Hemostatic Activation and Outcome After Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke

Abstract

for the NINDS rtPA Stroke Study Group Background and Purpose-Early thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rtPA) improves clinical outcome in acute ischemic stroke (AIS), but impaired endogenous fibrinolysis, thrombin generation, and vascular injury may hamper the efficacy of thrombolysis. We investigated in an exploratory, post hoc analysis the relationship between hemostatic markers and clinical outcomes among patients included in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study. Methods-Tissue plasminogen activator (tPA) antigen, thrombin-antithrombin complex (TAT), soluble thrombomodulin, and fibrinogen levels were measured in patients with AIS included in the NINDS rtPA Stroke Study from plasma samples collected at baseline, at 2 hours after treatment, and after 24 hours. Results-TAT and tPA antigen levels peaked at 2 hours selectively in the rtPA treatment group, whereas fibrinogen levels dropped at 2 hours and remained low after 24 hours (PϽ0.0001 for interaction effects between time and treatment). At 24 hours, higher levels of tPA antigen were associated with a lower chance of favorable outcome (odds ratio [OR]ϭ0.34; 95% CI, 0.14 to 0.82) selectively in the rtPA group, and higher levels of TAT (ORϭ1.72; 95% CI, 1.26 to 2.34) in the entire cohort and of thrombomodulin selectively in the rtPA group (ORϭ4.45; 95% CI, 1.26 to 15.67) were associated with higher 3-month mortality. Conclusions-Hemostatic activation after AIS appears to be independently associated with clinical outcome in patients treated with rtPA. However, because we have tested for multiple associations, some may have been identified by chance alone and require further confirmatory studies. On the basis of this exploratory analysis, there is a rationale to investigate the safety and efficacy of protocols in which rtPA is complemented by agents that are antithrombotic and enhance fibrinolysis. (Stroke. 2006;37:1798-1804.)

Change in Hemostatic Markers After Recombinant Tissue-Type Plasminogen Activator Is Not Associated With the Chance of Recanalization

“…8 Finally, a recent study found an association between hemostatic activation and clinical outcome. 3 Although we also found a dynamic change in these hemostatic markers, we were unable to find an association between the level of these markers and the likelihood of recanalization. One limitation of our study is the small sample of patients.…”

“…1,2 One hypothesis is that efficient recanalization is likely only if certain changes in hemostatic levels are achieved in comparison with baseline levels. A recently reported study suggested that hemostatic activation is associated with clinical outcome in patients treated with intravenous rtPA, 3 although no data about vascular patency was provided.…”

Guidelines for the Early Management of Patients With Acute Ischemic Stroke

“…[671][672][673][674][675] A higher hematocrit is associated with reduced reperfusion, greater infarct size, and higher mortality among patients after ischemic stroke. 671,674 Hemodilution and volume expansion are proposed as treatment options to reduce the viscosity of blood, improve flow through collateral channels and microvascular circulation, and increase oxygen-carrying capacity.…”

Cilostazol Reduces the Risk of Hemorrhagic Infarction After Administration of Tissue-Type Plasminogen Activator in a Murine Stroke Model

“…10,11 Reocclusion after tPA treatment is induced, at least in part, by the activation of the coagulation cascade by tPA. 12,13 These findings indicate that the use of antiplatelet drugs is potentially a double-edged sword in the context of tPA treatment; that is, use of antiplatelet agents is likely to be beneficial for stroke outcome despite increased risk of hemorrhagic infarction. Consistent with these findings, a randomized controlled trial in the Netherlands has shown that thrombolysis in combination with antiplatelet drugs prevented reocclusion and improved the clinical outcome.…”