The association between seated immobility and local lower-limb venous coagulability in healthy adult volunteers: a simulation of prolonged travel immobility

Abstract

This is the first study to examine the hypothesis that prolonged sitting is associated with procoagulant changes in the local lower-limb venous system. A comparison was made with upper-limb venous changes. Changes in markers of thrombin generation, fibrinolysis, endothelial perturbation and haemoconcentration were analysed as 10 healthy adult male participants sat for 8 h. The change in foot volume was estimated. Subjective venous thromboembolism assessment was undertaken hourly, along with 2-week and 4-week safety follow-up for clinical events. Expected increases in median prothrombin fragments 1 and 2, thrombin-antithrombin complex and D-dimer were not observed in either limb. An increase greater than 45% in the median tissue plasminogen activator and plasminogen activator-1 molar ratio (t-PA/PAI-1), and a decrease greater than 15% in median soluble thrombomodulin were noted in both limbs. Median haematocrit decreased minimally (1%) in the lower limbs, while the foot volume increased by 4%. Subjects experienced vague symptoms after 6 h of sitting, but none developed symptomatic venous thromboembolism. Upper and lower-limb changes in biomarkers did not correlate, except those in t-PA/PAI-1 ratio and plasminogen activator-1. Significant correlation was found between changes in the lower-limb t-PA/PAI-1 ratio and right foot volume. This study originally reveals that even in the lower limbs, prolonged daytime cramped sitting is not associated with significant procoagulant changes in healthy adult male volunteers, and confirms a previous observation that local lower-limb venous changes are not identically reflected in the upper limbs.

Factors Associated With Positive D‐dimer Results in Patients Evaluated for Pulmonary Embolism

“…While immobility is known to be related to PE risk, 15 to the authors’ knowledge, this is the first study to demonstrate an independent association between immobility and D‐dimer positivity. Two prior studies investigated the issue of hypercoagulability during a simulated airplane flight in 10 healthy subjects and one subject who was heterozygous for factor V Leiden and found no association 16,17 . These results are consistent with our finding of no association between recent travel and D‐dimer results.…”

No effect of isolated long‐term supine immobilization or profound prolonged hypoxia on blood coagulation

“…Ansari et al . observed a 22% decrease in F 1 + 2 after an 8‐h sitting period but no change in TAT values. An explanation for these findings is that muscle movement during normal daily activities may lead to a constant level of minute coagulation activation; this is illustrated by studies that showed increased thrombin generation after increased muscle use (i.e., exercise) .…”

“…This finding is supported by a study by Stricker et al [17], who found no difference in D-dimer but reported an 18% decrease in F 1 + 2 after 6 h of prolonged cramped sitting (which even countered the circadian rhythm). Ansari et al [18] observed a 22% decrease in F 1 + 2 after an 8-h sitting period but no change in TAT values. An explanation for these findings is that muscle movement during normal daily activities may lead to a constant level of minute coagulation activation; this is illustrated by studies that showed increased thrombin generation after increased muscle use (i.e., exercise) [19,20].…”

Travel and venous thrombosis: a systematic review

“…Several studies investigated the effect of prolonged immobilization on thrombin generation, but conflicting results were shown [54–67] (Table 4). Stricker et al.…”