Search for Venous Endothelial Biomarkers Heralding Venous Thromboembolism in Space: A Qualitative Systematic Review of Terrestrial Studies

Abstract

Background: The recent discovery of a venous thrombosis in the internal jugular vein of an astronaut has highlighted the need to predict the risk of venous thromboembolism in otherwise healthy individuals (VTE) in space. Virchow’s triad defines the three classic risk factors for VTE: blood stasis, hypercoagulability, and endothelial disruption/dysfunction. Among these risk factors, venous endothelial disruption/dysfunction remains incompletely understood, making it difficult to accurately predict risk, set up relevant prophylactic measures and initiate timely treatment of VTE, especially in an extreme environment.Methods: A qualitative systematic review focused on endothelial disruption/dysfunction was conducted following the guidelines produced by the Space Biomedicine Systematic Review Group, which are based on Cochrane review guidelines. We aimed to assess the venous endothelial biochemical and imaging markers that may predict increased risk of VTE during spaceflight by surveying the existing knowledge base surrounding these markers in analogous populations to astronauts on the ground.Results: Limited imaging markers related to endothelial dysfunction that were outside the bounds of routine clinical practice were identified. While multiple potential biomarkers were identified that may provide insight into the etiology of endothelial dysfunction and its link to future VTE, insufficient prospective evidence is available to formally recommend screening potential astronauts or healthy patients with any currently available novel biomarker.Conclusion: Our review highlights a critical knowledge gap regarding the role biomarkers of venous endothelial disruption have in predicting and identifying VTE. Future population-based prospective studies are required to link potential risk factors and biomarkers for venous endothelial dysfunction to occurrence of VTE.

Systematic review of the use of ultrasound for venous assessment and venous thrombosis screening in spaceflight

“… In spaceflight, the diagnostic accuracy of terrestrial US criteria is unknown. Slow, stagnant, retrograde blood flow, especially in the IJV, due to volume overload and elevated venous pressures secondary to the classic cephalic fluid shift 8 , 56 , 65 , may mimic the aspects encountered in venous thrombosis. It is important to improve V-US scanning conditions by decreasing central venous pressure and venous congestion through the effect of venous interventions such as thigh cuffs, LBNP, Mueller manoeuvres and contralateral IJV compression.…”

“…The third issue is the lack of studies on diagnostic accuracy and diagnostic management in patients with clinically suspected DVT in space. Therefore, the optimal venous ultrasound (V-US) criteria to rule-out and conversely rule-in the diagnosis of DVT in space remain to be defined, as is the case with clinical presentation including VTE risk factors 7 , and D-dimer and endothelial biomarkers 8 .…”

Impact of Increasing Lower Body Negative Pressure and Its Abrupt Release on Left Ventricular Hemodynamics in Anesthetized Pigs

“…Hemodynamic assessments of LBNP application in previous studies have been largely carried out non-invasively [ 6 ], commonly using pulse wave forms or Doppler probes, and therefore limiting their mechanistic accuracy. Furthermore, in human studies the occurrence of syncope due to reduced cerebral perfusion has been reported frequently [ 18 , 19 ]. However, the impact of hazardous low systemic pressures (MAP < 30 mmHg) on ventricular function and mechano-energetics remains largely unknown.…”

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

“…Over the course the topical team's tenure, we have published on the likelihood of flow abnormalities in contributing to VT formation 12 , endothelial disruption related risks of VT 46 , and diagnostic modalities for VT in space (in review). We found that current tools on board the ISS are insufficient to characterize blood flow patterns that may contribute to clot formation and that there are no validated biomarkers that reliably predict increased likelihood of VT formation in otherwise healthy people.…”

“…We do not have a valid spaceflight compatible imaging diagnosis pathway.Determination of a gold-standard diagnostic algorithm/pathway (biomarkers and imaging). This involves progressing existing work on diagnostic methods (U/S and biomarkers) for VT during spaceflight46 . The ultrasound criteria to rule-out and rule-in the diagnosis of VT in spaceflight must be established.…”