The effect of microgravity on the human venous system and blood coagulation: a systematic review

Abstract

Recently, an internal jugular venous thrombus was identified during spaceflight, but whether microgravity induces venous and/or coagulation pathophysiology, and thus, an increased risk of venous thromboembolism (VTE) is unclear. Therefore, a systematic (Cochrane compliant) review was performed of venous system or coagulation parameters in actual spaceflight (microgravity) or ground-based analogues in PubMed, MEDLINE, Ovid EMBASE, Cochrane Library, European Space Agency, National Aeronautics and Space Administration, and Deutsches Zentrum für Luftund Raumfahrt databases. Seven-hundred and eight articles were retrieved, of which 26 were included for evaluation with 21 evaluating venous, and five coagulation parameters. Nine articles contained spaceflight data, whereas the rest reported ground-based analogue data. There is substantial variability in study design, objectives and outcomes. Yet, data suggested cephalad venous system dilatation, increased venous pressures and decreased/reversed flow in microgravity. Increased fibrinogen levels, presence of thrombin generation markers and endothelial damage were also reported. Limited human venous and coagulation system data exist in spaceflight, or its analogues. Nevertheless, data suggest spaceflight may induce an enhanced coagulation state in the cephalad venous system, as a consequence of changes in venous flow, distension, pressures, endothelial damage and possibly hypercoagulability.Whether such changes precipitate an increased VTE risk in spaceflight remains to be determined.

The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model

“…Since the beginning of the age of space travel in the 1960s, the question of if and how microgravity (µ g ) influences whole organisms and cells has been one major focus in the field of space medicine and related disciplines. Over the years, it has become clear that µ g can induce a multitude of health risks in astronauts, including bone loss, muscle atrophy, cardiac atrophy, visual impairment, increased intracranial pressure, cardiovascular complications, skin problems, increased infection risk, impaired immune system, motion sickness, and orientation problems (besides the radiation-induced effects during space travel, such as an increased risk for cancer or cataracts) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ].…”

Going against the flow: are venous thromboembolism and impaired cerebral drainage critical risks for spaceflight?

“…They reported an alarming observation of stagnation and even reversal of the cerebral venous outflow in 6 of 11 astronauts, suggesting that spaceflight may cause venous blood to flow from the central veins through the internal jugular vein into the brain (2). Such venous retrograde flow patterns have never been reported in ground-based analogues nor in actual weightlessness (10), and warrant further consideration in terms of physiological consequences and the methodology used to quantify venous flow.…”

“…Limitations of currently available ultrasound technology and operator expertise in-flight introduce uncertainties in interpretation of venous flow data. These limitations are easier to overcome in terrestrial analogues or clinical trials and may explain why retrograde IJV flow has not been seen before (10).…”

“…While astronaut selection ensures an overall low medical risk population, headward fluid shift, inactivity and associated venous stasis may increase the risk of blood clot formation in weightlessness( 5). Virchow's triad summarizes the three conventional VT risk factors: altered blood flow/stasis, vascular wall injury, and hypercoagulability (10). Venous stasis in the internal jugular vein (IJV), combined with vessel-wall distention could arguably constitute spaceflight associated risk factors for cephalad thrombosis (5,11,12).…”

MSCs in Space: Mesenchymal Stromal Cell Therapeutics as Enabling Technology for Long-Distance Manned Space Travel

“…As outlined above, the hostile tissue environment encountered by MSCs after in vivo delivery promotes cellular apoptosis and triggering of IBMIR with concomitant therapeutic cell graft destruction and rejection, which is furthermore affected by patient-specific parameters [2•, 5, 36]. Spaceflight and microgravity may alter coagulation parameters, promote hypercoagulability, and induce venous and/or coagulation pathology, particularly in the cephalad venous system [111]. This may be associated with altered/increased triggering of IBMIR responses to systemically infused TF/ CD142-bearing cell products and thus altered safety profiles, cell persistence, and functionality.…”