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 α-granule proteins into plasma (platelet factor 4 and β-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, plateletdense 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 < 0.01 compared with untreated control values) but did not block the release of α-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 α 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.