HEPARIN ABLATES FORCE DEVELOPMENT DURING PLATELET-MEDIATED CLOT RETRACTION

Although snake venom enzymes such as reptilase do not cause viscous me tamorphosis, platelet secretion or clot retraction; when batroxobin an d calcium are added to citrated blood significant platelet force devel opment occurs. When this batroxobin-calcium system was applied to the study of platelet function during cardiopulmonary bypass (CPB), force development was found to be completely inhibited. After heparin revers al by protamine sulfate, significant recovery of force occurred. The p resent investigation was performed to evaluate the role of heparin in reducing force development during CPB. At concentrations above 0.10 U/ ml, heparin totally suppressed force development in normal plasma. Add ition of protamine sulfate to heparinized plasma caused complete recov ery of force development. These concentrations of heparin had little e ffect on platelet aggregation by ADP or collagen. Possible direct effe cts of heparin on fibrin assembly and structure were studied by adding varying amounts of heparin to plasma and then inducing clot formation with batroxobin. At 1 U/ml, heparin reduced the size of fibrin fibers by 33%. Higher heparin concentrations had no additional effect. These results indicate that heparin may be responsible for a significant co mponent of the decreased platelet force noted during cardiopulmonary b ypass. To test whether heparin's effect could be due to suppression of thrombin activity, the effects of the antithrombin hirudin on force d evelopment were measured. Hirudin also inhibited force development in a concentration dependent manner. Thus, heparin's reduction of platele t force development may be due, at least in part, to suppression of th rombin activity.