Coagulation Changes during Presyncope and Recovery

Abstract

Orthostatic stress activates the coagulation system. The extent of coagulation activation with full orthostatic load leading to presyncope is unknown. We examined in 7 healthy males whether presyncope, using a combination of head up tilt (HUT) and lower body negative pressure (LBNP), leads to coagulation changes as well as in the return to baseline during recovery. Coagulation responses (whole blood thrombelastometry, whole blood platelet aggregation, endogenous thrombin potential, markers of endothelial activation and thrombin generation), blood cell counts and plasma mass density (for volume changes) were measured before, during, and 20 min after the orthostatic stress. Maximum orthostatic load led to a 25% plasma volume loss. Blood cell counts, prothrombin levels, thrombin peak, endogenous thrombin potential, and tissue factor pathway inhibitor levels increased during the protocol, commensurable with hemoconcentration. The markers of endothelial activation (tissue factor, tissue plasminogen activator), and thrombin generation (F1+2, prothrombin fragments 1 and 2, and TAT, thrombin-antithrombin complex) increased to an extent far beyond the hemoconcentration effect. During recovery, the markers of endothelial activation returned to initial supine values, but F1+2 and TAT remained elevated, suggestive of increased coagulability. Our findings of increased coagulability at 20 min of recovery from presyncope may have greater clinical significance than short-term procoagulant changes observed during standing. While our experiments were conducted in healthy subjects, the observed hypercoagulability during graded orthostatic challenge, at presyncope and in recovery may be an important risk factor particularly for patients already at high risk for thromboembolic events (e.g. those with coronary heart disease, atherosclerosis or hypertensives).

Higher levels of von Willebrand factor in patients with syncope due to orthostatic hypotension

“…Thus, the SYSTEMA cohort, being a real-life patient population, is more representative of the population-based cohorts included in previous epidemiological studies investigating relations between orthostatic hypotension and cardiovascular events. Moreover, in the aforementioned studies [10,11], orthostatic hypotension has not been systematically assessed. Consequently, the orthostatic stress model used in healthy volunteer-based studies cannot satisfactorily explain why patients with orthostatic hypotension differ in regard to cardiovascular risk from the normal population.…”

“…Orthostatic stress leads to increased intravascular pressure and enhances endothelial activation [10,11,19,20]. Under normal conditions, blood vessel walls are covered by a negatively charged layer of healthy endothelial cells.…”

“…The relationship between orthostatic hypotension and cardiovascular events is not completely understood, which precludes prevention and treatment. Small studies conducted in healthy individuals have indicated that orthostatic stress may trigger the coagulation system by fluid shift and increased intravascular pressures, resulting in endothelial cell activation, increased plasma protein concentrations, expression of tissue factor, and release of procoagulants from endothelial Weibel-Palade bodies [10,11]. In these studies, procoagulants, such as fibrinogen, FVIII, and VWF were elevated during standing.…”

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

“…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).…”

Endothelial function in vasovagal syncope

“…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. Orthostatic stress has to be considered as an important risk factor for hypotension susceptibility, particularly in these patients in whom the activation of coagulation during orthostatic challenge persists after the challenge [19].…”