Department of Emergency Medicine, Asahikawa Medical University Hospital, Japan.
Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Japan.
Biochem Biophys Res Commun. 2022 Jan 8;587:1-8. doi: 10.1016/j.bbrc.2021.11.086. Epub 2021 Nov 26.
Accidental hypothermia (AH) sometimes leads to coagulation disorder, especially in severe AH. We previously demonstrated that intrasplenic platelet activation caused aberrant hemostasis and thrombus formation after rewarming in a murine AH model. However, no study has focused on the appropriate management of platelets causing coagulation activation after rewarming of AH. We investigated whether or not recombinant soluble thrombomodulin (rTM) can suppress thrombosis formation after rewarming using a rat AH model.
Wistar rats were exposed to an ambient temperature of -20 °C under general anesthesia until their rectal temperature decreased to 26 °C. The Hypo group rats (n = 5) were immediately euthanized, while the Hypo/Re group (n = 5) and rTM group rats (n = 5), which were administered rTM (1 mg/kg) via the tail vein, were rewarmed until the rectal temperature returned to 34 °C and then euthanized 6 h later. Tissue and blood samples were collected from all rats for histopathological and coagulation analyses at euthanasia.
There was no significant change in the D-dimer level in the Hypo group rats, while the D-dimer level was significantly elevated at 6 h after rewarming in the Hypo/Re group rats (P = 0.015), and histopathology detected both fibrin and platelets in the renal glomerulus. However, the rTM group rats did not show any elevation of the D-dimer levels at 6 h after rewarming, and no fibrin was noted on histopathology.
rTM may be useful as an appropriate anticoagulant in cases of aberrant hemostasis after rewarming of AH.
意外低体温(AH)有时会导致凝血功能障碍,尤其是在严重的 AH 中。我们之前的研究表明,在鼠 AH 模型中,脾内血小板活化导致复温后异常止血和血栓形成。然而,目前尚无研究关注 AH 复温后导致凝血激活的血小板的适当处理。我们使用大鼠 AH 模型研究了重组可溶性血栓调节蛋白(rTM)是否可以抑制复温后血栓形成。
在全身麻醉下,将 Wistar 大鼠暴露于环境温度为-20°C,直至直肠温度降至 26°C。Hypo 组大鼠(n=5)立即安乐死,而 Hypo/Re 组(n=5)和 rTM 组大鼠(n=5)则通过尾静脉给予 rTM(1mg/kg),并复温至直肠温度恢复至 34°C,然后 6 小时后安乐死。所有大鼠在安乐死时采集组织和血液样本,用于组织病理学和凝血分析。
Hypo 组大鼠的 D-二聚体水平没有明显变化,而 Hypo/Re 组大鼠复温 6 小时后 D-二聚体水平显著升高(P=0.015),组织病理学检查发现肾小球内既有纤维蛋白又有血小板。然而,rTM 组大鼠复温 6 小时后 D-二聚体水平没有升高,组织病理学也没有发现纤维蛋白。
rTM 可能是一种有用的抗凝剂,适用于 AH 复温后异常止血的情况。