Platelet levels and activity are decreased in hibernating 13‐lined ground squirrels which may prevent venous thromboembolism (879.17)

Abstract

The objective of this study is to determine how a hibernating mammal avoids the formation of blood clots under periods of low blood flow. Hibernating ground squirrels have dramatically decreased heart rates (3‐5 beats per minute) and blood flow, which should put them at risk of forming deep vein thrombi. In response, they have several adaptations during hibernation that prevent blood clotting, including 3‐fold decreases in Factors VIII and IX, and 10‐fold decreases in platelets. During hibernation, platelets are maintained at temperatures of 4‐8°C for up to six months. Within two hours of arousal, platelet levels return to normal, are not rapidly cleared from circulation, and are still functional. We have shown that in addition to decreased clotting factors, ground squirrels have a 10‐fold decrease in von Willebrand factor (vWF) protein and a 3‐fold decrease in vWF mRNA during hibernation. Platelets adhere to exposed collagen in a wound through binding to vWF, and unlike other mammalian platelets, cold storage of ground squirrel platelets does not increase binding of vWF. Ground squirrel platelets are also atypical in that their microtubules are cold‐resistant and change in shape from a circumferential ring to an equatorial rod once they reach 20ºC. This shape change was originally thought to trap the platelets in the spleen, but splenectomized and sham operated ground squirrels had the same platelet levels during torpor and interbout arousal, suggesting storage in an extrasplenic location. Finally, no evidence of irreversible cardiac ischemic damage was observed during hibernation through either histological staining or blood markers including troponin T, lactate dehydrogenase and creatine kinase. Taken together, these results suggest that ground squirrels avoid deep vein thrombosis by reversibly decreasing platelet levels and activity during hibernation.Grant Funding Source: Supported by NIH grant 2R15HL093680‐02