Antiphosphatidylserine/Prothrombin Complex, IgM

Antiphospholipid antibodies (aPL) are a family of immunoglobulins of considerable clinical significance due to their association with arterial and/or venous thrombosis, recurrent pregnancy loss, neurological disorders, pulmonary hypertension and thrombocytopenia. These antibodies are directed against phospholipid binding proteins or their complex with phospholipid. The best-studied phospholipid-binding proteins include B2 glycoprotein 1 and prothrombin.

Current laboratory assays recommended in the diagnosis of antiphospholipid syndrome (aPS), based on an international consensus guidelines, include anticardiolipin antibodies (aCL), B2 glycoprotein 1 antibodies (aB2Gp1) and detection of a lupus anticoagulant (LA) using clot-based assays. In regard to correlation with clinical manifestations of aPS, lupus anticoagulants are the most important laboratory finding followed by B2Gp1 IgG, then B2Gp1 IgM with isolated aCL, antiprothrombin and antiphosphatidylserine antibodies demonstrating significantly less correlation with aPS clinical manifestations. It has more recently been demonstrated that the antibodies most closely associated with aPS and LA are actually directed to a complex of anionic phospholipids such as phosphatidylserine/prothrombin (PS/PT) rather than to prothrombin alone. Also, thrombosis and pregnancy-related complications are more common in those with positivity in all three assays (LA, aCL and B2GpI of the same isotype) when the ELISA assays at positive at significant titer and this constellation is called triple positivity.

A very high degree of concordance has been demonstrated between the concentration of aPS/PT and lupus anticoagulant (LA) activity, and thus aPS/PT may play a useful role in confirming LA activity in those patients on anticoagulant therapy where LA testing may be spuriously positive due to the anticoagulant interference or when there is difficult LA test interpretation.¹ Furthermore, in APS patients, aPS/PT antibodies have been found to be highly associated with venous thrombosis and obstetric abnormalities.¹

aPS/PT testing may help identify APS in patients with thrombosis or pregnancy loss in whom APS is strongly suspected but conventional antiphospholipid testing is repeatedly negative. In a cohort of patients with SLE, triple positivity for LA, antiB2GP1 and aPS/PT was more strongly associated with thrombosis and/or pregnancy loss (OR 23.2) than any other combination of LA and antiphospholipid antibodies, including triple positivity for LA, anticardiolipin and antiB2Gp1 (OR 14.9).² Inclusion of aPT/PS testing into the standard aPL battery of assays may allow better quantitation of thrombotic risk and risk for pregnancy loss. Antiprothrombin IgG, IgM and antiphosphatidylserine IgG, IgM and IgA assays demonstrate little specificity for the clinical manifestations of aPS.³