The designation 'antiphospholipid syndrome' was proposed for the association of arterial and venous thrombosis, recurrent fetal loss, and immune thrombocytopenia with a spectrum of autoantibodies directed against cellular phospholipid components. Anticardiolipin antibodies may react with cardiolipin and with ... The designation 'antiphospholipid syndrome' was proposed for the association of arterial and venous thrombosis, recurrent fetal loss, and immune thrombocytopenia with a spectrum of autoantibodies directed against cellular phospholipid components. Anticardiolipin antibodies may react with cardiolipin and with other negatively charged phospholipids, including beta-2-glycoprotein I (B2GPI, APOH; 138700). The term 'lupus anticoagulant' refers to a heterogeneous group of antibodies, most commonly of the IgG type, that are detected by their inhibitory effect on coagulant-active phospholipid components of in vitro coagulation tests (summary by Matthey et al., 1989). Shoenfeld et al. (2008) noted that antiphospholipid syndrome is characterized by up to 30 different autoantibodies, including those against platelets, glycoproteins, coagulation factors, lamins, mitochondrial antigens, and cell surface markers. Some of these may have an additive effect on the prothrombotic tendency of the syndrome. Ruiz-Irastorza et al. (2010) reviewed pathophysiologic, clinical, diagnostic, and therapeutic advances related to the antiphospholipid syndrome. Various autoimmune disorders that cluster in families, including autoimmune thrombocytopenia (188030), are discussed elsewhere (e.g., 109100, 269200).
Hellan et al. (1998) described a brother and sister with lupus anticoagulant, elevated anticardiolipin-immunoglobulin G levels, and systemic lupus erythematosus (SLE; 152700) or related autoimmune disorder. Both patients experienced venous thrombotic complications at an early age. The woman ... Hellan et al. (1998) described a brother and sister with lupus anticoagulant, elevated anticardiolipin-immunoglobulin G levels, and systemic lupus erythematosus (SLE; 152700) or related autoimmune disorder. Both patients experienced venous thrombotic complications at an early age. The woman first presented with symptoms of spontaneous deep vein thrombosis of the right leg at the age of 22 years. The brother had been hospitalized at the age of 13 years for symptoms of arthritis of multiple joints and hepatosplenomegaly. He was found to have serologic and histologic evidence for lupus. At the age of 17 years, he presented with deep vein thrombosis of the right leg after a minor trauma. An association between the presence of lupus anticoagulant and the development of abnormalities of the heart valves was suggested by Hoshide et al. (1998), who described typical mitral stenosis in a patient with SLE associated with lupus anticoagulant. Brenner et al. (1996) observed a 23-year-old female and her 19-year-old sister, the offspring of a first-cousin marriage, who presented with unusual recurrent severe thromboembolic phenomenon and were found to have familial antiphospholipid syndrome and also to be heterozygous for the R506Q mutation of factor V (612309.0001). The coexistence of hereditary and acquired APC-resistance was thought to explain the severity of the thromboembolism. The older sib presented with deep vein thrombosis of the proximal left leg and intrauterine fetal death at 20 weeks of gestation in her third pregnancy. During her fourth pregnancy she received enoxaparine from the tenth week of gestation, but intrauterine fetal death occurred at 20 weeks of gestation. Three weeks later she developed right popliteal deep vein thrombosis. The younger sister was admitted to hospital with infarction of lumbar vertebra L4 demonstrated by bone scan, first-trimester abortion, and pancytopenia. Akiguchi et al. (1999) reported a 2-generation family with 3 generations of cousin marriages that was segregating lupus anticoagulant and Binswanger disease. The 60-year-old proband began insidious decline at age 57. Lupus anticoagulant was positive but anticardiolipin antibodies were negative. Multiple lacunes were present in a younger brother, in a younger sister, who also had venous thrombosis, and in 1 daughter, who also had SLE. Gelfand et al. (1999) reported the systemic and ophthalmic involvement in 39 consecutive patients with primary antiphospholipid syndrome. The first 20 consecutive patients underwent retinal fluorescein angiography. The most common forms of systemic involvement included fetal loss (46%), central nervous system involvement (44%), and venous thrombosis (41%). Thirty-three percent of patients had ocular symptoms; these were usually visual disturbances and were most often transient. Pathologic ocular findings directly related to the disease were found in 13% of the patients, and only 5% had intraocular pathology, which consisted of very mild retinopathy. Ocular findings were present in only 6% of the asymptomatic patients. Routine retinal angiography did not reveal any additional information. The authors concluded that ocular involvement in the primary antiphospholipid syndrome is uncommon. Transient visual disturbances are common, although most of them are related to central nervous system rather than ocular ischemia. Miserocchi et al. (2001) evaluated the ophthalmic features in 13 patients presenting with ocular inflammation in the presence of anticardiolipin antibodies. All patients had abnormal titers of anticardiolipin antibodies, predominantly the IgG isotype; 46% had markers of immune activation. Systemic symptoms were frequently present in association with ocular disease. The most common ocular symptom at presentation was blurred vision (62%), followed by pain (23%) and visual loss (15%). Seventy-six percent of patients had anterior segment abnormalities, including iritis (62%), scleritis (15%), and filamentary keratitis (7%). The most common posterior segment feature was retinal vasculitis (60%), followed by vitritis (38%), retinal detachment (15%), scleritis (7%), and central retinal artery occlusion (7%).
Hirose et al. (1999) found that a polymorphism in the APOH gene (V247L) was significantly associated with decreased levels of anti-beta-2-glycoprotein I (B2GPI) antibodies in Asian patients with antiphospholipid syndrome in a study of 370 healthy controls from ... Hirose et al. (1999) found that a polymorphism in the APOH gene (V247L) was significantly associated with decreased levels of anti-beta-2-glycoprotein I (B2GPI) antibodies in Asian patients with antiphospholipid syndrome in a study of 370 healthy controls from different racial backgrounds and 149 patients with APS. The V allele and the VV genotype were found more frequently among Asian patients with antiphospholipid syndrome than among controls (p = 0.0028 and p = 0.0023, respectively). There were no significant differences in allele or genotype frequencies when comparing Caucasian or African American APS patients with appropriate controls. The differences in allele and genotype frequencies seen in Asian APS patients were restricted to those with anti-B2GPI antibodies.