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

Abstract

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.