Thrombin generation in non-cardioembolic stroke subtypes: the Hemostatic System Activation Study.
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.


CONCLUSIONS
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.
Furie
K L
KL
V.B.K. 802, Stroke Service, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA. kfurie@partners.org
Rosenberg
R
R
Thompson
J L
JL
Bauer
K
K
Mohr
J P
JP
Rosner
B
B
Sciacca
R
R
Barzegar
S
S
Thornell
B
B
Costigan
T
T
Kistler
J P
JP
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D020520:Brain Infarction / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D005344:Fibrinopeptide A / Q000032:analysis*; D005500:Follow-Up Studies; D006801:Humans; D019934:International Normalized Ratio; D020767:Intracranial Thrombosis / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010446:Peptide Fragments / Q000032:analysis*; D011516:Prothrombin / Q000032:analysis*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D020521:Stroke / Q000097:blood* / Q000145:classification / Q000188:drug therapy / Q000503:physiopathology; D013917:Thrombin / Q000096:biosynthesis*; D014859:Warfarin / Q000627:therapeutic use
D000925:Anticoagulants; D015415:Biomarkers; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D005344:Fibrinopeptide A; D014859:Warfarin; D011516:Prothrombin; D013917:Thrombin; D001241:Aspirin