Soluble thrombomodulin ameliorates aberrant hemostasis after rewarming in a rat accidental hypothermia model

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. •Platelets and coagulation activation occur after rewarming of hypothermia.•Such activation leads to thrombosis formation in the renal glomeruli.•rTM administration inhibits thrombus formation in the renal glomeruli.•rTM exerts its anticoagulant effect by degrading and inactivating coagulation factors.•rTM may provide appropriate coagulant management after rewarming of hypothermia.