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 platelets, nor net loss of platelets, during moderate CPB times. After CPB we found no impairment of platelet function compared with before surgery.  In paper II, we found no differences in platelet aggregability between venous and arterial blood when measured with impedance aggregometry. Also, with flow cytometry most of our parameters showed no differences between venous and arterial blood. However, there were some differences. For example, the level of monocyte-platelet-aggregates was higher in venous- compared with arterial blood, which raises questions whether platelet function changes with oxygenation and flow conditions.  In paper IV, we found a dose dependent risk of remaining heparin activity in the first postoperative period. We also found reappearance of heparin activity that was independent of the protamine dose in almost all our patients. We did not find any correlation between remaining or reappearing heparin activity and bleeding.   In conclusion, this thesis describes that moderate CPB times do not have the severe impairment on platelet function earlier described in the literature. The thesis also increases the knowledge regarding how protamine affects platelet function and how dosing of protamine does and does not affect the risk of remaining and reappearing heparin activity. Finally, we conclude that in most cases platelet function can be studied in venous and arterial blood interchangeably, but there might be some differences in platelet function depending on whether they are in the venous our arterial system. 

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Keyword

Cardiopulmonary bypass

Protamine

Platelet function

Coagulation

Publication and Content Type

vet (subject category)

dok (subject category)