Rising temperatures associated with climate change have significantly increased the risk of
heatstroke. Unfortunately, the trend is anticipated to persist and increasingly threaten vulnerable populations, particularly older adults. According to Japan's environment ministry, over 1000 people died from
heatstroke in 2021, and 86% of deaths occurred in those above 65. Since the precise mechanism of
heatstroke is not fully understood, we examined the pathophysiology by focusing on the microcirculatory derangement. Online search of published medical literature through MEDLINE and Web of Science using the term "
heatstroke," "heat-related illness," "
inflammation," "
thrombosis," "coagulation," "fibrinolysis," "endothelial cell," and "circulation." Articles were chosen for inclusion based on their relevance to
heatstroke,
inflammation, and
thrombosis. Reference lists were reviewed to identify additional relevant articles. Other than preexisting conditions (genetic background, age, etc.), factors such as hydration status, acclimatization, dysregulated coagulation, and
inflammation are the additional major factors that promote tissue malcirculation in
heatstroke. The fundamental pathophysiologic mechanisms significantly overlap with those seen in the systemic inflammatory response to
sepsis, and as a result, coagulation-predominant coagulopathy develops during heat stress. Although a
bleeding tendency is not common,
bleeding frequently occurs in the microcirculation, causing additional injury. Sterile
inflammation is mediated by proinflammatory
cytokines,
chemokines, and other humoral mediators in concert with cellular factors, including monocytes, neutrophils, platelets, and endothelial cells. Excess
inflammation results in inflammatory cell death, including pyroptosis and necroptosis, and the release of danger signals that further propagate systemic
inflammation and coagulopathy. Consequently,
thromboinflammation is the critical factor that induces microcirculatory disturbance in
heatstroke.