Pathogenesis, Diagnosis and Management of Obstetric Antiphospholipid Syndrome: A Comprehensive Review

Abstract

Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity associated with persistent antiphospholipid antibody positivity. Cases fulfilling the Sydney criteria for obstetric morbidity with no previous thrombosis are known as obstetric antiphospholipid syndrome (OAPS). OAPS is the most identified cause of recurrent pregnancy loss and late-pregnancy morbidity related to placental injury. Cases with incomplete clinical or laboratory data are classified as obstetric morbidity APS (OMAPS) and non-criteria OAPS (NC-OAPS), respectively. Inflammatory and thrombotic mechanisms are involved in the pathophysiology of OAPS. Trophoblasts, endothelium, platelets and innate immune cells are key cellular players. Complement activation plays a crucial pathogenic role. Secondary placental thrombosis appears by clot formation in response to tissue factor activation. New risk assessment tools could improve the prediction of obstetric complication recurrences or thromboses. The standard-of-care treatment consists of low-dose aspirin and prophylactic low molecular weight heparin. In refractory cases, the addition of hydroxychloroquine, low-dose prednisone or IVIG improve pregnancy outcomes. Statins and eculizumab are currently being tested for treating selected OAPS women. Finally, we revisited recent insights and concerns about the pathophysiology, diagnosis and management of OAPS.

Circulating immune-complexes of IgG/IgM bound to B2-glycoprotein-I associated with complement consumption and thrombocytopenia in antiphospholipid syndrome

“…This finding is in agreement with the known fact that the IgM isotype is important in obstetric APS: isolated IgM aPL are frequent in obstetric APS and rare in thrombotic APS ( 39 ). This reinforces the idea that obstetric and thrombotic APS most likely have a different pathogenesis despite sharing the same antigenic specificity of the antibodies ( 40 ).…”

Genetic variation in toll-like receptor 4 gene with primary antiphospholipid syndrome susceptibility: a cohort of Egyptian patients

“…APS can be diagnosed by detecting aCL and anti-β2GPI antibodies or using LA coagulation test [20][21][22]. APS is commonly associated with obstetric events, such as complications of pregnancy, and vascular or thrombotic events including venous and arterial thrombosis [6,23].…”

“…APS may arise in isolation without underlying disease in more than 50% of patients, a condition known as PAPS [6]. However, there is a lack of population-based studies assessing the prevalence and incidence of APS, with the estimated incidence in previous studies ranging between 40 and 50 cases per 100,000 in the general population [4].…”

Relationship Between Gender Differences and Clinical Outcome in Patients With the Antiphospholipid Syndrome

“…These can be detected by the identification of anti-cardiolipin (aCL) and anti-b2-glycoprotein I (ab2-GPI) antibodies and by the Lupus Anticoagulant (LA) coagulation test (1)(2)(3)(4). The main clinical variants of the syndrome are two: obstetric APS, characterized by pregnancy morbidity, and vascular or thrombotic APS, characterized by the occurrence of venous and arterial thrombosis (5,6). Other additional symptoms may include thrombocytopenia, nephropathy, cutaneous manifestations (livedo reticularis) and central nervous system symptoms, such as cognitive abnormalities and epilepsy (7,8).…”