Space-related anemia is a hemolytic condition, according to study results published in Nature Medicine. The pattern of hemolysis in the three phases of the study (on Earth, in space, and back on Earth) confirmed that increased hemolysis was tightly linked to the space environment and suggests that the longer the exposure to space, the worse the anemia. Increased hemolysis as a primary effect of exposure to space constitutes a paradigm shift in the understanding of space anemia, according to the study authors.
“Space anemia had been measured in astronauts for over five decades with little data on its mechanism and, despite the many countermeasures of modern space travel (exercise, medical protocols, diet), space anemia is still present today,” said lead author, Guy Trudel, MD, of the Ottawa Hospital Research Institute in Ontario, Canada. “As we are planning longer missions of one year or more, this appeared like a significant knowledge gap.”
The advent of space tourism and commercialization also underscores the imperative to better understand space-induced anemia.
Previously documented space-induced anemia is characterized by a 10 to 12% decrease in red blood cell (RBC) mass occurring in the first 10 days in space, which is now understood to be an acute adaptation to major hemodynamic events of cephalad fluid shifts, hemoconcentration, and low erythropoietin (EPO) levels upon entering microgravity. Beyond 10 days in space, when the hemoglobin concentration returns to near-Earth values, it has been assumed that erythrocytic regulation proceeds as normal, but this has not been measured precisely. Recently, astronauts have been found to remain mildly hemoconcentrated throughout long-duration missions, with data showing that the severity, recovery time, and longitudinal effects of postflight anemia are proportional to the time spent in space.
For the present study, 14 astronauts were interviewed between 2015 and 2020, approximately one year ahead of their missions to the International Space Station (ISS). Participating astronauts collected air and blood samples three months before takeoff, four times onboard the ISS, and serially after landing. Preflight measures served as the comparator to test the effects of space exposure and determine whether one or more astronauts unknowingly had a beta-globin variant.
The primary outcome was elimination of carbon monoxide (CO) through pulmonary ventilation. Secondary outcomes included other direct (iron) and indirect markers of heme degradation (bilirubin, transferrin percent saturation, and ferritin), as well as haptoglobin, EPO, complete blood counts (CBCs), and C-reactive protein.
Findings provide “the first direct demonstration of upregulated hemolysis in space and support the hypothesis that space-related anemia is a hemolytic condition,” according to study authors. Results showed an association between space flight and persistently increased levels of products of hemoglobin degradation, carbon monoxide in alveolar air, and iron in serum. Mean baseline CO elimination was 1,662 ppb (95% CI 1,433-1,891) compared to 2,627 ppb (95% CI 2,342-2,913) after an average of 5 ± 1 days on the ISS, representing a 56% mean increase from preflight (95% CI 36-76). Serum iron, transferrin, and ferritin also increased.
Persistently increased CO elimination in space showed that hemolysis was not an acute adaptation to hemodynamic alterations upon entering microgravity. Rather, increased hemolysis constituted a primary effect of exposure to space, a finding that is strengthened by the postflight data, according to study authors.
One year after landing, the erythrocytic effects on the participating astronauts persisted, including increased levels of hemolysis, reticulocytosis, and hemoglobin.
The return to Earth’s gravity also caused major hemodynamic changes, as fluid shift reversal increased plasma volume and diluted RBCs. The astronaut cohort had an 8.8% (95% CI 8.1-9.5) decrease in hemoglobin concentration four days after landing compared to preflight, with five of 13 astronauts (38.5%) reaching clinical levels of anemia. The specific exercise and nutritional countermeasures of modern space travel did not prevent hemolysis and postflight anemia in the cohort, which could have health consequences, the authors noted.
These findings identify a mechanism for space-induced anemia and provide direction for future research to uncover the mechanism of hemolysis. This will allow for implementation of specific preventive or therapeutic countermeasures. In addition, “many of the changes seen in astronauts are similar to people on Earth who are inactive, such as patients in the intensive care unit, geriatric populations, and patients with disability, who have unexplained anemia,” Dr. Trudel said. “Our results suggest exploring the contribution of increased hemolysis to the anemia in these patient populations.”
The study’s recruitment of subjects was limited to astronauts; additional limitations included the potential confounding factors associated with exposure to space.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Trudel G, Shahin N, Ramsay T, Laneuville O, Louati H. Hemolysis contributes to anemia during long-duration space flight. Nat Med. 2022;28(1):59-62.
