Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release.

The hemostatic alterations underlying the occasional bleeding diathesis associated with cardiopulmonary bypass surgery have been defined in 31 selected patients by simultaneously measuring the serial changes in concentration. function and kinetics of platelets. coagulation factors. and fibrinolytic components. The effects of uncomplicated bypass surgery were evaluated in 21 elective patients. Immediately upon bypass. the circulating levels of platelets. coagulation factors. and plasminogen regularly fell about 50% due to dilution with nonblood prime in the oxygenator apparatus. However. none of these components was reduced below established hemostatic levels at any time during or following the procedure. Furthermore. the functional transformation of fibrinogen to fibrin was not measurably impaired. Heparin effectively blocked both fibrinolysis and fibrinogen consumption during bypass and was consistently neutralized with protamine without rebound at the end of bypass. Circulating platelets were uniformly activated in elective patients during bypass through a process that involved release and partial depletion of a-granules. but not release of dense granule constituents. Platelet activation was associated with transient marked impairment of function as evidenced by striking prolongation of the bleeding time and defective aggregation in vitro. In uncomplicated patients. platelet function largely normalized within 1 hr after bypass. Controlled studies in baboons demonstrated that platelet dysfunction was produced by either cardiopulmonary bypass under normothermic conditions or by hypothermia alone without bypass. In the baboon model. defective platelet function was also transient and characterized by selective depletion of platelet a-granule contents without release of dense granule contents. By contrast. in all of 1 0 patients in whom bypass surgery was complicated by substantial abnormal bleeding. there was persistent bleeding time prolongation to greater than 25 mm that persisted for hours after bypass despite platelet counts above 1 OO.OOO/ sI. With platelet transfusions. the bleeding time shortened rapidly. followed by cessation of bleeding. From these studies we conclude that cardiopulmonary bypass patients demonstrate abnormal clinical bleeding when there is a persistence of platelet dysfunction manifested as a bleeding time of greater than 20 mm after protamine administration. Such bleeding patients with a prolonged bleeding time should receive platelet transfusions even when the platelet count is greater than 1 0O.000/zl.