Table 2.

Pathophysiology/Risk—Gap Analysis and Recommendations.

Gap	Recommendation
We do not know the specific VT risk associated with spaceflight, or the modulating factors of spaceflight that affect risk (ie. length of flight).	Establish the relative risk profile of VT during spaceflight, together with anatomical predilection sites (due to headward fluid shift and other changes). A comprehensive investigation of the whole venous network (peripheral and central vein segments) is essential to clearly distinguish between thrombosis and stasis in spaceflight and to identify potential sites of thrombosis and key areas to screen during future flights.
We do not know the utility of screening potential astronauts for thrombophilia’s or terrestrial VT risk factors.	Evaluate the use of test specifically aimed at evaluating endothelial/microvascular function (e.g., the increase in blood flow in the common femoral artery, determined by Eco-Doppler, during passive leg movements) in the selection of astronauts. Consider routine screening for VT in future travellers. Significant effort must be made to develop state-of-the-art technologies to individualize direct imaging of the thrombus at the level of the peripheral veins (lower and upper limbs) and the central veins (abdomen, pelvis, and thorax). The group recommends that ESA creates a Request for Proposal to further investigate high frame rate ultrasound and 3D motorized probes as next generation diagnostic technology for quantifying blood flow characteristics and possibly predicting a circulation environment where clots might occur. Consider the feasibility of spaceflight for individuals with specific known risk factors (i.e., Factor C/S deficiency, genetic risks).
We do not know the risks or benefits of hormone therapy in female astronauts.	Further assess potential prothrombotic effects of sex hormones during space travel.
We do not know the pathophysiological processes that may underlie symptomatic and asymptomatic VT risk.	Further assess microgravity-specific potential risk factors. Build a database of standard measures (biomarkers and ultrasound flow) to track changes and timeline of changes during analogue trials and in-flight missions.
We do not know the normal range of values in- and immediately post-flight of candidate Earth-based coagulation tests.	Assess prothrombotic biomarkers during spaceflight and in ground-based analogues. Spaceflight testing of coagulation markers and coagulation times is necessary to recommend treatment protocols.