Relationship Between Psychological Distress and Endogenous Anticoagulants in Patients With a Previous Venous Thromboembolic Event

Abstract

Psychological distress, particularly anxiety and depression, has been associated with a prothrombotic state. However, the relationship between psychosocial factors and endogenous anticoagulants protein S (PS) and protein C (PC) has not previously been investigated. We explored the association between psychological distress, PS, and PC in patients with an objectively diagnosed venous thromboembolic event (VTE). We investigated 126 consecutively enrolled patients ≥3 months after VTE (ie, deep venous thrombosis and/or pulmonary embolism) and ≥1 month of discontinuation of oral anticoagulants. Approximately 10 days before blood collection for thrombophilia workup, anxiety and depression scores were assessed using the Hospital Anxiety and Depression scale (HADS). Protein C and S were determined by routine laboratory assays. After controlling for demographic and medical factors, PC, as measured by the PC-activated partial thromboplastin time (aPTT) method and the PC-chromatin substrate method, was positively associated with psychological distress (sum of anxiety plus depression symptoms; P ≤ .027), anxiety (P ≤ .055), and depression (P ≤ .031), explaining between 3% and 6% of the variance. Total PS antigen showed a direct relationship with psychological distress (P = .025) and depression (P = .005), explaining 5% and 7% of respective variances. Free PS showed a positive association with depression (P = .046), explaining 3% of the variance. Anxiety showed no independent association with either PS measure. Psychological distress is independently associated with enhanced endogenous anticoagulant potential. This might reflect a counterregulatory mechanism to outweigh the previously observed hypercoagulability in individuals under chronic stress and with elevated symptoms of anxiety and depression.