Markers of Coagulation and Fibrinolysis Predicting the Outcome of Acute Ischemic Stroke Thrombolysis Treatment: A Review of the Literature

Abstract

Intravenous administration of recombinant tissue plasminogen activator (rt-PA) has been proven to be safe and effective in the treatment of acute ischemic stroke. Little is known, however, why this treatment is less effective in some patients while in others life-threatening side-effects, e.g., symptomatic intracerebral hemorrhage might occur. Clinical failure of thrombolysis related to absent or partial recanalization or reocclusion as well as hemorrhagic complications of thrombolysis are possibly related to hemostatic events. Data on markers of coagulation and/or fibrinolysis in acute stroke patients are numerous and may provide indications regarding therapy outcomes. Better understanding of the hemostatic and fibrinolytic system during rt-PA therapy might be clinically useful and ultimately might lead to an improvement in the efficacy or safety of this treatment. Studies on thrombus composition retrieved from cerebral arteries may also advance our knowledge and provide a key to improve acute stroke therapy. Here we provide a comprehensive review on a wide range of factors and markers of coagulation and fibrinolysis that have been studied in the context of thrombolysis outcome in ischemic stroke patients. Moreover, a brief summary is given on the most recent research on thrombus composition having a potential influence on outcomes.

Keywords: coagulation; fibrinolysis; outcome; stroke; thrombolysis.

Figure 1

Simplified scheme demonstrating the main elements of coagulation, fibrinolysis, and thrombus formation, depicting publications that investigated the relationship of these elements with the outcome of thrombolytic therapy applied in acute ischemic stroke. α2PI, α2 plasmin inhibitor; FVII, factor VII; FVIIa, activated factor VII; FVIII, factor VIII; FVIIIa, activated factor VIII; FIXa, activated factor IX; FXIa, activated factor XI; FXIIa, activated factor XII; FXIII, factor XIII; FXIIIa, activated factor XIII; FXIII-A₂B₂, plasma (tetramer) form of factor XIII; PAI-1, plasminogen activator inhibitor-1; RBC, red blood cell; TAFI, thrombin-activatable fibrinolysis inhibitor TAFIa, activated thrombin-activatable fibrinolysis inhibitor; TAT complex, thrombin-antithrombin complex; TF, tissue factor; tPA, tissue plasminogen activator; VWF, von Willebrand Factor; WBC, white blood cell.