Elevated Factor VIII and von Willebrand Factor Levels Predict Unfavorable Outcome in Stroke Patients Treated with Intravenous Thrombolysis

Abstract

IntroductionPlasma factor VIII (FVIII) and von Willebrand factor (VWF) levels have been associated with the rate and severity of arterial thrombus formation and have been linked to outcomes following thrombolytic therapy in acute myocardial infarction patients. Here, we aimed to investigate FVIII and VWF levels during the course of thrombolysis in acute ischemic stroke (AIS) patients and to find out whether they predict long-term outcomes.Materials and methodsStudy population included 131 consecutive AIS patients (median age: 69 years, 60.3% men) who underwent i.v. thrombolysis with recombinant tissue plasminogen activator (rt-PA). Blood samples were taken on admission, 1 and 24 h after rt-PA administration to measure FVIII activity and VWF antigen levels. Neurological deficit of patients was determined according to the National Institutes of Health Stroke Scale (NIHSS). ASPECT scores were assessed using computer tomography images taken before and 24 h after thrombolysis. Intracranial hemorrhage was classified according to the European Cooperative Acute Stroke Study (ECASS) II criteria. Long-term functional outcome was determined at 90 days after the event by the modified Rankin scale (mRS).ResultsVWF levels on admission were significantly elevated in case of more severe AIS [median and IQR values: NIHSS <6:189.6% (151.9–233.2%); NIHSS 6–16: 199.6% (176.4–250.8%); NIHSS >16: 247.8% (199.9–353.8%), p = 0.013]; similar, but non-significant trend was observed for FVIII levels. FVIII and VWF levels correlated well on admission (r = 0.748, p < 0.001) but no significant correlation was found immediately after thrombolysis (r = 0.093, p = 0.299), most probably due to plasmin-mediated FVIII degradation. VWF levels at all investigated occasions and FVIII activity before and 24 h after thrombolysis were associated with worse 24 h post-lysis ASPECT scores. In a binary backward logistic regression analysis including age, gender, high-sensitivity C-reactive protein, active smoking, diabetes, and NIHSS >5 on admission, elevated FVIII and VWF levels after thrombolysis were independently associated with poor functional outcomes (mRS ≥ 3) at 90 days (immediately after thrombolysis: FVIII: OR: 7.10, 95% CI: 1.77–28.38, p = 0.006, VWF: OR: 6.31, 95% CI: 1.83–21.73, p = 0.003; 24 h after thrombolysis: FVIII: OR: 4.67, 95% CI: 1.42–15.38, p = 0.011, VWF: OR: 19.02, 95% CI: 1.94–186.99, p = 0.012).ConclusionElevated FVIII activity and VWF antigen levels immediately after lysis and at 24 h post-therapy were shown to have independent prognostic values regarding poor functional outcomes at 90 days.

Extensive Catastrophic Thromboses from Elevation of Factor VIII

“… 4 While studies show a correlation of elevated factor VIII with thrombotic events, our case depicts a severe care of TS due to elevated factor VIII associated thrombotic coagulopathy. 6 …”

Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke

“…Regarding ischemic stroke patients who underwent thrombolysis, a study found that having elevated FVIII levels, both immediately and 24 hours after thrombolysis, led to a higher risk for poor functional outcome (mRS ≥ 3) at 90 days. 25 There have been some important recent developments regarding hemostatic factors in the context of first stroke that may also inform future treatment strategies in the context of secondary prevention. For instance, FXI appears to be a stronger risk factor for first ischemic stroke than myocardial infarction 26 and may therefore be a particularly attractive target.…”

PAI‐1 5G/5G genotype is an independent risk of intracranial hemorrhage in post‐lysis stroke patients

“…As at the time of patient enrollment mechanical thrombectomy was not yet available, none of the patients received such treatment. Baseline characteristics of the patient cohort have been published earlier . The presence of IS was diagnosed based on clinical symptoms, brain imaging using non‐contrast computerized tomography (NCCT) scan, and CT angiography (CTA).…”