Thromboembolic risks of recombinant factor VIIa Use in warfarin-associated intracranial hemorrhage: a case–control study

Abstract

BackgroundRecombinant factor VIIa (rFVIIa) may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH), FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP) and vitamin K alone.MethodsWe identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts.ResultsBoth rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%), deep venous thrombosis (DVT) or pulmonary embolism (PE) (22% vs 18%), coronary artery disease (CAD) (38% vs 32%), and abnormal electrocardiogram (EKG) (78% vs 85%). Troponin elevation following wICH was prevalent in both groups (47% vs 41%). Clinically significant myocardial infarction (MI), defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52). Past history of CAD (p=0.0061) and baseline abnormal EKG (p=0.02) were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18) and ischemic stroke (2% vs 0%; p=0.38) were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001) and 6 hours (p<0.0001) and received fewer units of FFP transfusion (3 vs 5; p=0.003).ConclusionsPre-existing thromboembolic risk factors as well as post-hemorrhage troponin elevation are prevalent in wICH patients. Clinically significant MI occurs in up to 13% of wICH patients. rFVIIa use was not associated with increased incidence of clinically significant MI or other venous or arterial thromboembolic events in this wICH cohort.

Recombinant factor VIIa use in patients presenting with intracranial hemorrhage

“…It also showed that the INR reversal comes with no significant risk of thromboembolic complications. This conclusion is corroborated by other studies that have also investigated the safety of rFVIIa for warfarin patients (Deveras and Kessler 2002 ; DeLoughery et al 2013 ; H-Y et al 2012 ). To our knowledge, this is one the largest retrospective reviews looking specifically at the use of rFVIIa administration for patients in need of emergent neurosurgical intervention.…”

“…rFVIIa is known to rapidly normalize INR in warfarin-associated systemic bleeding but whether such INR normalization reflects full reversal of coagulopathy remains controversial (H-Y et al 2012). Twenty percent of patients in our study received a dose of rFVIIa less than 50 mcg/kg which is considered low dosing of rFVIIa.…”

“…The most effective dose for warfarin reversal has not been established, but clinical trials have published doses ranging from 15–90 mcg/kg (Deveras and Kessler 2002 ). rFVIIa is known to rapidly normalize INR in warfarin-associated systemic bleeding but whether such INR normalization reflects full reversal of coagulopathy remains controversial (H-Y et al 2012 ). Twenty percent of patients in our study received a dose of rFVIIa less than 50 mcg/kg which is considered low dosing of rFVIIa.…”

The use of activated recombinant factor VII in neurosurgery

“…Связаны они, прежде всего, с его основным эффектом -генерацией «тромбинового взрыва» в месте повреждения сосудистой стенки, т.е. относятся к тромботическим [87,88]. Анализ этой проблемы показал, что, действительно, клиническое применение rFVIIa связано с повышенным риском тромботических осложнений у пациентов вне ситуации массивной кровопотери и выраженной гипокоагуляции (ЧМТ, ВМК).…”

“…Анализ этой проблемы показал, что, действительно, клиническое применение rFVIIa связано с повышенным риском тромботических осложнений у пациентов вне ситуации массивной кровопотери и выраженной гипокоагуляции (ЧМТ, ВМК). При этом на фоне применения препарата возрастает, главным образом, частота артериальных, а не венозных тромбозов, а основным контингентом являются пациенты старше 70 лет [87][88][89]. Исходя из механизма действия rFVIIa, который реализуется только в месте контакта с тканевым фактором (т.е.…”