Isaac Ponder

Background: Disseminated intravascular coagulation (DIC) is an acquired syndrome of systemic coagulation activation that may cause thrombosis, bleeding, and organ failure. Diagnosis relies on an inciting condition with evolving abnormalities in platelet count, prothrombin time, fibrinogen, and fibrin-related markers, while treatment remains largely directed at the underlying trigger. ^1,2 For space exploration, radiation exposure is a mission-critical concern because crews traveling beyond low Earth orbit lose much of Earth’s magnetic shielding and may encounter high energy galactic cosmic radiation or solar particle events. ³ Severe radiation injury has been associated with radiation-induced coagulopathy (RIC), a spectrum of coagulation, inflammatory, endothelial, and hemorrhagic abnormalities that can resembled DIC clinically. ^4,5

Objective: This review evaluates whether mechanistic animal studies and human biomarker data support multimodal early detection of severe RIC before DIC-like systemic failure develops in spaceflight-relevant radiation exposure scenarios.

Search Methods: PubMed was searched for literature published from 2017 to 2023 using the keywords “disseminated intravascular coagulation,” “radiation-induced coagulopathy,” “space radiation,” “Göttingen minipig,” “thromboelastography,” and “D-dimer.” Five primary studies were selected to summarize RIC progression, potential biomarkers, high-risk phenotypes, countermeasures, and human translation.

Results: Thrall et al. developed a Göttingen minipig time-course model after total-body irradiation and showed that thromboelastography abnormalities clustered during days 10 to 15 post-irradiation. Additionally, they found that decedent animals showed differences in factors XII and XIII, protein C, and antiplasmin, with factor XII trending downward as early as day 4. ⁴ Hritzo et al. found that bleeding occurred in 61% of decedent minipigs but only 6% of survivors, and that thrombocytopenia alone was not a reliable measure of predicting hemorrhage. Instead, severe RIC reflect co-occurring anemia, neutropenia, inflammation, endothelial dysfunction, reduced nitric oxide bioavailability, and cardiovascular changes. Also, fibrin deposition was present in the decedent hearts and lungs, but the pattern did not support classic DIC. ⁵ Kenchegowda et al. further identified a high-risk phenotype in minipigs involving selective IGF-1 resistance, oxidative stress, decreased BH4 and nitric oxide, and impaired endothelial protective signaling despite similar thrombocytopenia. ⁶ Rittase et al. demonstrated that captopril improved survival and hematologic recovery while reducing inflammatory markers in irradiated Göttingen minipigs, suggesting that some radiation injury pathways may be modifiable. ⁷ Finally, Louneva et al. showed that D-dimer, a familiar clinical marker of fibrin turnover, was elevated in human radiotherapy cancer patients before, during and after treatment, supporting its role as a possible component as a radiation injury biomarker. ⁸

Conclusion: The reviewed literature supports RIC as an early, multifactorial syndrome that extends beyond platelet loss and may progress toward DIC-like clinical failure through inflammatory, endothelial, coagulation-factor, and vascular signaling pathways. Future space medicine research should validate practice biomarker panels that combine viscoelastic testing, coagulation factors, inflammatory and endothelial markers, and D-dimer to support earlier warning, crew monitoring, and countermeasure development during long-duration missions, especially before irreversible hemorrhagic dysfunction occurs.

Works Cited:

1. Levi M, Scully M. How I treat disseminated intravascular coagulation. Blood. 2018;131(8):845-854. doi:10.1182/blood-2017-10-804096
2. Popescu NI, Lupu C, Lupu F. Disseminated intravascular coagulation and its immune mechanisms. Blood. 2022;139(13):1973-1986. doi:10.1182/blood.2020007208
3. Chancellor JC, Blue RS, Cengel KA, et al. Limitations in predicting the space radiation health risk for exploration astronauts. NPJ Microgravity. 2018;4:8. doi:10.1038/s41526-018-0043-2
4. Thrall KD, Mahendra S, Jackson MK. A Göttingen minipig model of radiation-induced coagulopathy. Int J Radiat Biol. 2021;97(sup1):S63-S72. doi:10.1080/09553002.2020.1820600
5. Hritzo B, Legesse B, Ward JM, et al. Investigating the multifaceted nature of radiation-induced coagulopathies in a Göttingen minipig model of hematopoietic acute radiation syndrome. Radiat Res. 2021;196(2):156-174. doi:10.1667/RADE-20-00073.1
6. Kenchegowda D, Legesse B, Hritzo B, et al. Selective insulin-like growth factor resistance associated with heart hemorrhages and poor prognosis in a novel preclinical model of the hematopoietic acute radiation syndrome. Radiat Res. 2018;190(2):164-175. doi:10.1667/RR14993.1
7. Rittase WB, McCart EA, Muir JM, et al. Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome. PLoS One. 2021;16(8):e0256208. doi:10.1371/journal.pone.0256208
8. Louneva N, Maity A, Kennedy AR. Plasma D-dimer levels are elevated in radiation oncology patients. Radiat Res. 2020;193(1):46-53. doi:10.1667/RR15429.1