Scientists Uncover Reason Why Hibernating Bears are Immune to Blood Clots

People who fly on long-haul flights and remain seated for extended periods can be at risk of developing dangerous blood clots, while hibernating bears are not. A new study, published in the journal Science on April 14, reveals that bears that sleep for the winter have low levels of a key protein needed to form blood clots. Platelets that lack this protein do not stick together easily, protecting bears from the development of potentially fatal blood clots. Mice and pigs with largely sedentary lifestyles also have low levels of the protein, as do humans with long-term mobility issues. Knowledge of how animals have adapted to protect themselves against immobility-related blood clots could help researchers develop drugs to mimic nature's solutions.

The protein, heat shock protein 47 (HSP47) is generally found in the cells that make up connective tissues, bone, and cartilage. HSP47 is also present in platelets, where it connects with collagen, aiding the sticking together of platelets, which aids in the response to cuts or other injuries but can lead to clots that block blood flow to the lungs. Drugs based on the study's findings would be designed to prevent HSP47 from interacting with proteins or immune cells that cause clotting.

Remaining still for extended periods, such as during air travel, raises the risk of developing deep vein thrombosis, rare but potentially dangerous blood clots that typically originate in the legs. Inflammation and slow blood flow during such periods can make clots more likely to form. Hibernating bears face similar immobility yet studies have indicated that they do not die of clot-linked conditions during hibernation. It has also been noted that people who experience long-term immobility, such as those with spinal cord injuries, do not develop clots more often than people with typical mobility.

In the study, blood samples from 13 wild brown bears (Ursus arctos) were analyzed in winter and summer. Platelets from blood samples taken during hibernation were less likely to clump together than summer samples, and ones that did clot did so more slowly. Researchers established that HSP47 in platelets was the reason why the bears did not clot. In hibernating bears, levels of the protein were drastically reduced compared with active animals.

Mice lacking HSP47 had fewer clots and lower levels of inflammation, and pigs that had recently given birth, making them largely immobile while nursing their young, also had lower levels of HSP47 compared with active pigs. The findings also extended to humans, with 12 otherwise healthy people who took part in a voluntary bed rest study spending a month immobile and having reduced levels of HSP47.

Marjory Brooks, a veterinarian and comparative hematologist at Cornell University, who was not involved in the study, commented that most animals use similar cells and proteins to create clots and prevent blood loss, but that variations might exist among specific species concerning what happens before a clot forms.

The knowledge of how human bodies control HSP47 is essential to ensure that potential drugs balance preventing clotting with avoiding excessive bleeding. The next step is to understand why the body creates less HSP47 in situations of immobility.