In vitro hypothermia enhances platelet GPIIb-IIIa activation and P-selectin expression.

BACKGROUND: A clinical bleeding diathesis is associated with hypothermia. Inhibition of platelet reactivity is the purported cause of this coagulopathy despite inconsistent evidence to support this hypothesis. To clarify the effect of temperature on intrinsic platelet function, platelet GPllb-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 activation was assessed by aggregometry and by cytometric analysis of platelet binding of fibrinogen, PAC-1, and P-selectin antibodies. Measurements 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 receptor activating peptide.
RESULTS: Agonist-induced platelet aggregation and fibrinogen binding were significantly greater at 22 degrees C and 33 degrees C than at 37 degrees C. Platelet fibrinogen binding values to 20 micro 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 aggregation responses of platelets that were cooled and rewarmed were indistinguishable from those of platelets maintained at 37 degrees C throughout the study. Platelet binding of PAC-1 and P-selectin antibodies was greater under hypothermic conditions.
CONCLUSIONS: Aggregation, fibrinogen binding, PAC-1 binding, and P-selectin antibody binding studies showed that platelet GPIIb-IIIa activation and alpha-granule release were enhanced at hypothermic temperatures. Thus hypothermia appears to increase the ability of platelets to respond to activating stimuli. The coagulopathy associated with hypothermia is not likely to be the result of an intrinsic defect in platelet function.