Published Online
on February 23, 2006

A more recent version of this article appeared on April 1, 2006

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Submitted on December 12, 2005
Accepted on January 9, 2006

Pretreatment Hemostatic Markers of Symptomatic Intracerebral Hemorrhage in Patients Treated With Tissue Plasminogen Activator

Dolores Cocho MD^*; Montserrat Borrell PhD; Joan Martí-Fàbregas MD, PhD; Joan Montaner MD, PhD; Mar Castellanos MD, PhD; Yolanda Bravo MD; Laura Molina-Porcel MD; Roberto Belvís MD, PhD; Jorge-Alberto Díaz-Manera MD; Alejandro Martínez-Domeño MD; María Martínez-Lage MD; Mónica Millán MD; Jordi Fontcuberta MD, PhD; and Josep-Lluis Martí-Vilalta MD, PhD

From the Departments of Neurology (D.C., J.M.-F., Y.B., L.M.-P., R.B., J.-A.D.-M., A.M.-D., M.M.-L., J.-L.M.-V.) and Hematology (M.B., J.F.) Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Neurology (J.M.), Hospital Vall d'Hebrón. Barcelona, Spain; Department of Neurology (M.C.), Hospital Doctor Josep Trueta. Girona, Spain; and Department of Neurology (M.M.), Hospital Germans Trias i Pujol, Badalona, Spain.

^* To whom correspondence should be addressed. E-mail: dcocho{at}santpau.es.

Background and Purpose--Symptomatic intracerebral hemorrhage (ICH) is a major complication of thrombolysis in patients with acute ischemic stroke. We analyzed whether baseline hemostatic markers could predict symptomatic ICH (SICH).

Methods--In a multicenter study of patients treated with intravenous tissue plasminogen activator (t-PA) within 3 hours of stroke onset, we analyzed the following variables: demographic data, vascular risk factors, blood glucose at admission, time from the onset of symptoms to t-PA infusion, blood pressure, neurological deficit measured by the National Institutes of Health Stroke Scale (NIHSS) score, early signs of ischemia on the baseline computed tomography (CT) scan, and protocol deviations. In blood samples, the following markers of coagulation/fibrinolysis were measured before treatment: fibrinogen, prothrombin fragments 1+2, Factor XIII, Factor VII, ₂ antiplasmin, plasminogen activator inhibitor-1 (PAI-1), and thrombin-activatable fibrinolysis inhibitor. ICH was classified according to the European Cooperative Acute Stroke Study (ECASS) II criteria. SICH was defined as a parenchymal hematoma-1 (PH1) or PH2 type, associated with an increase in 4 points on the NIHSS score appearing within 36 hours after infusion.

Results--We studied 114 patients. Mean age was 68.4±12.7 years, and 61% were men. The median baseline NIHSS score was 14. Mean time to treatment was 153±33 minutes. Eight patients had SICH (7%), and 18 patients (15.7%) had asymptomatic ICH. None of the baseline markers of coagulation/fibrinolysis were associated with SICH. In the multivariate analysis, only NIHSS on admission was an independent risk factor for SICH.

Conclusions--None of the hemostatic markers analyzed in our study predicted symptomatic cerebral hemorrhage in patients with ischemic stroke treated with t-PA.

Key words: hemorrhage • hemostatics • thrombolysis

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