Clotting Factors to Treat Thrombolysis-related Symptomatic Intracranial Hemorrhage in Acute Ischemic Stroke

Abstract

Background Symptomatic intracranial hemorrhage (sICH) occurs uncommonly after ischemic stroke therapy with Tissue plasminogen activator (TPA). Clotting factor administration may be a treatment option. Objective To determine if treatment with clotting factors was associated with improved outcomes in sICH. Methods We conducted a retrospective cohort study within University of Texas at Houston Stroke registry involving consecutive patients from February 1, 2007 to June 30, 2011 with TPA related sICH; including cases with subsequent intra-arterial therapy. Intervention clotting factor administration; fresh frozen plasma or cryoprecipitate. Outcomes modified Rankin Score mRS at discharge, death, and hematoma expansion. Results Of 921 patients treated with TPA, 48 (5.2%) had sICH and 45 met criteria for the study. Nineteen patients received clotting factors (42.2%) (18 received FFP and 7 received cryoprecipitate), while 26 (57.8%) patients received conservative management without clotting factors. None of the patients treated with clotting factors and only 2 of those who did not receive clotting factors had a good outcome; mRS ≤2. All the patients treated with clotting factors and most of those not treated were left bedridden or dead (mRS 4–6); 19 (100%) vs. 22 (85%). Mortality was 9 (47.4%) vs. 9 (34.6%) respectively. There was no difference in hematoma expansion between the two groups. Conclusions We found no evidence that treatment of sICH with clotting factors has a favorable effect on clinical or radiological outcomes. However, the sample was small due to the low frequency of sICH. New treatments are urgently needed for this uncommon yet serious condition.

Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

“…Existing studies of hemorrhage expansion after thrombolysis typically include only sICH and thus are weighted toward PH-2. Only 1 study considered radiographic type 83 and found that PH-2 represented ≈64% of sICH cases, but it could not clarify any differential risk of sICH expansion. Therefore, there is no evidence that different appearance of hemorrhage influences opportunity to benefit from treatment.…”

“…48,83,84 In 1 study of 128 alteplase-treated patients, nearly 80% of patients with sICH were diagnosed >2 hours after the alteplase infusion, and the median time from alteplase treatment to sICH diagnosis was nearly 8 hours. 48 Therefore, treating practitioners may consider extending the period of intensive (every 30 minutes) neurological and cardiovascular monitoring to 12 hours from the currently recommended 8 hours, particularly in patients with high risk for developing sICH.…”

“…However, clinically relevant hemorrhage expansion consistently occurred in 30% to 40% of patients diagnosed with sICH across these studies. 48,83,84,91 Radiographic Appearance It is unclear whether type of ICH (HI-1, HI-2, PH-1, PH-2, subarachnoid hemorrhage, or subdural hemorrhage) affects the risk of expansion. Existing studies of hemorrhage expansion after thrombolysis typically include only sICH and thus are weighted toward PH-2.…”

“…83 Thus, it is unclear whether sICH is presaged by asymptomatic hemorrhage with a time window wide enough for both diagnosis and treatment to influence outcome. In theory, the risk of hemorrhage expansion may be greater for an asymptomatic hemorrhage in the setting of both alteplase and mechanical thrombectomy, especially if successful recanalization is achieved or the mechanism of hemorrhage involves blood vessel perforation or endothelial injury related to the neurointerventional procedure.…”

“…Once the diagnosis is made, predictors of death include poor neurological examination, large hematoma volume, and withdrawal of care. 48,83,92 It may be that small amounts of blood are not clinically relevant, and large hematoma volumes have such poor outcomes that treating any coagulopathy can offer no benefit.…”