Recent advances in understanding antiphospholipid syndrome

Abstract

Antiphospholipid syndrome (APS), also known as Hughes Syndrome, is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. A patient with APS must meet at least one of two clinical criteria (vascular thrombosis or complications of pregnancy) and at least one of two laboratory criteria including the persistent presence of lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and/or anti-b2 glycoprotein I (anti-b2GPI) antibodies of IgG or IgM isotype at medium to high titres in patient’s plasma. However, several other autoantibodies targeting other coagulation cascade proteins (i.e. prothrombin) or their complex with phospholipids (i.e. phosphatidylserine/prothrombin complex), or to some domains of β2GPI, have been proposed to be also relevant to APS. In fact, the value of testing for new aPL specificities in the identification of APS in thrombosis and/or pregnancy morbidity patients is currently being investigated.

Antiphosphatidylserine/prothrombin complex antibodies as a determinant of prothrombotic plasma fibrin clot properties in patients with antiphospholipid syndrome

“…Mechanisms underlying the procoagulant properties of aPS/PT antibodies are poorly explored. It has been postulated that an indirect effect of aPS/PT antibodies on clotting factors, that is, prothrombin or a direct effect on cell receptors, might be involved in the pathogenesis of thrombotic events in APS patients . Oku et al have shown that overexpression of tissue factor in mononuclear cells was induced by both IgG fractions from APS patients positive for aPS/PT and monoclonal aPS/PT antibody, probably through the activation of the p38 mitogen‐activated protein kinase pathway.…”

“…28 Mullen et al 29 the pathogenesis of thrombotic events in APS patients. 30 Oku et al 31 have shown that overexpression of tissue factor in mononuclear cells was induced by both IgG fractions from APS patients positive for aPS/PT and monoclonal aPS/PT antibody, probably through the activation of the p38 mitogen-activated protein kinase pathway.…”

Successful management of concurrent acquired hemophilia A and a lupus anticoagulant in a pediatric hematopoietic stem cell transplant patient

“…Management options for bleeding patients include factor replacement to overcome low-titer inhibitors (<5 Bethesda units/mL, BU/mL), bypassing agents for high-titer inhibitor, and immunosuppression for inhibitor eradication [2]. Lupus anticoagulants (LACs) are pro-thrombotic autoantibodies that interfere with phospholipid and protein interactions [4]. Anti-prothrombin antiphospholipid antibodies are rare, but are associated with bleeding [4].…”

“…Lupus anticoagulants (LACs) are pro-thrombotic autoantibodies that interfere with phospholipid and protein interactions [4]. Anti-prothrombin antiphospholipid antibodies are rare, but are associated with bleeding [4]. LACs are common in autoimmune disorders [4].…”

“…Anti-prothrombin antiphospholipid antibodies are rare, but are associated with bleeding [4]. LACs are common in autoimmune disorders [4]. However, development of both AHA and LAC after allogeneic hematopoietic stem cell transplant (HSCT) in a pediatric setting has not been reported.…”