Relative contributions of collagen and tissue factor to thrombus formation on damaged vascular vessels: in-vitro studies with circulating blood.

BACKGROUND AND OBJECTIVE

Thrombogenicity of ruptured atherosclerotic plaques is mainly attributed to the exposure of collagen (Col) and tissue factor (TF). Using in-vitro approaches, we explored the relative contribution of Col and TF to local thrombogenesis.

METHODS

Surfaces coated with Col and human TF, alone or in combinations (diluted Col on TF, and diluted TF on Col), were exposed to flowing blood at a shear rate of 600/s. Platelet and fibrin deposition were analyzed morphometrically. Generation of prothrombin fragments (F1+2) was determined as a measure of global activation of coagulation.

RESULTS

Col and TF alone behaved as adhesive substrata to platelets supporting similar platelet coverage around 22%. Col induced tight aggregates, whereas TF promoted adhesive events. In studies with combinations of Col and TF, platelet aggregation was always enhanced with statistical elevations of the thrombus area (P<0.05). Generation of F1+2 was surface-dependent and was at its highest levels when both proteins were combined (P<0.05). However, local fibrin formation was statistically increased in surfaces containing lower concentrations of TF on Col (P<0.01 vs. overall surfaces assessed).

CONCLUSION

Our studies show that combinations of Col and TF always enhance thrombogenesis, but small amounts of TF on Col surfaces resulted in the most procoagulant combination. The present results suggest that plaques exposing high contents of Col, with small amounts of TF, would provide the most occlusive combination.