Hemostatic Therapies For Acute Spontaneous Intracerebral Hemorrhage

Abstract

Cochrane Corner Section Editor: Peter A.G. Sandercock, MA, DM, FRCPE Hemostatic Therapies For Acute Spontaneous Intracerebral Hemorrhage Zhe Kang Law, MRCP; Rustam Al-Shahi Salman, PhD; Philip M. Bath, FMedSci; Thorsten Steiner, MD; Nikola Sprigg, FRCP O utcome after spontaneous intracerebral hemorrhage (ICH) is worsened by hematoma growth, which occurs in up to one third of patients within 24 hours of onset. Early hemostatic therapy might improve outcome by limiting hema- toma growth. Objectives This updated review aimed to examine the efficacy and safety of individual classes of hemostatic therapies in adults with acute spontaneous ICH, according to the type of antithrom- botic drug taken immediately before ICH onset (ie, anticoagu- lant, antiplatelet, or none).1 Methods Search Methods We searched the Cochrane Stroke Trials Register, MEDLINE, EMBASE, reference list of articles, and international trial registers up to November 2017. Selection Criteria We included randomized controlled trials (RCTs) of any hemo- static intervention for acute spontaneous ICH, compared with placebo, open control, or an active comparator, reporting relevant clinical outcomes. Data Collection and Analysis Two authors independently extracted data, assessed risk of bias, and contacted corresponding authors of eligible RCTs for spe- cific data if they were not provided in the published report of an RCT. Main Results We included 12 RCTs involving 1732 participants. There were 7 RCTs of clotting factors versus placebo/control (1480 participants), 3 RCTs of antifibrinolytic drugs versus placebo/control (57 participants), 1 RCT of platelet transfu- sion versus control (190 participants) and 1 RCT of clotting factors versus fresh frozen plasma (5 participants). We could not include 2 eligible RCTs of clotting factors versus fresh frozen plasma because they presented aggregate data for ICH and other types of intracranial hemorrhage. In 1 RCT of platelet transfusion versus control for antiplatelet-related ICH, there was a significant increase in death or dependence (modified Rankin Scale score 4–6) at day 90 (70/97 versus 52/93; risk ratio 1.29; 95% confidence interval 1.04–1.61). There were no significant differences in death or depen- dency at day 90 for clotting factors versus placebo/control (risk ratio 0.87; 95% confidence interval 0.70–1.07; Figure) and antifibrinolytic drugs versus placebo/control (risk ratio 1.25; 95% confidence interval 0.57–2.75) for acute sponta- neous ICH. There was no significant difference in death at day 90 for clotting factors versus fresh frozen plasma for anticoagulant-related ICH (risk ratio 0.27; 95% confidence interval 0.02–3.74). Implications for Practice Platelet transfusion seems harmful in comparison to standard care for adults with antiplatelet-associated ICH. We were unable to draw firm conclusions about the efficacy and safety of clotting factors and antifibrinolytic drugs for acute sponta- neous ICH or clotting factors versus fresh frozen plasma for anticoagulant-related ICH. Implications for Research Although recombinant factor VIIa does not seem beneficial based on existing evidence, RCTs of its use in patients with ICH and a spot sign on computed tomographic angiography are awaited (URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00810888 and NCT01359202). There are 6 ongoing RCTs of antifibrinolytic drugs in ICH. The superiority of clotting factors compared with fresh frozen plasma in improving clinical outcome needs to be estab- lished despite superiority in normalization of coagulation in the RCTs that we could not include. There is a need to distinguish between ICH and other intracranial hemorrhage while recruiting and reporting results in future trials of hemostatic therapies. Disclosures