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The Effects of Hyperthermia On Platelet Physiology.

Quanwei Shi, Zhicheng Wang, Rong Yan, Juan Du, Jun Liu, Changgeng Ruan and Kesheng Dai

Abstract

Abstract 2422

Poster Board II-399

Introduction: In some patients with fever or hyperthermia, hemorrhage is a significant pathological feature, which incurs severe or even fatal consequence. Although the mechanisms of hemorrhage in patients with hyperthermia or fever have been though to be complex, whether there is an association between hemorrhage and hyperthermia or fever is not well understood. Platelets play a central role in maintaining integrity of endothelium and biological hemostasis. Platelet count obviously reduces in most of patients with dengue fever or heatstroke, and reduced platelet aggregations have been found in patients with hemorrhage fever, raising the possibility that fever or hyperthermia incurs reduction of platelet count or function leading to hemorrhage.

Methods and Results: To explore the effect of hyperthermia on platelet function, platelet-rich plasma (PRP) was isolated and incubated at hypothermia (22 degrees C), normothermia (37 degrees C) or hyperthermia (40 and 42 degrees C) for 1 or 2 hours, and then induced to aggregation by ADP. Platelet aggregation was significantly reduced with the growth of temperature in a time-dependent manner. To exclude the possible interference from plasma proteins, and to further investigate the effects of hyperthermia on platelet function, alpha-thrombin induced platelet aggregations were examined in washed platelets incubated at different temperatures for 1 or 2 hours. Washed platelets presented normal aggregation response to alpha-thrombin in platelets incubated at hypothermia, whereas alpha-thrombin induced platelet aggregations reduced gradually with the increase of temperature and time duration. Next, we investigated whether the reductions of platelet aggregation were resulted from platelet apoptosis under high temperature conditions. Hyperthermia gradually induced apoptotic events in platelets with the increase of temperature and time duration, including depolarization of mitochondrial inner transmembrane potential (ΔΨm), gelsolin cleavage, and phosphatidylserine (PS) exposure. Furthermore, hyperthermia incurs platelet glycoprotein (GP) Ibalpha ectodomain shedding.

Conclusions: These results indicate that hyperthermia induces platelet apoptosis, thus suggesting the possible reason why platelet count or function was reduced in some patients with fever or hyperthermia. These findings not only have important implications for the pathogenesis of hemorrhage in some fever or hyperthermia-related diseases, but also suggest that attentions should be paid on platelet apoptosis under relative high temperature conditions, such as during hyperthermia therapy or platelet storage.

Disclosures: No relevant conflicts of interest to declare.