Prevention of acquired transient defect in platelet plug formation by infused prostacyclin.

Cardiopulmonary bypass in baboons produced transient severe platelet dysfunction (bleeding times prolonged to 27.8 +/- 1.4 min compared with 3.9 +/- 0.7 baseline) that was associated with a parallel release of platelet alpha-granule proteins into plasma (platelet factor 4 and beta-thromboglobulin levels of 28.8 +/- 9.3 and 20.0 +/- 1.8 ng/ml, respectively) and their clearance into urine with a reciprocal depletion from circulating platelets. In contrast, platelet-dense granules did not undergo significant release. The bleeding times normalized rapidly following bypass (8.5 +/- 1.4 min at 1 hr). The infusion of prostacyclin (PGI2) into the bubble oxygenator during bypass (40--80 ng/kg/min) prevented the prolongation in bleeding time (p less than 0.01 compared with untreated control values) but did not block the release of alpha-granule proteins. Dosages outside this range were associated with prolonged bleeding times. These results show that transient platelet dysfunction occurring during cardiopulmonary bypass represents activation of platelets independent of alpha or dense granule release and is blocked by potent short-acting inhibition of platelet function using PGI2 infused into the oxygenator apparatus at optimal therapeutic doses.