Plasma factor and inhibitor composition contributes to thrombin generation dynamics in patients with acute or previous cerebrovascular events.
BACKGROUND
More than 80% of cerebrovascular events are ischemic and largely thromboembolic by nature. We evaluated whether plasma factor composition and thrombin generation dynamics might be a contributor to the thrombotic phenotype of ischemic cerebrovascular events.


METHODS
We studied (1) 100 patients with acute ischemic stroke (n=50) or transient ischemic attack (TIA) (n=50) within the first 24 hours from symptom onset, and (2) 100 individuals 1 to 4 years following ischemic stroke (n=50) or TIA (n=50). The tissue factor pathway to thrombin generation was simulated with a mathematical model using plasma levels of clotting factors (F)II, V, VII, VIII, IX, X, antithrombin and free tissue factor pathway inhibitor (TFPI).


RESULTS
The plasma levels of free TFPI, FII, FVIII, and FX were higher, while antithrombin was lower, in the acute patients compared to the previous event group (all p≤0.02). Thrombin generation during acute events was enhanced, with an 11% faster maximum rate, a 15% higher maximum level and a 26% larger total production (all p<0.01). The increased thrombin generation in acute patients was determined by higher FII and lower antithrombin, while increased free TFPI mediated this effect. When the groups are classified by etiology, all stroke sub-types except cardioembolic have increased TFPI and decreased AT and total thrombin produced.


CONCLUSIONS
Augmented thrombin generation in acute stroke/TIA is to some extent determined by altered plasma levels of coagulation factors.
Gissel
Matthew
M
Department of Biochemistry, University of Vermont, Colchester, VT, USA.
Undas
Anetta
A
Slowik
Agnieszka
A
Mann
Kenneth G
KG
Brummel-Ziedins
Kathleen E
KE
D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000378:metabolism*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood* / Q000209:etiology; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000097:blood* / Q000209:etiology; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism
D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D013917:Thrombin