Abstract 5249

TAFI (thrombin-activated fibrinolysis inhibitor) and PAI-1 play important roles in fibrinolysis, as they both reduce plasmin generation; PAI-1 a 50 KDa glycoprotein is a serine-proteinase inhibitor; TAFI is a 55 KDa plasma zymogen that is activated by either plasmin/thrombin or thrombin/thrombomodulin complex into an active carboxypeptidase, in particular, it is a basic zinc dependent metallo-carboxipeptidase specific for C-terminal lysine and arginine residue inhibiting degradation of the fibrin clot.

We investigated the influence of PAI-1 and TAFI levels on stroke by determining their plasmatic antigen concentration by an electro-immunoassay. We found that PAI-1 levels are increased during the early stage of stroke and that it may also predict clot lysis resistance in patients treated with trombolysis (38.8 ng/ml +/− 14.6, p <0.0001) compared with control subjects (16.2 ng/ml +/−6.8, p <0.0001); TAFI levels were significantly higher in patient with stroke (184.8 nmol/l +/− 62.6 nmol/l), than in healthy control subjects (102.4 nmol/l +/− 36.4 nmol/l, p <0.0001). We have observed that a combination of both PAI-1 higher than 24.6 mg/ml (OR: 12.8. CI: 1.16 to 134.2), and TAFI higher than >180 nmol/l (OR.12.9 CI 1.42 to 116.6), had a sensibility of 92.2%, and a specificity of 98.4% in predicting stroke. The analysis of these results showed that TAFI antigen levels higher than 180nmo/L combined with PAI-1 levels higher than 24 mg/ml are a strong risk factor for clot lysis, stroke (for the evolution, severity, and outcome) and showed a potentially attractive target for fibrinolytic therapies.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
carboxypeptidase u, cerebrovascular accident, ischemic stroke, plasminogen activator inhibitor 1, thrombin, plasmin, antigen assay, antigens, arginine, carboxypeptidase
© 2011 by The American Society of Hematology
2011
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