AnxA5 is a protein that can form a shield over phospholipids to block their availability for critical coagulation enzyme reactions. Previous studies have demonstrated that aPL antibodies can disrupt this anticoagulant shield and unmask anionic phospholipids, leading to thrombosis and pregnancy loss.40,41 The laboratory at Montefiore Medical Center in the Bronx, New York has developed a novel functional assay that measures the aPL antibody–mediated disruption of the AnxA5 shield. In particular, the assay measures the effect of patient plasma on the anticoagulant activity of AnxA5, adding plasma to a phospholipid suspension and then measuring the prolongation of coagulation time by AnxA5.42 The utility of this assay appears primarily in defining a subgroup of patients with clinical manifestations of APS in whom this disease mechanism occurs. The task force recognized that this assay is the first mechanistic assay developed to measure aPL antibodies but felt that additional data are needed before recommending AnxA5 resistance test as a standard component of aPL antibody testing panels.
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The field of aPL antibody testing has evolved tremendously since the first aCL test was described by Harris and colleagues in 1983.43 Controversies and uncertainties still exist despite the significant efforts to standardize the aPL antibody tests. However, the scientific community is aware of these difficulties, and important initiatives are underway to hopefully enhance the performance of tests that are critical for the diagnosis of APS. Even with major laboratory research, the most important question a clinician faces today has remained almost the same since the discovery of aCL: What test(s) should I order to diagnose APS in a patient with thrombosis and/or pregnancy loss?
In the diagnosis and treatment of patients with APS, we believe strongly that clinicians should understand the scientific evidence supporting the use of a particular test and that laboratories should provide interpretative information and consultation to the physicians ordering the test. Such an approach would represent an important advance and hopefully improve the care of patients with these complicated, confusing, and often debilitating conditions.
Drs. Barilaro, Basra, Murthy, Willis, and Pierangel are with the Antiphospholipid Standardization Laboratory, division of rheumatology, department of internal medicine, University of Texas Medical Branch, Galveston, Texas. Dr. Willis is also with the department of microbiology, University of the West Indies, Kingston, Jamaica. Dr. Harris is with the Office of the Vice Chancellor, University of the West Indies. Disclosures: Drs. Pierangeli and Harris are co-owners of Louisville APL Diagnostics, Inc., a company that produces and distributes aPL antibody assays.
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