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Hypothermia‐induced activation of the splenic platelet pool as a risk factor for thrombotic disease in a mouse model
Author(s) -
Horioka Kie,
Tanaka Hiroki,
Isozaki Shotaro,
Okuda Katsuhiro,
Asari Masaru,
Shiono Hiroshi,
Ogawa Katsuhiro,
Shimizu Keiko
Publication year - 2019
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14555
Subject(s) - platelet , hypothermia , platelet factor 4 , platelet activation , medicine , von willebrand factor , spleen , hemostasis , endocrinology , immunology
Background Hypothermia, either therapeutically induced or accidental (ie, an involuntary decrease in core body temperature to <35°C), results in hemostatic disorders. However, it remains unclear whether hypothermia enhances or inhibits coagulation, especially in severe hypothermia. The present study evaluated the thrombocytic and hemostatic changes in hypothermic mice. Methods C57Bl/6 mice were placed at an ambient temperature of −20°C under general anesthesia. When the rectal temperature decreased to 15°C, 10 mice were immediately euthanized, while another 10 mice were rewarmed, kept in normal conditions for 24 hours, and then euthanized. These treatments were also performed in 20 splenectomized mice. Results The hypothermic mice had adhesion of CD 62P‐positive platelets with high expression of von Willebrand factor ( vWF ) in their spleens, while the status of the peripheral platelets was unchanged. Furthermore, the plasma levels of platelet factor 4 ( PF 4) and pro‐platelet basic protein ( PPBP ), which are biomarkers for platelet degranulation, were significantly higher in hypothermic mice than in control mice, indicating that hypothermia activated the platelets in the splenic pool. Thus, we analyzed these biomarkers in asplenic mice. There was no increase in either PF 4 or PPBP in splenectomized hypothermic mice. Additionally, the plasma D‐dimer elevation and microthrombosis were caused in rewarmed mice, but not in asplenic rewarmed mice. Conclusions Our results indicate that hypothermia leads to platelet activation in the spleen via the upregulation of vWF , and this activation causes hypercoagulability after rewarming.