How does stress induce hypercoagulability?

From the Guidelines

Stress induces hypercoagulability through multiple physiological pathways, including increased platelet activation and aggregation, elevated levels of clotting factors, and reduced fibrinolysis, as supported by the most recent evidence from 2020 1.

Key Mechanisms

• Activation of the sympathetic nervous system, triggering the release of stress hormones like cortisol, epinephrine, and norepinephrine
• Increased platelet activation and aggregation
• Elevated levels of clotting factors such as fibrinogen and factor VIII
• Reduced fibrinolysis, the body's natural clot-dissolving mechanism
• Endothelial dysfunction, damaging the inner lining of blood vessels and creating a more thrombogenic surface
• Inflammatory cytokines released during stress, promoting tissue factor expression and initiating the coagulation cascade

Clinical Implications

• Chronic stress maintains these pro-thrombotic changes over time, significantly increasing the risk of dangerous blood clots, including deep vein thrombosis and pulmonary embolism
• Stress-induced hypercoagulability explains why periods of intense psychological or physical stress are associated with increased cardiovascular events and thrombotic complications
• Recognition and management of psychosocial stressors should be useful in promoting a healthy lifestyle and preventing cardiometabolic risk, as suggested by the 2020 study 1

Relevant Evidence

• A 2020 study published in the Journal of the American College of Cardiology highlights the importance of considering psychosocial stressors in preventive cardiology care 1
• While older studies, such as the 2006 Mayo Clinic Proceedings article, discuss aspirin and clopidogrel resistance, they do not directly address the relationship between stress and hypercoagulability 1

From the Research

Mechanisms of Stress-Induced Hypercoagulability

• Stress-induced hypercoagulability is an adaptive response to bleeding, mediated by neurohormonal changes, including the sympathetic neural system and the hypothalamic-pituitary-adrenal axis 2
• The stress reaction activates the sympathoadrenal medullary system, resulting in the activation of both the coagulation and fibrinolysis systems, leading to net hypercoagulability 3
• The activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, along with vagal withdrawal, and the effects of catecholamines, cortisol, and vasopressin, are the central mechanisms involved in stress-induced hypercoagulability 4

Clinical Implications of Stress-Induced Hypercoagulability

• Stress-induced hypercoagulability is associated with increased incident risk and poor prognosis for atherosclerotic cardiovascular disease and venous thromboembolism 4
• Individuals with predisposing factors, including atherosclerosis, thrombophilia, or immobilization, may exhibit an increased risk of thrombotic disease during stress 4
• Contextual sociodemographic characteristics, the stress experience, and coping resources additionally modulate the extent of stress-induced hypercoagulability 4

Prevention and Management of Thrombotic Diseases

• Anticoagulant therapy, such as low-molecular-weight heparin (LMWH) or warfarin, is used to prevent and manage thrombotic diseases 5, 6
• The optimal duration of anticoagulant therapy depends on an individual patient's potential risk for recurrence or treatment-associated complications 5, 6
• Research is needed to prove a causal link between chronic stress and hypercoagulability, and to explore its implications for the prevention and management of thrombotic diseases in stressed individuals 4