Effects of Repeated Bouts of Exercise on the Hemostatic System

Abstract

Physical activity is beneficial for health, for example, by lowering the risk of cardiovascular events. However, vigorous exercise is associated with the occurrence of thromboembolic events and sudden cardiac death, in particular in untrained individuals. Whereas acute exercise is known to cause a hypercoagulable state, repeated exposure to (strenuous) exercise by means of training may actually condition the hemostatic response to exercise. To date, the effects of exercise training on blood coagulability and the underlying mechanisms have yet to be fully discerned. In this review, the authors provide an overview of existing literature on how training programs and training status influence hemostasis in healthy individuals. Furthermore, they present data of a pilot study in which we studied the effects of repetitive submaximal intensity cycling on procoagulant and anticoagulant processes. It is known that factor VIII (FVIII) and von Willebrand factor (VWF) increase after exercise, but we found that this increase in FVIII and VWF (antigen, propeptide, and VWF in active conformation) was smaller on each of three subsequent days, suggesting either adaptation of endothelial activation or exhaustion of endothelial VWF supplies. With respect to thrombin generation, elevated FVIII significantly increased the thrombin generation peak but not the endogenous thrombin potential. In contrast, platelet activation in terms of P-selectin expression after stimulation with protease-activated receptor-1 and glycoprotein VI agonists decreased after exercise and did not recover, indicating exhaustion of the platelet response to repetitive exercise.

Sources and solutions for spurious test results in coagulation

“…Alterations in hematocrit due to various conditions, such as anemia, dehydration, and polycythemia, may lead to inappropriate results (ie, PFA‐100, inappropriate citrate concentration) . Exercise may lead to increased procoagulant factors, as well as increased von Willebrand factor . Patients may also have extensive hemolysis, hyperbilirubinemia, or lipemia that can interfere with optical clot‐based detection systems .…”

“…18 Exercise may lead to increased procoagulant factors, 19 as well as increased von Willebrand factor. 20 Patients may also have extensive hemolysis, hyperbilirubinemia, or lipemia that can interfere with optical clot-based detection systems. 19,21 Finally, patients may be on medications, such as heparin or direct oral anticoagulants, which can alter the results of the assay.…”

“…If the patient's current lifestyle and/or disease state is known to affect hemostasis testing AND can be modified, patients should be deferred from testing until the issue is resolved or discontinued. 19,20,22,23 In order to manage the effects of medications on coagulation testing, the laboratory should have a list of such medications made available to clinicians and laboratorians. In the presence of such medications, the laboratory should either 1 not perform the testing or 2 make sure that a comment is added to the reported result (Table 1).…”

Analytical characterization and reference interval of an enzyme-linked immunosorbent assay for active von Willebrand factor

“…Increased circulating active VWF levels may also be present in other conditions associated with infection and/or inflammation, for instance in chronic kidney disease (submitted). Moreover, using the current assay, we found that active VWF levels in healthy individuals increase following strenuous exercise [43]. Quantification of active VWF in a variety of diseases could provide valuable pathophysiological insight for diagnosis and development of new treatment strategies.…”

Hemostasis in Exercise and the Athlete

“…It is well known that physical activity is beneficial for health and can lower the risk of cardiovascular disease [1][2][3] ; however, vigorous exercise is associated with thromboembolic and sudden cardiac events, particularly in untrained individuals. Exploring the concept of transitioning from risk to benefit, in the first review of this issue (by van der Vorm et al), 4 the authors provide an overview of existing literature on how training programs and training status influence hemostasis in healthy individuals. Furthermore, pilot study data are presented describing the effects of repetitive submaximal intensity cycling on procoagulant and anticoagulant processes in physically fit individuals.…”