September 14, 2004
View Full PaperThrombin generation in non-cardioembolic stroke subtypes
Structured PICO
Do prothrombin fragment F1.2 levels differ by stroke subtype in patients with non-cardioembolic stroke?
P
Population
631 patients with non-cardioembolic stroke enrolled in the Hemostatic System Activation Study (HAS) sub-study of the Warfarin Aspirin Recurrent Stroke Study (WARSS). Primary analysis included 320 patients.
I
Intervention
Measurement of prothrombin fragment F1.2 levels
C
Comparator
Cryptogenic vs non-cryptogenic stroke subtypes
O
Outcome
Mean F1.2 levels at 3 to 6 monthssurrogate
Thrombin generation (F1.2 levels) does not differ by stroke subtype in the post-acute period of non-cardioembolic stroke, suggesting other factors influence hemostatic activation.
Abstract
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.