Hypothermia-induced activation of the splenic platelet pool as a risk factor for thrombotic disease in a mouse model. （マウス低体温症モデルにおける脾臓内血小板活性化は血栓症の危険因子となる）
著者
堀岡, 希衣
(Horioka, Kie)
上位タイトル
Journal of thrombosis and haemostasis
Vol.17,
No.10
(2019.
10)
,p.1762-
1771
識別番号
ISSN
1538-7933
DOI
10.1111/jth.14555
その他
PMID: 31237986
博士論文情報
学位授与番号
10107A547
学位授与年月日
2020-03-25
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
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 CD62P-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 (PF4) 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 PF4 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.
