Thromboxane Synthesis and Platelet Protein Release During Simulated Extracorporeal Circulation

Abstract

Platelet secretion induced by certain soluble aggregating agents is associated with thromboxane formation. Activation of platelets by artificial surfaces may involve similar biochemical pathways. Therefore, we monitored platelet release and formation of thromboxane B2. the stable end-product of thromboxane A2, during simulated extracorporeal circulation where contact between blood and synthetic surfaces is extensive. Fresh heparinized human blood was recirculated for 2 hr at 37°C at 1 liter/min in circuits (0.95 sqm) constructed of standard silicone rubber components (0.1 sqm) and a spiral coil membrane oxygenator (0.85 sqm). Within 2 min of recirculation, plasma levels of the platelet-specific protein, low-affinity platelet factor 4 (LA-PF4) rose from <1.5% to 11 % ±3% SEM of that which was released by triton X-100, indicating significant release of platelet α-granule contents. This occurred despite the absence of detectable thromboxane B2 in plasma (<0.5 pmole/ml). Between 2 and 15 min, plasma levels of LA-PF4 increased from 11% to 42% ± 3%, and plasma thromboxane B2 concentrations rose to 3.2 pmole/ml. Subsequently, thromboxane B2 levels continued to rise to 9.8 pmole/ml by 2 hr. Thromboxane B2 was not detected in blood from donors who had ingested aspirin, and the extent of platelet secretion was reduced by about 50% (25% at 2 hr). Thus, although a component of platelet granule release during extracorporeal recirculation appears to be associated with thromboxane synthesis, considerable release of LA-PF4 may occur by thromboxanβ-indβpen-dent pathways.