Safety of Prophylactic Heparin in the Prevention of Venous Thromboembolism After Spontaneous Intracerebral Hemorrhage: A Meta-analysis

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: intracerebral hemorrhage, stroke, hemorrhagic stroke, subarachnoid hemorrhage, heparin, heparinoids, low-molecular-weight heparin, anticoagulants, prophylactic, low dose, prevention, deep venous thrombosis, pulmonary embolism, venous thrombosis, randomized controlled trial, controlled clinical trial, and outcome. 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.