VT - Attachment A - PWS.pdf

Attachment A – PWS Venus Thrombosis (VT) 9/24/2026

Venus Thrombosis (VT)

Performance Work Statement (PWS)

1. Description The National Aeronautics and Space Administration (NASA) Human Research Program (HRP) has a requirement for application of current, enhanced, or novel approaches to surveil, reduce risk of, and/or prevent venous thrombosis (VT) during spaceflight. This topic includes preflight medical screening, individual risk assessment, monitoring approaches, and countermeasures for spaceflight VT.

2. Scope of Work Work performed will focus on applied research and shall not include tissue chip/organoid pathophysiology development, Earth-independent decision-making support tools, emerging VT pharmaceutical treatments, or modeling (i.e., artificial intelligence, machine learning).

The Contractor shall provide all management, supervision, labor, personnel, materials, equipment, tools, supplies, facilities, and transportation necessary to perform all work required under this PWS.

3. Background A VT was identified in the internal jugular vein (IJV) of an astronaut during a research study of fluids shifts in weightlessness (a). This incidental finding was subsequently confirmed by a clinically guided ultrasound examination with 2-D imaging, color Doppler, and compression (b). While the crewmember was successfully treated with anti-coagulants on-orbit and regression of the thrombus was observed over the course of therapy, the absence of spontaneous flow persisted through 90 days of treatment. Anti-coagulation therapy was discontinued 4 days before landing, and the astronaut was safely returned to Earth without further complications. No thrombus was detected 10 days after landing, and the astronaut was asymptomatic during the subsequent 6 months. Additionally, in a retrospective evaluation of the images from the research study, a partially occlusive thrombus was suspected in a second crewmember but it was not confirmed using standard clinical practices (a).

Previously, Internal Jugular Vein (IJV) thrombosis was not a recognized concern for crew health during weightlessness, owing to its low terrestrial prevalence (c, d).

Following this event, medical surveillance for VT was initiated among U.S. Orbital Segment astronauts (e). Current medical assessments required for International Space Station (ISS) astronauts include assessment of genetic predisposition to thrombosis and preflight magnetic resonance imaging of the head and neck (TWIST sequence with gadolinium contrast), as well as bilateral duplex ultrasound of the extracranial IJVs with breathing and compression maneuvers performed before and during spaceflight. Given that the initial case was asymptomatic, there is a concern that there have been other cases that were overlooked or undetected given the relatively large proportion of astronauts in whom characteristics of impaired IJV flow or stasis has been observed (a, e). Several peer-reviewed publications have aimed to describe factors that might contribute to VT during spaceflight (f-q). The space agencies’ summaries of current state of knowledge and plans for future work are documented in NASA’s Office of the Chief Medicine Office Technical Brief, ESA’s Operations-Focused VT Strategic Roadmap, and ESA's Medical Operations priorities document (See Additional Resources section below). Recently NASA and ESA have partnered to initiate a comprehensive pre- and inflight study of cerebral venous outflow, anatomical variation, and biomarkers of hemostasis to be completed before retirement of the ISS.

Given that medical capabilities during exploration missions to the Moon and Mars may be limited, the identification of prophylactic countermeasures to mitigate the risk of VT and interventions that can be used to manage thrombosis cases are of great importance to crew health and mission success. Venous thrombosis has been observed in at least one astronaut participating in long-duration spaceflight to the ISS

(a) but other future research platforms might include commercial vehicles for orbital and suborbital spaceflight with more limited medical hardware capabilities. To date, there have been no reports of VT or IJV flow impairments/stasis in strict head-down tilt bed rest (r), but stasis has been observed in a small number of study participants during acute exposures (~20-25 seconds) to weightlessness (s) and partial gravity during parabolic flight (t). Several mechanical countermeasures that might mitigate cerebral outflow abnormalities during weightlessness have been evaluated in spaceflight (a, u) and spaceflight analogs (r, v), such as lower body negative pressure, venous occlusion thigh cuffs (VTC), and an impedance threshold devices. VTCs currently are used by astronauts during the early phases of a mission to manage symptoms of the headward fluid shift (u) and are being assessed as a countermeasure for Spaceflight-Associated Neuro-ocular Syndrome and evaluated for their potential influence on IJV flow.

4. References

a) Marshall-Goebel K, Laurie SS, Alferova IV, Arbeille P, Auñón-Chancellor SM, Ebert DJ, Lee SMC, Macias BR, Martin DS, Pattarini JM, Ploutz-Snyder R, Ribeiro LC, Tarver WJ, Dulchavsky SA, Hargens AR, Stenger MB. Assessment of Jugular Venous Blood Flow Stasis and Thrombosis During Spaceflight. JAMA Netw Open 2: e1915011, 2019. doi:10.1001/jamanetworkopen.2019.15011.

b) Auñón-Chancellor SM, Pattarini JM, Moll S, Sargsyan A. Venous Thrombosis during Spaceflight. N Engl J Med 382: 89–90, 2020. doi: 10.1056/NEJMc1905875.

c) Drakos P, Ford BC, Labropoulos N. A systematic review on internal jugular vein thrombosis and pulmonary embolism. Journal of Vascular Surgery: Venous and Lymphatic Disorders 8: 662–666, 2020. doi: 10.1016/j.jvsv.2020.03.003.

d) Heit JA. The epidemiology of venous thromboembolism in the community:

implications for prevention and management. J Thromb Thrombolysis 21: 23–29, 2006. doi: 10.1007/s11239-006-5572-y.

e) Pavela J, Sargsyan A, Bedi D, Everson A, Charvat J, Mason S, Johansen B, Marshall- Goebel K, Mercaldo S, Shah R, Moll S. Surveillance for jugular venous thrombosis in astronauts. Vasc Med 27: 365–372, 2022. doi: 10.1177/1358863X221086619.

f) Levasseur S, Purvis N, Trozzo S, Chung SH, Ades M, Drudi LM. Venous Thromboembolism in Exploration Class Human Spaceflight. Aerosp Med Hum Perform 95: 45–53, 2024. doi: 10.3357/AMHP.6290.2024.

g) Harris K, Laws JM, Elias A, Green DA, Goswami N, Jordan J, Kamine TH, Mazzolai L, Petersen LG, Winnard AJ, Weber T. Search for Venous Endothelial Biomarkers Heralding Venous Thromboembolism in Space: A Qualitative Systematic Review of Terrestrial Studies [Online]. Frontiers in Physiology 13, 2022.

https://www.frontiersin.org/article/10.3389/fphys.2022.885183 [10 May 2022].

h) Harris KM, Arya R, Elias A, Weber T, Green DA, Greaves DK, Petersen LG, Roberts L, Kamine TH, Mazzolai L, Bergauer A, Kim DS, Olde Engberink RH, zu Eulenberg P, Grassi B, Zuccarelli L, Baldassarre G, Tabury K, Baatout S, Jordan J, Blaber AP, Choukér A, Russomano T, Goswami N. Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now? npj Microgravity 9:

1–7, 2023. doi: 10.1038/s41526-023-00260-9.

i) Harris KM, Weber T, Greaves D, Green DA, Goswami N, Petersen LG. Going against the flow: are venous thromboembolism and impaired cerebral drainage critical risks for spaceflight? J Appl Physiol (1985) 132: 270–273, 2022. doi:

10.1152/japplphysiol.00425.2021.

j) Kim DS, Vaquer S, Mazzolai L, Roberts LN, Pavela J, Watanabe M, Weerts G, Green DA. The effect of microgravity on the human venous system and blood coagulation:

a systematic review. Exp Physiol 106: 1149–1158, 2021. doi: 10.1113/EP089409.

k) Zwart SR, Auñón-Chancellor SM, Heer M, Melin MM, Smith SM. Albumin, oral contraceptives, and venous thromboembolism risk in astronauts. J Appl Physiol (1985) 132: 1232–1239, 2022. doi: 10.1152/japplphysiol.00024.2022.

l) Elias A, Weber T, Green DA, Harris KM, Laws JM, Greaves DK, Kim DS, Mazzolai- Duchosal L, Roberts L, Petersen LG, Limper U, Bergauer A, Elias M, Winnard A, Goswami N. Systematic review of the use of ultrasound for venous assessment and venous thrombosis screening in spaceflight. npj Microgravity 10: 1–17, 2024. doi:

10.1038/s41526-024-00356-w.

m) Limper U, Jordan J. Neck-vein thrombosis during spaceflight. British Journal of Clinical Pharmacology n/a, [date unknown]. doi: 10.1002/bcp.70300.

n) Limper U, Tank J, Ahnert T, Maegele M, Grottke O, Hein M, Jordan J. The thrombotic risk of spaceflight: has a serious problem been overlooked for more than half of a century? .

o) Jain V, Ploutz-Snyder R, Young M, Charvat JM, Wotring VE. Potential Venous Thromboembolism Risk in Female Astronauts. Aerosp Med Hum Perform 91: 432– 439, 2020. doi: 10.3357/AMHP.5458.2020.

p) Lan M, Phillips SD, Archambault-Leger V, Chepko AB, Lu R, Anderson AP, Masterova KS, Fellows AM, Halter RJ, Buckey JC. Proposed mechanism for reduced jugular vein flow in microgravity. Physiol Rep 9: e14782, 2021. doi: 10.14814/phy2.14782.

q) Lan M, Van Akin M, Anderson A, Buckey JC. Microgravity-induced reduced jugular vein flow is more pronounced on the non-dominant side. Acta Astronautica 198:

746–755, 2022. doi: 10.1016/j.actaastro.2022.05.048.

r) Laurie SS, Lytle JR, Pickering SK, Poczatek MJ, Lee SMC, Pardon LP, Miller AE, Martin DS, Mulder E, Moestl S, Pesta D, Frett T, Stern C, Tank J, Hoenemann J-N, Sadda S, Karanjia R, Marshall-Goebel K, Young M, Cole CW, Huang AS, Macias BR. Daily use of countermeasures to prevent headward fluid shifts throughout 30 days of strict head-down tilt bed rest. J Appl Physiol (1985) 139: 394–413, 2025. doi:

10.1152/japplphysiol.00635.2024.

s) Marshall-Goebel K, Lee SMC, Lytle JR, Martin DS, Miller CA, Young M, Laurie SS, Macias BR. Jugular venous flow dynamics during acute weightlessness. Journal of Applied Physiology 136: 1105–1112, 2024. doi: 10.1152/japplphysiol.00384.2023.

t) Lytle JR, Miller AE, Martin DS, Miller CA, Young M, Laurie SS, Macias BR, Lee SMC.

Jugular Venous Flow Dynamics during Acute Weightlessness and Partial Gravity in Parabolic Flight. J Appl Physiol, In press. 10.1152/japplphysiol.00032.2025

u) Hamilton DR, Sargsyan AE, Garcia K, Ebert DJ, Whitson PA, Feiveson AH, Alferova IV, Dulchavsky SA, Matveev VP, Bogomolov VV, Duncan JM. Cardiac and vascular responses to thigh cuffs and respiratory maneuvers on crewmembers of the International Space Station. J Appl Physiol 112: 454–462, 2012. doi:

10.1152/japplphysiol.00557.2011.

v) Marshall-Goebel K, Macias BR, Laurie SS, Lee SMC, Ebert DJ, Kemp DT, Miller AE, Greenwald SH, Martin DS, Young M, Hargens AR, Levine BD, Stenger MB.

Mechanical countermeasures to headward fluid shifts. J Appl Physiol (1985) 130:

1766–1777, 2021. doi: 10.1152/japplphysiol.00863.2020.

w) Abercromby A, Baumann D, Berdich D, Broyan J, McCoy T, Watkins S, Zapp N.

NASA’s top human system research and technology needs for Mars. Acta Astronautica 228: 931–939, 2025. doi: 10.1016/j.actaastro.2024.11.001.

x) Buckey JC Jr. Preparing for Mars: the physiologic and medical challenges. Eur J Med Res 4: 353–356, 1999.

5. Additional Resources

Office of the Chief Medical Officer Technical Brief on Venous Thrombosis:

https://www.nasa.gov/wp-content/uploads/2026/01/ochmo-mtb-007-venous-thrombosis-in-spaceflight.pdf

HRE-HM Priorities for Exploration Enabling Science – 2025 (ESA-HRE-HM-MOP-TN-0001) https://ideas.esa.int/apps/IMT/UploadedFiles/00/f_7ee71f64e26768afe2158662aa5f55 63/Annex_3_ESA_HRE- HM_MedOps__Priorities_for_Exploration_Enabli.pdf?v=1773285897

Operations-focused Venous Thrombosis Strategic Roadmap (ESA-HRE-HM-MOP-TN- 0002) https://ideas.esa.int/apps/IMT/UploadedFiles/00/f_ceaaeedc8f3a6aa9473dcacecbacd 134/Annex_2_ESA_Operations- Focused_Uncommon_Venous_Thrombosis_St.pdf?v=1773285897

Existing data from previous NASA spaceflight missions are available through the NASA Life Sciences Portal: https://www.nasa.gov/hrp/nlsp/ https://www.nasa.gov/wp-content/uploads/2026/01/ochmo-mtb-007-venous-thrombosis-in-spaceflight.pdf https://www.nasa.gov/wp-content/uploads/2026/01/ochmo-mtb-007-venous-thrombosis-in-spaceflight.pdf https://ideas.esa.int/apps/IMT/UploadedFiles/00/f_7ee71f64e26768afe2158662aa5f5563/Annex_3_ESA_HRE-HM_MedOps__Priorities_for_Exploration_Enabli.pdf?v=1773285897 https://ideas.esa.int/apps/IMT/UploadedFiles/00/f_7ee71f64e26768afe2158662aa5f5563/Annex_3_ESA_HRE-HM_MedOps__Priorities_for_Exploration_Enabli.pdf?v=1773285897 https://ideas.esa.int/apps/IMT/UploadedFiles/00/f_7ee71f64e26768afe2158662aa5f5563/Annex_3_ESA_HRE-HM_MedOps__Priorities_for_Exploration_Enabli.pdf?v=1773285897 https://ideas.esa.int/apps/IMT/UploadedFiles/00/f_ceaaeedc8f3a6aa9473dcacecbacd134/Annex_2_ESA_Operations-Focused_Uncommon_Venous_Thrombosis_St.pdf?v=1773285897 https://ideas.esa.int/apps/IMT/UploadedFiles/00/f_ceaaeedc8f3a6aa9473dcacecbacd134/Annex_2_ESA_Operations-Focused_Uncommon_Venous_Thrombosis_St.pdf?v=1773285897 https://ideas.esa.int/apps/IMT/UploadedFiles/00/f_ceaaeedc8f3a6aa9473dcacecbacd134/Annex_2_ESA_Operations-Focused_Uncommon_Venous_Thrombosis_St.pdf?v=1773285897 https://www.nasa.gov/hrp/nlsp/

6. The Human Research Program

The Human Research Program investigates and mitigates the highest risks to astronaut health and performance in exploration missions. The goal of the HRP is to provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration, and to ensure safe and productive human spaceflight. The scope of these goals includes both the successful completion of exploration missions and the preservation of astronaut health over the life of the astronaut.

HRP has developed an Integrated Research Plan (IRP) to describe the requirements and notional approach to understanding and reducing the risks to human health and performance. The IRP describes the Program’s research activities that are intended to address the needs of human space exploration and serve HRP customers. The IRP illustrates the HRP’s research plan through the timescale of exploration missions of extended duration.

The Human Research Roadmap (https://humanresearchroadmap.nasa.gov) is a web-based version of the IRP that allows users to search HRP risks, gaps, and tasks.

https://humanresearchroadmap.nasa.gov/