Effects of the platelet-activating factor receptor antagonist WEB 2086 on whole blood coagulation and fibrinolysis in a thromboelastography assay

The effects of WEB 2086 on human blood coagulation and fibrinolysis were studied in vitro using computerized thromboelastography and native whole blood. WEB 2086 (3.0, 30, 150, and 300 mu M) had no apparent effect on the split point (SP), reaction time (R) and lysis of the clot. The biKoatugulierung time (K) was prolonged, the angle (alpha) and maximum amplitude (MA) were diminished, and the overall coagulation index (TEG index) was smaller. SP and R indicate onset of coagulation with the formation of fibrin strands, suggesting that WEB 2086 had no effect on the plasma factors. Since the Lysis parameter reflects fibrinolysis, WEB 2086 had no demonstrable fibrinolytic activity. K,cr and MA involve platelet function and the integrity of fibrin; the fact that these factors were affected to the exclusion of SP and R suggests an effect largely on platelets. There was lack of a dose-response relationship at this concentration range (3.0-300 mu M), probably due to saturation of PAF receptors even at the lowest effective concentration. These findings are consistent with the known effects of WEB 2086 on platelet function and suggest that thromboelastography may be a useful tool in the study of the activity of PAF receptor antagonists on coagulation profiles. Furthermore, since WEB 2086 is a highly specific PAF receptor antagonist devoid of intrinsic activity, and the samples used were not treated with exogenous PAF, these results suggest that endogenous PAF may play a significant role in the normal clotting mechanism.