Biological clocks and blood clots in space: circadian disruption-induced modulation of thrombosis risk.

内容摘要

Long-duration space missions expose astronauts to microgravity, radiation, confinement, fluid redistribution, and circadian disruption, which together induce physiological adaptations, including cardiovascular hemodynamics. Emerging evidence suggests that spaceflight may modulate hemostasis and potentially increase thrombotic risk in the head/neck; however, the association of circadian disruption and hemostasis in space, and its ground-based analogs, has yet to be systematically evaluated. This systematic review aimed to synthesize evidence from real-spaceflight missions and ground-based analogs to (i) characterize thrombosis-related and hemostatic adaptations, (ii) evaluate circadian remodeling under altered gravitational conditions, and (iii) identify mechanistic and methodological gaps linking biological timing to coagulation regulation in space. A systematic search of PubMed, Scopus, and Web of Science was conducted from January 2016 to January 2026. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies investigating circadian rhythms, clock-gene regulation, autonomic chronobiology, hemostasis, thrombosis, platelet biology, and coagulation pathways, in spaceflight or spaceflight analogs were systematically screened and analyzed. Thirty-eight studies met inclusion criteria, of which 20 (52.6%) primarily examined hemostasis and thrombosis outcomes and 18 (47.4%) focused on circadian regulation. Thrombosis-related investigations demonstrated dynamic modulation of coagulation cascades, platelet activation pathways, fibrinogen levels, endothelial markers, and complement components across dry immersion, head-down bed rest, animal unloading models, radiation exposure, hypergravity, and real astronaut missions. However, most hemostatic studies relied on end point or milestone-based sampling without circadian-phase resolution. In contrast, circadian-focused studies used dense temporal sampling and revealed phase shifts, altered autonomic rhythmicity, and disruption of molecular clock regulators under simulated and real space conditions, yet rarely assessed direct thrombotic end points. Importantly, no included study simultaneously assessed circadian-phase regulation and hemostatic outcomes, highlighting a critical lack of mechanistic evidence linking biological timing to thrombotic regulation in spaceflight environments. The absence of circadian phase-resolved hemostatic assessment represents a fundamental mechanistic gap. Future integrative chronothrombotic study designs are required to determine whether disrupted biological timing directly contributes to thrombotic vulnerability during spaceflight.