IN-VITRO HYPOTHERMIA ENHANCES PLATELET GPIIB-IIIA ACTIVATION AND P-SELECTIN EXPRESSION

Background: A clinical bleeding diathesis is associated with hypotherm ia. Inhibition of platelet reactivity is the purported cause of this c oagulopathy despite inconsistent evidence to support this hypothesis. To clarify the effect of temperature on intrinsic platelet function, p latelet GPIIb-IIIa activation and P-selectin expression were assessed under normothermic and hypothermic conditions in vitro, Methods: Blood was obtained by venipuncture from healthy volunteers. Platelet activa tion was assessed by aggregometry and by cytometric analysis of platel et binding of fibrinogen, PAC-1, and P-selectin antibodies. Measuremen ts were made at normothermia (37 degrees C), moderate hypothermia (33 degrees C), and profound hypothermia (22 degrees C) after stimulating samples with adenosine diphosphate (ADP), collagen, or thrombin recept or activating peptide. Results: Agonist-induced platelet aggregation a nd fibrinogen binding were significantly greater at 22 degrees C and 3 3 degrees C than at 37 degrees C. Platelet fibrinogen binding values t o 20 mu M ADP were 23,400, 14,300, and 9,700 molecules/platelet at 22 degrees C, 33 degrees C, and 37 degrees C, respectively. The aggregati on responses of platelets that were cooled and rewarmed were indisting uishable from those of platelets maintained at 37 degrees C throughout the study. Platelet binding of PAC-I and P-selectin antibodies was gr eater under hypothermic conditions. Conclusions: Aggregation, fibrinog en binding, PAC-1 binding, and P-selectin antibody binding studies sho wed that platelet GPIIb-IIIa activation and cu-granule release were en hanced at hypothermic temperatures. Thus hypothermia appears to increa se the ability of platelets to respond to activating stimuli. The coag ulopathy associated with hypothermia is not likely to be the result of an intrinsic defect in platelet function.