Contact between a polymer and whole blood: Sequence of events leading to thrombin generation

The mechanism by which thrombin is generated on a polymer surface in an ext racorporeal circuit is not yet fully understood. To address this question w e have developed an in vitro chamber model in which whole blood containing heparin (I IU/mL) comes in contact with a commonly used biomaterial, polyvi nyl chloride (PVC). Incubation of blood in the chamber for 60 minutes at 37 degreesC resulted in the binding of platelets to the material surface and the generation of thrombin-antithrombin complexes. Corn trypsin inhibitor, a specific inhibitor of factor XIIa, inhibited this thrombin-antithrombin c omplex generation in blood in contact with PVC, which is not considered an efficient activator of factor XII. The addition of the glycoprotein IIb/III a inhibitor Ro44-9883 abrogated platelet binding and aggregation and result ed in decreased generation of thrombin-antithrombin complexes. Thrombin-ant ithrombin generation was also negligible in platelet-rich plasma but could be partially restored in the presence of erythrocytes. Taken together, thes e data are compatible with a model in which thrombin generation is triggere d by factor XII. The response to contact with PVC appears to begin with a l ow-grade generation of thrombin that involves both erythrocytes and leukocy tes and that activates platelets, followed by the activation of a platelet- dependent amplification loop that produces most of the thrombin.