Spaceflight-Associated Anemia and Hemolysis: A Systematic Review of Hematological Adaptations to Microgravity

Introduction: Spaceflight-associated anemia is an emerging concern for long-duration missions, yet its biological mechanisms remain incompletely defined. Early observations attributed post-flight reductions in red blood cell mass mainly to plasma volume shifts and suppressed erythropoiesis, whereas recent evidence suggests that sustained hemolysis may play a central role. This systematic review aimed to synthesize human and translational evidence on anemia, hemolysis, erythropoiesis, and iron metabolism during spaceflight and microgravity-related conditions.

Methods: A PRISMA 2020-guided systematic review was conducted using PubMed/MEDLINE, PubMed Central, NASA Technical Reports Server, ScienceDirect, Springer Nature, JAMA Network, and manual reference screening. Search terms combined spaceflight, microgravity, astronauts, anemia, hemolysis, erythropoiesis, red blood cells, hemoglobin, erythropoietin, ferritin, and iron metabolism. Eligible studies included human spaceflight investigations or directly relevant microgravity-related studies reporting hematological outcomes. Narrative reviews, commentaries, animal-only studies, and reports without hematological endpoints were excluded.

Results: Forty-nine records were identified, 18 duplicates were removed, and 31 records were screened. Fourteen full texts were assessed for eligibility, and 13 studies were included in the qualitative synthesis. Evidence from Gemini, Spacelab, Shuttle, and International Space Station missions consistently indicated reductions in red blood cell mass, altered erythropoietin response, changes in iron availability, and post-flight anemia. Recent long-duration mission data showed increased hemoglobin degradation products, supporting hemolysis as a major contributor to spaceflight-associated anemia.

Conclusions: Spaceflight-associated anemia appears to result from interacting mechanisms involving hemolysis, altered erythropoiesis, plasma volume adaptation, and iron redistribution. Standardized longitudinal hematological monitoring is essential for future lunar and Mars missions.