Hypercoagulability Due to Protein S Deficiency in HIV-Seropositive Patients

Background: Thrombosis due to a hypercoagulable state is a serious clinical problem in HIV-infected individuals that can lead to life-threatening thromboembolic phenomenon. Reported causes of thrombophilia in HIV-infected subjects include antiphospholipid syndrome, increased platelet activation, elevated homocysteinemia, elevated plasma factor VII activity, lupus anticoagulant, activated protein C resistance, protein C deficiency, and acquired protein S deficiency. Aims & Objectives: To report our experience with 12 HIV-seropositive subjects with laboratory-confirmed evidence of protein S deficiency, with and without venous or arterial thrombosis, and discuss the diagnostic approach to hypercoagulability in HIV infection, and the clinical management of thromboembolic complications in patients with protein S deficiency. Methods/Study Design: A retrospective review of the medical records of 12 HIV-seropositive patients diagnosed with protein C and S deficiencies at the Lawnwood Regional Medical Center and Heart Institute, Fort Pierce, Florida, from July 2005 through December 2005. All patients were seen by one of the authors (DO), an infectious diseases consultant. Lawnwood Regional Medical Center is a 341-bed, acute care institution and regional referral center for four counties of Treasure Coast, FL, USA. Results/Findings: Seven subjects had symptomatic thromboembolic manifestations that included deep venous thrombosis (5 subjects), pulmonary embolism (4 subjects), inferior vena cava thrombosis (2 subject), and/or stroke (1 subject). An additional five patients were identified with asymptomatic protein S deficiency. All subjects were African-American. Mean patient age was 44 years (range, 21 to 60 years), and the male:female ratio was 5:7. The mean CD4+ cell count was 102 per mm3 (range 0-343), and the mean HIV RNA level was 71,772 copies/mL (range 1,421-554,237 copies/mL). Only three patients were receiving highly active antiretroviral therapy (HAART) at the time of clinical presentation. All symptomatic subjects received heparin, with or without warfarin, for their thromboembolic event and all but one recovered. Conclusion: HIV-infected patients should be screened for acquired protein S deficiency, which contributes to hypercoagulability and risk of clinical thromboembolic events. Asymptomatic patients with reduced plasma free protein S levels may benefit from aspirin primary prophylaxis.