Hibernation and hemostasis

Abstract

Hibernating mammals have developed many physiological adaptations to accommodate their decreased metabolism, body temperature, heart rate and prolonged immobility without suffering organ injury. During hibernation, the animals must suppress blood clotting to survive prolonged periods of immobility and decreased blood flow that could otherwise lead to the formation of potentially lethal clots. Conversely, upon arousal hibernators must be able to quickly restore normal clotting activity to avoid bleeding. Studies in multiple species of hibernating mammals have shown reversible decreases in circulating platelets, cells involved in hemostasis, as well as in protein coagulation factors during torpor. Hibernator platelets themselves also have adaptations that allow them to survive in the cold, while those from non-hibernating mammals undergo lesions during cold exposure that lead to their rapid clearance from circulation when re-transfused. While platelets lack a nucleus with DNA, they contain RNA and other organelles including mitochondria, in which metabolic adaptations may play a role in hibernator’s platelet resistance to cold induced lesions. Finally, the breakdown of clots, fibrinolysis, is accelerated during torpor. Collectively, these reversible physiological and metabolic adaptations allow hibernating mammals to survive low blood flow, low body temperature, and immobility without the formation of clots during torpor, yet have normal hemostasis when not hibernating. In this review we summarize blood clotting changes and the underlying mechanisms in multiple species of hibernating mammals. We also discuss possible medical applications to improve cold preservation of platelets and antithrombotic therapy.

Mesocricetus auratus (Golden Syrian Hamster) Experimental Model of SARS-CoV-2 Infection Reveals That Lung Injury Is Associated with Phenotypic Differences Between SARS-CoV-2 Variants

“…We highlight that microthrombosis, NETs, and myeloperoxidase-positive cells were absent in our study; on the other hand, in COVID-19 patients, activated platelets can release vasoactive, haemostatic, and inflammatory mediators, triggering the coagulation cascade, providing a procoagulant surface for secondary haemostasis and, additionally, inducing the release of neutrophil extracellular traps [ 58 ]. The resistance to pulmonary microthrombosis observed may be explained by the species-specific mechanism of clot breakdown observed in hamsters during cold-stress hibernation [ 59 ]. In our hypothesis, this efficient mechanism of clot breakdown should be studied further until it is well understood since it could be a method of coagulopathy prevention in COVID-19 patients.…”

Mesocricetus auratus (Golden Syrian Hamster) Experimental Model of SARS-CoV-2 Infection Reveals That Lung Injury Is Associated with Phenotypic Differences Between SARS-CoV-2 Variants

“…We highlight that microthrombosis, NETs, and myeloperoxidase-positive cells were absent in our study; on the other hand, in COVID-19 patients, activated platelets can release vasoactive, haemostatic, and inflammatory mediators, triggering the coagulation cascade, providing a procoagulant surface for secondary haemostasis and, additionally, inducing the release of neutrophil extracellular traps [ 58 ]. The resistance to pulmonary microthrombosis observed may be explained by the species-specific mechanism of clot breakdown observed in hamsters during cold-stress hibernation [ 59 ]. In our hypothesis, this efficient mechanism of clot breakdown should be studied further until it is well understood since it could be a method of coagulopathy prevention in COVID-19 patients.…”

Hibernating or not hibernating? Brown bears’ response to a mismatch between environmental natural cues and captive management, and its welfare implications

“…Wild bear hibernation response has proved to retain a certain degree of flexibility [ 4 , 12 , 18 , 47 – 49 ] in response to extremely variable environmental conditions experienced in different parts of their wide geographical distribution (ranging from 20°N to the Arctic Ocean [ 81 ]). Brown bear, in fact, has been defined as a shallow hibernator species [ 24 , 82 , 83 ] as opposed to obligate hibernators (e.g., chipmunks, ground squirrel and groundhog [ 24 , 84 ]). In the latter, for example, body temperature reaches values close to freezing, in comparison to the about 31–32°C reported for bears [ 4 ], although mechanisms employed by small and large heterotherms, functional to metabolic rate reduction, are likely to be different due to different surface-to-volume ratios and related energetic challenges [ 4 , 85 ].…”

Sleep and Dreams as Reflected by Science Fiction Literature and Films—Anything to Learn From?

“… 2024 ; Vrij et al. 2023 ). Of note, cryonics (the process of preserving life, or ‘pausing death’, through subfreezing) is something that is commercially available today.…”

“…These natural processes are under investigation to explore whether human biology can be modified to mimic these states for long-term space travel. Researchers have induced hypothermia in medical settings to slow metabolism during surgery, hinting that similar methods might one day be used to induce hibernation for astronauts (for a general overview see, e.g., Ohba and Yamaguchi 2025;Liu et al 2024;Vrij et al 2023). Of note, cryonics (the process of preserving life, or 'pausing death', through subfreezing) is something that is commercially available today.…”

Mesocricetus auratus (Golden Syrian Hamster) Experimental Model of SARS-CoV-2 Infection Reveals That Lung Injury Is Associated with Phenotypic Differences Between SARS-CoV-2 Variants

“…We highlight that microthrombosis, NETs, and myeloperoxidase-positive cells were absent in our study; on the other hand, in COVID-19 patients, activated platelets can release vasoactive, haemostatic, and inflammatory mediators, triggering the coagulation cascade, providing a procoagulant surface for secondary haemostasis and, additionally, inducing the release of neutrophil extracellular traps [ 58 ]. The resistance to pulmonary microthrombosis observed may be explained by the species-specific mechanism of clot breakdown observed in hamsters during cold-stress hibernation [ 59 ]. In our hypothesis, this efficient mechanism of clot breakdown should be studied further until it is well understood since it could be a method of coagulopathy prevention in COVID-19 patients.…”

Hibernating or not hibernating? Brown bears’ response to a mismatch between environmental natural cues and captive management, and its welfare implications

“…Wild bear hibernation response has proved to retain a certain degree of flexibility [ 4 , 12 , 18 , 47 – 49 ] in response to extremely variable environmental conditions experienced in different parts of their wide geographical distribution (ranging from 20°N to the Arctic Ocean [ 81 ]). Brown bear, in fact, has been defined as a shallow hibernator species [ 24 , 82 , 83 ] as opposed to obligate hibernators (e.g., chipmunks, ground squirrel and groundhog [ 24 , 84 ]). In the latter, for example, body temperature reaches values close to freezing, in comparison to the about 31–32°C reported for bears [ 4 ], although mechanisms employed by small and large heterotherms, functional to metabolic rate reduction, are likely to be different due to different surface-to-volume ratios and related energetic challenges [ 4 , 85 ].…”

Sleep and Dreams as Reflected by Science Fiction Literature and Films—Anything to Learn From?

“… 2024 ; Vrij et al. 2023 ). Of note, cryonics (the process of preserving life, or ‘pausing death’, through subfreezing) is something that is commercially available today.…”

“…These natural processes are under investigation to explore whether human biology can be modified to mimic these states for long-term space travel. Researchers have induced hypothermia in medical settings to slow metabolism during surgery, hinting that similar methods might one day be used to induce hibernation for astronauts (for a general overview see, e.g., Ohba and Yamaguchi 2025;Liu et al 2024;Vrij et al 2023). Of note, cryonics (the process of preserving life, or 'pausing death', through subfreezing) is something that is commercially available today.…”

Mesocricetus auratus (Golden Syrian Hamster) Experimental Model of SARS-CoV-2 Infection Reveals That Lung Injury Is Associated with Phenotypic Differences Between SARS-CoV-2 Variants

“…We highlight that microthrombosis, NETs, and myeloperoxidase-positive cells were absent in our study; on the other hand, in COVID-19 patients, activated platelets can release vasoactive, haemostatic, and inflammatory mediators, triggering the coagulation cascade, providing a procoagulant surface for secondary haemostasis and, additionally, inducing the release of neutrophil extracellular traps [ 58 ]. The resistance to pulmonary microthrombosis observed may be explained by the species-specific mechanism of clot breakdown observed in hamsters during cold-stress hibernation [ 59 ]. In our hypothesis, this efficient mechanism of clot breakdown should be studied further until it is well understood since it could be a method of coagulopathy prevention in COVID-19 patients.…”

Hibernating or not hibernating? Brown bears’ response to a mismatch between environmental natural cues and captive management, and its welfare implications

“…Wild bear hibernation response has proved to retain a certain degree of flexibility [ 4 , 12 , 18 , 47 – 49 ] in response to extremely variable environmental conditions experienced in different parts of their wide geographical distribution (ranging from 20°N to the Arctic Ocean [ 81 ]). Brown bear, in fact, has been defined as a shallow hibernator species [ 24 , 82 , 83 ] as opposed to obligate hibernators (e.g., chipmunks, ground squirrel and groundhog [ 24 , 84 ]). In the latter, for example, body temperature reaches values close to freezing, in comparison to the about 31–32°C reported for bears [ 4 ], although mechanisms employed by small and large heterotherms, functional to metabolic rate reduction, are likely to be different due to different surface-to-volume ratios and related energetic challenges [ 4 , 85 ].…”

Sleep and Dreams as Reflected by Science Fiction Literature and Films—Anything to Learn From?

“… 2024 ; Vrij et al. 2023 ). Of note, cryonics (the process of preserving life, or ‘pausing death’, through subfreezing) is something that is commercially available today.…”

“…These natural processes are under investigation to explore whether human biology can be modified to mimic these states for long-term space travel. Researchers have induced hypothermia in medical settings to slow metabolism during surgery, hinting that similar methods might one day be used to induce hibernation for astronauts (for a general overview see, e.g., Ohba and Yamaguchi 2025;Liu et al 2024;Vrij et al 2023). Of note, cryonics (the process of preserving life, or 'pausing death', through subfreezing) is something that is commercially available today.…”