Antiphospholipid Antibody Testing

Excerpt

Antiphospholipid testing is part of the diagnostic workup for possible underlying autoimmune conditions in patients presenting with arterial, venous, and microvascular thrombosis, along with gestational or obstetric complications and morbidity. This testing includes 3 main antibody classifications:

1. Lupus anticoagulants (IgG, IgM)

2. Anticardiolipin antibodies (IgA, IgG, and IgM)

3. Anti-β2-glycoprotein Ib (anti-β2GPIb) antibodies (IgA, IgG, and IgM)

These antibodies should be tested together to assess the risk profile for high-risk patients for antiphospholipid syndrome. Incomplete antiphospholipid diagnostic testing could lead to improper diagnosis of antiphospholipid syndrome and could impose catastrophic consequences without intervention.

Lupus anticoagulant refers to a diverse antibody group directed against phospholipids and phospholipid-binding proteins, which prolong certain coagulation testing in vitro and cause thrombosis in vivo. Lupus anticoagulant detection involves assessing its effect on various anticoagulation tests, and no single assay measures all the different lupus anticoagulant antibodies. Therefore, at least 2 different confirmatory tests are required to establish a positive lupus anticoagulant test. Lupus anticoagulant is considered the most predictive test for thrombosis among antibody tests when positive.

Cardiolipin is an inner mitochondrial membrane component comprising about 20% of the total lipid composition. Anticardiolipin binding to phospholipid anions causes platelet activation. Anticardiolipin antibodies are considered more sensitive but less specific compared to lupus anticoagulants for predicting thrombosis.

Anti-β2GPIb antibodies bind to platelets at the apoER2′ and glycoprotein Ib-α receptors, activating the platelet signaling pathway involving MAPK phosphorylation, GP IIb/IIIa conformational change, P-selectin expression, and thromboxane B2 production.