Anticoagulants for the prevention and treatment of venous thromboembolism in humans exposed to microgravity: A hybrid systematic and narrative review.

Importance: Microgravity induces physiological changes that may predispose astronauts to venous thromboembolism (VTE), yet no studies have directly evaluated the safety or efficacy of anticoagulation in this environment. Objective: To perform a systematic review of anticoagulant use for VTE prevention and treatment in microgravity-exposed individuals and, in the absence of eligible studies, to synthesize existing physiologic and terrestrial evidence relevant to VTE risk and thromboprophylaxis. Methods: A comprehensive search of 13 biomedical and aerospace databases (MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, CINAHL, NASA Technical Reports Server, ESA archives, ClinicalTrials.gov, NASA Life Sciences Data Archive, ISS Publications Archive, DLR database, NASA SS Research Database) was performed following PRISMA guidelines. Eligible studies included astronauts or individuals in microgravity analogs receiving pharmacologic anticoagulation for VTE prevention or treatment. Results: The search yielded zero studies meeting predefined PICOS criteria. To contextualize this absence of evidence, we synthesized key physiologic findings from microgravity and ground-based analog studies demonstrating venous stasis, endothelial dysfunction, increased fibrinogen synthesis, altered platelet function, and hypercoagulability. Conclusions and relevance: VTE appears rare in spaceflight, but the absence of direct evidence on anticoagulation underscores a critical research gap. Further studies are needed to evaluate anticoagulant safety and efficacy in microgravity, adapt risk assessment tools, and develop evidence-based protocols to safeguard astronaut health.