Antiphospholipid Antibodies

Antiphospholipid syndrome (APS) is a disease state that includes at least 1 clinical event and at least 1 persistently positive antiphospholipid antibody (tested ≥12 weeks apart).¹ The classification criteria for APS are shown in the Table.¹
 

Yes, assay cut-offs were established with receiver operating characteristic (ROC) analysis and comparison against commercially available microplate enzyme immunoassays (EIA) using specimens from patients with APS and healthy blood donors.^3-5 This analysis (performed by the manufacturer) established the assay cutoff at the 99th percentile of a healthy, normal population.^1,3-5

In conjunction with other clinical findings, these tests are used as an aid in the diagnosis of APS and for patients with symptoms of APS that may be secondary to systemic lupus erythematosus (SLE) or SLE-like disorders.^3-5 The assays detect IgG, IgM, and IgA antibodies to cardiolipin and β2-glycoprotein I (β2GPI), respectively, in human citrated plasma and serum. Results for cardiolipin antibodies are expressed in GPL/MPL/APL-U/mL units for IgG, IgM, and IgA antibodies, respectively.^3-5 Results for β2GPI antibodies are expressed in U/mL for IgG, IgA, and IgM. 

The current international consensus statement for the classification criteria of APS suggests confirming positive results after 12 weeks to rule out transient antibodies, which have been described in infectious diseases and are not of clinical significance.¹ For example, antiphospholipid antibodies, such as lupus anticoagulant and low-titer cardiolipin antibodies, may be transient in children with an acute viral illness.¹

Not always, although the correlation is higher with increasing cardiolipin IgG antibody levels. In addition, triple antiphospholipid positivity (ie, positivity for cardiolipin antibody, β2GPI antibody, and lupus anticoagulant) correlates more strongly with both thrombosis and pregnancy morbidity than does single or double positivity.⁶

Anticoagulants do not interfere with results of the cardiolipin and β2GPI antibody testing. In contrast, depending on the level of and type of anticoagulant, lupus anticoagulant testing may or may not be affected.^7,8

A thrombotic event will not likely mask an antiphospholipid antibody, because these antibodies are tested on an immunoassay-based platform. However, a positive antibody titer may be detected for the first time after the thrombotic event; thus, testing should be repeated³ ≥12 weeks after the event to demonstrate antibody persistence.¹

The IgA isotype has been implicated in small studies but has not yet been incorporated into the APS diagnostic criteria.¹ IgA has been reported in African American patients with SLE. It may indicate a subgroup of patients with a nonspecific autoimmune disorder who are at risk for specific clinical manifestations.¹

Phosphatidylserine antibodies have been associated with antibody-mediated thrombotic events, particularly stroke, but have not been incorporated into the classification criteria for the APS. Isolated phosphatidylserine IgM antibodies that are near the cutoff for positivity often reflect an underlying acute-phase response (eg, to an infectious agent) rather than a true positive result.^9,10

Antiphospholipid antibodies can increase risk for thrombosis in pregnant women and have been associated with adverse pregnancy outcomes.² Indeed, clinical criteria that can be used to diagnose APS include several pregnancy-related morbidities, such as unexplained recurrent miscarriage, unexplained fetal death, and severe pre-eclampsia leading to preterm birth.² Importantly, these clinical manifestations can have many underlying causes and should be assessed with accompanying laboratory diagnostics to determine if APS is a potential etiological factor.^1,2