Molecular Pathogenesis of the Antiphospholipid Syndrome

Abstract

Abstract-The antiphospholipid (aPL) syndrome is an acquired autoimmune disorder of unknown etiology in which patients present with thrombosis together with laboratory evidence for antibodies in blood that recognize anionic phospholipid-protein complexes. The main antigenic target for the aPL antibodies has been identified to be ␤ 2 glycoprotein I (␤ 2 GPI), a phospholipid-binding protein. The high affinity of aPL antibody-␤ 2 GPI complex for phospholipid membranes seems to be a critical step in the mechanism of this disease. This review focuses on some of the major mechanisms that have been proposed to explain this disorder. (Circ Res. 2002;90:29-37.)

Inflammatory response and the endothelium

“…[12]), (iv) to displace annexin V binding to the cell membrane [13], (v) to induce pre-pro-endothelin (ET)-I synthesis [14], (vi) to favour an apoptotic process [15,16] and (vii) to interact with late endosomes [17] (Table 1).…”

Avascular necrosis of bone with hemiparesis: a rare presentation of primary antiphospholipid antibody syndrome

“…Table 2, the clinical manifestations of the syndrome include venous and arterial thromboses and embolisms, disseminated large and small vessel thromboses with accompanying multi-organ ischemia and infarction, stroke, premature coronary artery disease, and spontaneous pregnancy losses. 3 The aetiology of APS is multifactorial, and an exact, single cause cannot always be determined. 3,4 Pathophysiology includes the activation of endothelium, oxidized LDL mediated vascular injury, heparin induced thrombocytopenia and molecular mimicry.…”

“…3 The aetiology of APS is multifactorial, and an exact, single cause cannot always be determined. 3,4 Pathophysiology includes the activation of endothelium, oxidized LDL mediated vascular injury, heparin induced thrombocytopenia and molecular mimicry. According to the largest survey of APS patients to date, deep vein thrombosis, sometimes accompanied by pulmonary embolism, is the most frequently reported manifestation of this syndrome (38.9%).…”

Catastrophic Antiphospholipid Syndrome Triggered by Sepsis

“…A "trigger" factor often plays an important role in the development of thrombosis in antiphospholipid antibody (aPL)-positive patients [2]. A cohort analysis of 250 patients in the international web-based CAPS registry [25] identified numerous precipitating factors for CAPS, including infection (22%), trauma (14%), anticoagulation withdrawal (7%), malignancies (7%), obstetric complications (6%), and interestingly, 40% without any identifiable triggers [3].…”