Protamine, Platelet Function and Coagulation in Cardiac Surgery

Bleeding is a serious and common complication in cardiac surgery. Complicated surgery together with alterations in hemostatic conditions from the use of cardiopulmonary bypass (CPB), presents challenges in how to preserve hemostasis in the patient. CPB is thought to affect platelet function and coagulation in many ways. Before connecting the patient to the CPB system, heparin is used as anticoagulation. With the connection between the patient and the CPB tubing there is a dilution of platelets and coagulation proteins and despite anticoagulation there is an activation of coagulation and inflammation resulting in consumption of coagulation factors and triggering of fibrinolysis. After disconnection of the CPB system, protamine is used to reverse the effect of heparin and restore the coagulation capacity of the patient. When protamine binds to heparin, the anticoagulant effect of heparin is removed but protamine is known to affect both platelet function and coagulation. There is uncertainty about how to best dose protamine to limit the negative effects from protamine without risking remaining heparin effect. A lot is known about how and to what extent cardiac surgery with the use of CPB affect the hemostasis in the patient, but there are still many uncertainties. The aims of this thesis were to examine how platelets are affected by CPB and protamine and to investigate if dosing of protamine had an impact on the risk of remaining or reappearing heparin after cardiac surgery. We also wanted to investigate whether sampling site matters when studying platelet function. In paper I, we found that protamine in vitro interacts with platelets by both a direct activating effect and by a secondary impairment of function when exposed to other activators. The impairment of platelet function from protamine could also be seen in vivo and is described in paper III. In paper III, we also conclude that, in contrast to prior studies, there was no increase in activation in pla