Anxiety-Related Bleeding and Thrombosis

Abstract

Anxiety, a normal response to stressful situations, is characterized by increased levels of factor VIII, fibrinogen, and von Willebrand factor, and by enhanced platelet aggregability. One would expect acute anxiety to be a prothrombotic state, but since acute mental stress induces tissue plasminogen activator (tPA) release from endothelial and chromaffin cells, fibrinolysis counteracts procoagulant stimuli. It could be said that procoagulant changes accompanying the fight-or-flight response reduce the risk of bleeding in case of potential injuries, while activation of fibrinolysis counteracts activation of hemostasis to prevent intravascular thrombus formation before injuries occur. Acutely anxious patients are prone to bleeding or thrombosis when the balance between hypercoagulation and hyperfibrinolysis is disturbed. Acute anxiety not only increases the risk of bleeding in hemophilia or von Willebrand disease, but many reports have shown that anxiolytic interventions such as hypnosis are effective in controlling bleeding in hemostatic disorders. The pathogenesis of cardiovascular and thrombotic diseases in highly anxious patients is multifactorial. An important element is α-adrenergic vasoconstriction, which increases viscosity due to leakage of intravascular fluid into the interstitium, and also causes hypertension, favoring plaque rupture. Paradoxical as it may seem, over secretion of tPA may increase cardiovascular risk. This is because tPA degrades the extracellular matrix, causing vascular stiffness that increases cardiac workload, and thus oxygen requirements. Anxious patients with conditions associated with increased plasminogen activator inhibitor-1 levels, such as depression or postprandial hyperinsulinemia, are at high risk of thrombosis. Postprandial hyperinsulinemia may result from consumption of high-carbohydrate foods, considered anxiolytic, combined with a sedentary life, which is common among anxious individuals. Preliminary evidence suggests that high anxiety combined with either depression or a lifestyle that results in hyperinsulinemia has an important role in the pathogenesis of thrombotic events currently classified as unprovoked.

Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis

“…Nicotine affects the secretion function of ECs, leading to platelet adhesion and aggregation, by increasing TF and TXA2 expression, reducing prostaglandin I-2 expression, and NPY combined with those to promote thrombosis. NPY not only directly stimulates vasoconstriction associated with platelet aggregation to promote thrombosis ( 84 , 85 ), but also induces anxiety ( 31 , 86 ), which contributes substantially to platelet activation ( 32 ) by activating Y2R in the hypothalamus and striatum. Therefore, nicotine and NPY play a combined role in promoting pathological angiogenesis and thrombosis.…”

d-Dimer Elevation in Asymptomatic Vascular Disease After Venlafaxine Administration

“…Lederbogen et al 6 conclude that major depression is associated with increased platelet aggregability, which seems to persist even under a marked improvement in depressive symptom. In a study by Hoirisch-Clapauch et al, 7 tissue plasminogen activator and plasminogen activator inhibitor 1 imbalance may play an important role in pathophysiology of mental and thromboembolic disorders. Tissue plasminogen activator facilitates clot dissolution and participates in several brain functions, including response to stress, learning, and memory 7 .…”

“…In a study by Hoirisch-Clapauch et al, 7 tissue plasminogen activator and plasminogen activator inhibitor 1 imbalance may play an important role in pathophysiology of mental and thromboembolic disorders. Tissue plasminogen activator facilitates clot dissolution and participates in several brain functions, including response to stress, learning, and memory 7 . Parkin et al 8 showed that women with antidepressant use had a significantly higher risk of VTE than women who reported neither depression nor use of psychotropic drugs.…”

Impact of stress on hemostasis: A review

“…Эволюционная интерпретация Кэнноном этих наблюдений заключалась в том, что «быстрая коагуляция может разумно рассматриваться как пример адаптивной реакции, полезной для организма при травме, которая может последовать за борьбой, которую может вызвать страх или ярость». Со времени новаторской работы Кэннона о реакции человека на стресс («сражайся или беги») накоплено множество доказательств из натуралистических, экспериментальных и механистических исследований, показывающих, что гемостатические реакции на острый психический стресс приводят к гиперкоагуляции [3,4].…”