘meta’. Vienna: The R Foundation for Statistical Computing; 2012: 9
18 Dickmann U, Voth E, Schicha H, Henze T, Prange H, Emrich D. Heparin therapy, deep-vein thrombosis and pulmonary embolism after intracerebral hemorrhage. Klin Wochenschr 1988; 66 (23) 1182-1193
19 Wasay M, Khan S, Zaki KS. et al. A non-randomized study of safety and efficacy of heparin for DVT prophylaxis in intracerebral haemorrhage. J Pak Med Assoc 2008; 58 (07) 362-364
20 Li L, Poon MTC, Samarasekera NE. et al. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol 2021; 20 (06) 437-447
21 Murthy SB, Gupta A, Merkler AE. et al. Restarting anticoagulant therapy after intracranial hemorrhage: a systematic review and meta-analysis. Stroke 2017; 48 (06) 1594-1600
22 So SC. SoSTART Collaboration. Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage in the UK: a randomised, open-label, assessor-masked, pilot-phase, non-inferiority trial. Lancet Neurol 2021; 20 (10) 842-853
23 Kananeh MF, Fonseca-Paricio MJ, Liang JW. et al. Ultra-early venous thromboembolism (VTE) prophylaxis in spontaneous intracerebral hemorrhage (sICH). J Stroke Cerebrovasc Dis 2021; 30 (02) 105476
24 Hull RD, Schellong SM, Tapson VF. et al; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010; 153 (01) 8-18
25 Siironen J, Juvela S, Varis J. et al. No effect of enoxaparin on outcome of aneurysmal subarachnoid hemorrhage: a randomized, double-blind, placebo-controlled clinical trial. J Neurosurg 2003; 99 (06) 953-959
26 Wurm G, Tomancok B, Nussbaumer K, Adelwöhrer C, Holl K. Reduction of ischemic sequelae following spontaneous subarachnoid hemorrhage: a double-blind, randomized comparison of enoxaparin versus placebo. Clin Neurol Neurosurg 2004; 106 (02) 97-103

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Supplementary Material