Unusual Thromboses Associated with Protein S Deficiency in Patients with Acquired Immunodeficiency Syndrome: Case Reports and Review of the Literature

Abstract

Recent reports indicate that patients infected with HIV are at increased risk for the development of thrombosis. Among other possibilities, an acquired deficiency of protein S (PS), one of the plasma's natural anticoagulants, might explain this tendency. PS deficiency can be classified in three types depending on the levels of total and free protein (antigenic assays) as well as anticoagulant activity (functional assay). Although the prevalence of inherited PS deficiency is not known because of its rarity, several conditions can lead to acquired forms of the disease. We report two AIDS patients with coexistent type III PS deficiency and thrombosis. Our first patient presented with bilateral chronic leg ulcers and a skin biopsy revealed dermal microthromboses. On laboratory evaluation he had PS deficiency and was started on anticoagulation, but was lost to follow-up. The second patient presented with hepatic vein thrombosis (Budd-Chiari syndrome) and was also PS deficient. On long-term anticoagulation, she experienced resolution of the thrombosis. Neither patient had prior personal or family history of venous thrombosis, nor acquired risk factors such as immobility, acute infection, recent surgery, or hormonal therapy. The literature contains a few reports of skin ulcers and Budd-Chiari syndrome associated with PS deficiency, although none in AIDS patients. While a larger number of studies describe an association between PS deficiency and HIV infection, the causal effect of this deficiency on the thrombophilic tendency in AIDS has not been established. We propose that awareness of the increased risk for thrombosis in HIV infection is important to the understanding of disease pathophysiology and management of these patients.

Factor VIII concentration is greater in female than male patients with HIV infection

“…In the past few years, many reports have documented an increased risk of venous and arterial thrombosis in HIVinfected patients [10][11][12]. Our observations during clinical practice indicate that female patients with HIV infection are more prone to venous and arterial thrombosis than male patients.…”

HIV positivity, protease inhibitor exposure and subclinical atherosclerosis: a systematic review and meta-analysis of observational studies

“…Heterogeneity was assessed by the I2 statistic. The I2 statistic provides an estimate of the amount of variance due to heterogeneity rather than chance and is based on the traditional measure of variance, the Cochrane Q statistic.…”

“…Inflammation is increasingly accepted as having an important role in the pathogenesis of atherosclerosis and acute cardiovascular events 1. Second, metabolic derangements resulting from HIV may result in dyslipidaemia (especially low high-density lipoprotein (HDL)), endothelial dysfunction, hypercoagulability, platelet activation and impaired fibrinolysis 2 3. Patients with HIV have been described as having histologically unique features of coronary artery disease, including a rapid progression of diffuse, circumferential arterial lesions with proliferation of smooth muscle cells, elastic fibres and endoluminal protrusions 4.…”

Serum concentrations of antiphospholipid and anticardiolipin antibodies are higher in HIV-infected women

“…In the past few years, an increased risk of venous and arterial thrombosis in HIV-infected patients has been documented [10][11][12]. This is partly correlated with an increased serum level of antiphospholipid and anticardiolipin antibodies in these patients [13][14][15][16][17].…”