A Systematic Evaluation of the Effect of Temperature on Coagulation Enzyme Activity and Platelet Function

Abstract

Hypothermia is associated with an increased risk of bleeding and is a significant contributing factor to the morbidity and mortality of trauma and complicated surgical procedures. A core temperature of 33°C is associated with a significantly increased risk of death after trauma compared with 37°C. Hypothermia-associated bleeding has been hypothesized to result from dysregulation of enzymatic function, reduced platelet activity, and/or altered fibrinolysis. We systematically evaluated the effects of temperature on isolated pro- and anticoagulant enzyme processes and platelet activation and adhesion. We also evaluated the effects of temperature on complete coagulation systems (activated partial thromboplastin time and an in vitro, cell-based model of coagulation). Enzyme activities were only slightly reduced at 33°C versus 37°C, and this reduction was not statistically significant (p > 0.05). Platelet activation was also not significantly reduced at 33°C versus 37°C. Conversely, platelet aggregation and adhesion were significantly reduced at 33°C compared with 37°C (p < 0.05). Below 33°C, however, both enzyme activity and platelet function were significantly reduced. Our results suggest that bleeding observed at mildly reduced temperatures (33°–37°C) results primarily from a platelet adhesion defect, and not reduced enzyme activity or platelet activation. However, at temperatures below 33°C, both reduced platelet function and enzyme activity likely contribute to the coagulopathy.