Antiphospholipid Syndrome and Lupus Anticoagulant: Where do we stand today ?

Abstract

Lupus Anticoagulant (LAC) is a group of auto antiantibodies that interfere with phospholipid dependent tests like Activated Partial Thromboplastin time (APTT) and dilute Russell Viper venom time (dRVVT) on in vitro basis. LA, anti cardiolipin antibodies (aCL) IgG/IgM, and anti-β2 glycoprotein I antibodies [aβ2GPI]IgG/IgM are three diagnostic criteria for laboratory diagnosis of anti-phospholipid antibodies (aPL). The circulating aPLs in the clinical setting of hypercoagulability state or adverse pregnancy outcomes is termed as anti-phospholipid syndrome (APS). The laboratory diagnosis of APS is complicated, it includes constellation of tests like solid phase immunoassays for measurement of aCL and a β 2GPI by and coagulation based assays for detection of LAC. LAC diagnosis is especially challenging in the setting of anti-coagulation therapy, numerous modifications to circumvent this interference have rendered success. The Thrombin generation assays [TGA] for LAC detection and estimation of LAC pathogenicity are available but are yet to be accepted as routine laboratory tests. The medley of assays like Enzyme-linked immunosorbent and chemiluminescent assays are available for detection of aCL and aβ2GPI but due to the non-availability of universal calibrators and standards there is lack of harmonization between various solid phase assays. In this article we intend to highlight new recommendations of laboratory diagnosis of LAC with special emphasis on diagnosis in the setting of pregnancy and anti-coagulation. For risk assessment in APS other non-criteria aPL like as anti-domain β2 glycoprotein I and anti-phosphatidyl serine/prothrombin antibodies are under evaluation. There is an ongoing quest towards harmonization of detection of LAC, thus there has been succession of guidelines to meet the challenges and incorporate newly found knowledge every time, namely International Society for Thrombosis and Hematology- Scientific Standardization Committee (ISTH-SSC) guidelines, followed by British Committee for Standards in Hematology (BCSH), Clinical and Laboratory Standards Institute (CLSI) guidelines 2014 and finally guidelines/updates issued by ISTH- SSC in 2018.

Keywords

• lac
• autoantibodies
• immunity
• immunoglobulins
• antibodies