Orthostatic Hypercoagulability

Abstract

Abstract-Orthostatic stress causes significant plasma shift and raises transmural pressure in lower extremities, resulting in an increase in endothelial activation and plasma proteins concentrations, possibly including coagulation factors. This may lead to activation of the coagulation system during standing. To test this hypothesis, we recruited 18 healthy volunteers (9 females and 9 males; mean age: 25Ϯ1.2 years; body mass index: 21.7Ϯ0.5 kg/m 2 ). Hemodynamics, plasma shift (extrapolated from sequential hematocrit concentration), plasma proteins, and coagulation tests, including procoagulants; fibrinogen, factor V, and factor VIII activity; prothrombin fragments 1 and 2; and endothelial activation-related factors (tissue factor and von Willebrand factor), as well as protein C global pathway, were determined at rest supine and at 15 minutes, 30 minutes, and 60 minutes of still standing. Thirty minutes of standing caused a decrease in plasma volume by 12.0Ϯ0.5% and an increase in plasma protein by 13.0Ϯ0.7%. Fibrinogen, factor V, and factor VIII activity rose by 12.0Ϯ1.2%, 13.0Ϯ1.0%, and 40.0Ϯ6.0% (PϽ0.002 for all), respectively. Prothrombin fragments 1 and 2 were elevated by 150.0Ϯ30.0%. Tissue factor and von Willebrand factor increased by 30.0Ϯ9.0% and 17.4Ϯ51.0% (PϽ0.02 for both), respectively. However, protein C assay results decreased from 0.95Ϯ0.20 to 0.83Ϯ0.16 (PϽ0.001). We hereby introduce a novel physiological mechanism, "orthostatic procoagulation," that should be considered during coagulation tests. Furthermore, it could be extrapolated to the pathophysiology of stasis and venous thromboembolism.

Coagulation changes during lower body negative pressure and blood loss in humans

“…However, it is unclear if markers of coagulation system activation respond similarly during these protocols. Reductions in central blood volume by LBNP (38) or orthostatic stress (10,21,36) activate the coagulation cascade; therefore, it is likely that central hypovolemia during BL elicits comparable changes in coagulation when the degree of central hypovolemia is similar between LBNP and BL.…”

“…The suction applied during LBNP produces a pressure gradient that pulls fluid from the intravascular compartment to the extravascular space in the lower body, resulting in hemoconcentration (5,29,34). Plasma protein concentration and blood viscosity both increase, which creates a procoagulant milieu due to increased interactions between coagulation factors and cellular contributors to coagulation (12,17,21). However, BL has the opposite effect.…”

Tissue Factor and Cardiovascular Disease: Quo Vadis?

“…89,90 Hypertension increases shear stress leading to activation of NFκB and Egr-1, and subsequently to upregulation of TF gene expression. 91,92 Angiotensin-convertingenzyem (ACE) inhibitors downregulate TF expression in vivo, 93 while angiotensin II upregulates it in vascular cells via the angiotensin II type 1 receptor.…”

Endothelial function in vasovagal syncope

“…In 2008, Masoud and colleagues described a novel physiological mechanism, 'orthostatic procoagulation,' in which endothelial-dependent procoagulant and anticoagulant systems are activated during prolonged static standing [18].…”

“…Significant increases in concentration or activity of blood coagulation factors in response to orthostatic stress have been reported [16][17][18]. Cvirn and colleagues reported that the procoagulant effect of orthostatic stress persists for up to 20 min after presyncope, which is the endpoint of cardiovascular stress.…”