fibrinopeptide-a and Brain-Ischemia

The association between hemostatic activation, stroke mechanism, and outcome is poorly defined. The Hemostatic System Activation Study (HAS) investigators measured serial levels of prothrombin fragment F1.2, a marker of thrombin generation, in patients enrolled in the Warfarin Aspirin Recurrent Stroke Study (WARSS).. HAS enrolled 631 of the 2,206 patients in WARSS. Strokes were subtyped according to inferred mechanism. Plasma was collected for F1.2 at randomization (within 30 days of stroke), 3 months, 12 months, and 18 months. The 3 to 6 month samples in aspirin-treated patients were used for the primary analysis.. The authors analyzed 3 to 6 month samples on 320 patients. Higher F1.2 levels were associated with older age, female sex, and hypertension. There was no difference between mean F1.2 levels in 56 cryptogenic (0.9 +/- 0.32 nmol/L) and 114 non-cryptogenic (1.13 +/- 0.74 nmol/L) patients or across specific stroke subtypes. There was an 8.8%/year (p = 0.006) increase in mean F1.2 levels. There was a trend toward higher risk of recurrent stroke or death as F1.2 levels increased in aspirin (RR: 1.30, 95% CI: 0.57 to 2.94, p = 0.53) and warfarin treated patients (RR: 1.68, 95% CI: 0.48 to 5.94, p = 0.42). F1.2 levels were reduced on average 70% in warfarin-treated patients in a dose-dependent fashion.. F1.2 levels did not appear to differ by stroke subtype, suggesting that factors other than underlying stroke pathophysiology influence thrombin generation in the post-acute stroke period. F1.2 levels were suppressed by warfarin in a dose-dependent fashion. Additional research is needed to determine the predictive value of F1.2 after stroke.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Biomarkers; Brain Infarction; Brain Ischemia; Cohort Studies; Comorbidity; Female; Fibrinopeptide A; Follow-Up Studies; Humans; International Normalized Ratio; Intracranial Thrombosis; Male; Middle Aged; Multicenter Studies as Topic; Peptide Fragments; Prothrombin; Randomized Controlled Trials as Topic; Recurrence; Stroke; Thrombin; Warfarin

To evaluate the role of the coagulation and fibrinolysis abnormalities in the pathogenesis of ischemic stroke of undetermined etiology, we assayed plasma concentration of fibrinopeptide-A and thrombin-antithrombin III complex, both sensitive markers for thrombin activation and fibrin formation, and D-dimer, a marker of plasmin activity and fibrinolysis. Hemostatic markers were measured in 32 patients with acute stroke and 20 patients with chronic stroke, and compared with 21 normal subjects. Fibrinopeptide-A and thrombin-antithrombin III complex levels were not elevated significantly, whereas the D-dimer level was markedly raised in acute (p<0.001) and chronic (p<0.05) phases of ischemic stroke in comparison with the control group. Prolonged elevation of D-dimer concentration suggests that hemostatic abnormalities have a primary role in the pathogenesis of ischemic stroke. The measurement of D-dimer concentration may help to better decide the indications for therapy of the patients with ischemic stroke of undetermined etiology.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antithrombin III; Biomarkers; Brain Ischemia; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Hemostasis; Humans; Male; Middle Aged; Peptide Hydrolases; Thrombophilia

Twenty-seven young adults (mean age 46) with ischemic cerebrovascular disease (ICD) were reinvestigated about 5 years after discharge and compared to 67 healthy controls. Factor VIII related antigen was again found significantly (p less than 0.005 and p less than 0.001) increased in male as well as female patients and a significant (r = 0.66, p less than 0.001) correlation was found with earlier data. Factor VIII biological activity was again found increased, significantly (p less than 0.001) in males. In contrast to earlier results antithrombin antigen and activity were significantly (p less than 0.001) decreased in males. This finding and decreased levels of factor XII in female patients (p less than 0.001) and of prekallikrein in male patients (p less than 0.01) could reflect disturbed regulatory functions or possibly constitutional differences. As in most subjects no increase of fibrinopeptide A was found, there was no sign of continuous activation of the whole coagulation sequence. Since hemostatic abnormalities were unrelated to acute phase reacting proteins they were obviously of a different nature than unspecific response to tissue damage and acute stress. High levels of factor VIII and low levels of antithrombin imply that the coagulation system could be more easily activated when other factors coincide, e.g. intimal lesions in carotide arteries.

Topics: Acute Disease; Adult; Aged; Antigens; Antithrombins; Blood Coagulation; Blood Coagulation Factors; Brain Ischemia; Factor VIII; Factor XII; Female; Fibrinogen; Fibrinopeptide A; Follow-Up Studies; Humans; Kallikreins; Male; Middle Aged; Prekallikrein; Sex Factors; von Willebrand Factor