Risk of Venous Thromboembolism During Spaceflight

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Preparations for Next Moonwalk Simulations Underway (and Underwater)

In-person participants (L-R) – Back row: Jason Lytle, Stuart Lee, Eric Bershad, Ashot Sargsyan, Aaron Everson, Philip Wells, Sergi Vaquer Araujo, Steven Grover, John A. Heit, Mehdi Shishehbor, Laura Bostick; Middle row: Sarah Childress Taoufik, Stephan Moll, Brandon Macias, Kristin Coffey, Ann-Kathrin Vlacil, Dave Francisco; Front row: James Pavela, Doug Ebert, Kathleen McMonigal, Esther Kim, Emma Hwang; Not pictured: Tyson Brunstetter, J. D. Polk
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NASA

In October 2024, NASA’s Office of the Chief Health and Medical Officer (OCHMO) initiated a working group to review the status and progress of research and clinical activities intended to mitigate the risk of venous thromboembolism (VTE) during spaceflight. The working group took place over two days at NASA’s Johnson Space Center; a second meeting on the topic was held in December 2024 at the European Space Agency (ESA) facility in Cologne, Germany.

The working group was assembled from internal NASA subject matter experts (SMEs), the NASA OCHMO Standards Team, NASA and ESA stakeholders, and external SMEs, including physicians and medical professionals from leading universities and medical centers in the United States and Canada.

Background

Spaceflight Venous Thrombosis (SVT)

Spaceflight Venous Thrombosis (SVT) refers to a phenomenon experienced during spaceflight in which a thrombus (blood clot) forms in the internal jugular vein (and/or associated vasculature) that may be symptomatic (thrombus accompanied by, but not limited to, visible internal jugular vein swelling, facial edema beyond “nominal” spaceflight adaptation, eyelid edema, and/or headache) or asymptomatic. Obstructive thrombi have been identified in a very small number of crewmembers, as shown in the figure below.

Note that the figure below is for illustrative purposes only; locations are approximate, and size is not to scale.

Approximate location of identified thrombi in crewmembers.
Source: Modified from Cerebral Sinus Venous Thrombosis – University of Colorado Denver

With treatment, crewmembers were able to complete their mission, and anticoagulants were discontinued several days prior to landing to minimize the risk of bleeding in the event of a traumatic injury. Some thromboses completely resolved post landing, and some required additional treatment.

Pathophysiology of Venous Thromboembolism (VTE)

The proposed pathogenesis of VTE is referred to as Virchow’s triad and suggests that VTE occurs as the result of:

  1. Alterations in blood flow (i.e., stasis),
  2. Vascular endothelial injury/changes, and/or,
  3. Alterations in the constituents of the blood leading to hypercoagulability (i.e., hereditary predisposition or acquired hypercoagulability).

Note: pathophysiology are the changes that occur during a disease process; hypercoagulability is the increased tendency to develop blood to clots.

VTE, OCHMO, medical, health, venous thrombosis, blood clots, Virchow
The Virchow’s triad of risk factors for venous thrombosis.
Bouchnita, 2017

Blood stasis, or venous stasis, refers to a condition in which the blood flow in the veins slows down which leads to pooling in the veins. This slowing of the blood may be due to vein valves becoming damaged or weak, immobility, and/or the absence of muscular contractions. Associated symptoms include swelling, skin changes, varicose veins, and slow-healing sores or ulcers. In terrestrial medicine, venous thrombosis is typically caused by damaged or weakened vein valves, which can be due to many factors, including aging, blood clots, varicose veins, obesity, pregnancy, sedentary lifestyle, estrogen use, and hereditary predisposition.

Spaceflight Considerations

Altered Venous Blood Flow and Spaceflight Associated Neuro-ocular Syndrome

In addition to the terrestrial risk factors of VTE, there are physiological changes associated with spaceflight that are hypothesized to potentially play a role in the development of VTE in weightlessness. Specifically, researchers have explored the effects of the microgravity environment and subsequent observed headward fluid shifts that occur, and the potential impact on blood flow. Crewmembers onboard the International Space Station (ISS) experience weightlessness due to the microgravity environment and thus experience a sustained redistribution of bodily fluids from the legs toward the head. The prolonged headward fluid shifts during weightlessness results in facial puffiness, decreased leg volume, increased cardiac stroke volume, and decreased plasma volume.

Crewmembers have also experienced altered blood flow during spaceflight, including retrograde venous blood flow (RVBF) (the backflow of venous blood towards the brain) or stasis (a stoppage or slowdown in the flow of blood). While the causes of the observed stasis and retrograde blood flow in spaceflight participants is not well understood, the potential clinical significance of the role it may have in the development of thrombus formation warrants further investigation.

doppler, VTE, SANS, venous thrombosis, medical, health
Doppler imaging of a retrograde flow in the left internal jugular vein.
Yan & Seow, 2009

Other physiological concerns affected by fluid shifts are being studied to consider if any relation to VTE exists. Chronic weightlessness can cause bodily fluids such as blood and cerebrospinal fluid to move toward the head, which can lead to optic nerve swelling, folds in the retina, flattening of the back of the eye, and swelling in the brain. This collection of eye and brain changes is called “spaceflight associated neuro-ocular syndrome,” or SANS. Some astronauts only experience mild changes in space, while others have clinically significant outcomes. The long-term health outcome from these changes is unknown but actively being investigated. The risk of developing SANS is higher during longer-duration missions and remains a top research priority for scientists ahead of a Mars mission.

Conclusions and Further Work

Based on expert opinion and the assessment of the risk factors for thrombosis, an algorithm was developed to provide guidance for in-mission assessment and treatment of thrombus formation in weightlessness. The algorithm is based on early in-flight ultrasound testing to determine the flow characteristic of the left internal jugular vein and associated vasculature.

VTE, veinous thrombosis
NASA

Working Group Recommendations

The working group recommended several areas for further investigation to assess feasibility and potential to mitigate the risk of thrombosis in spaceflight:

  • Improved detection capabilities to identify when a thrombus has formed in-flight,
  • Pathophysiology/factors leading to thrombi formation during spaceflight,
  • Countermeasures and treatment

For more information on the working group meeting and a complete list of references, please see the Risk of Venous Thromboembolism (VTE) During Spaceflight Summary Report.

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