What are considerations for antiphospholipid (APL) antibodies testing?

Updated: Jul 22, 2021
  • Author: Tarek Hammad, MD; Chief Editor: Eric B Staros, MD  more...
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It is recommended that patients suspected of having APS undergo testing for all 3 antibodies (LAC, ACL, anti-β2 -GPI), although the presence of only one type of these antibodies is sufficient for diagnosis. Nonetheless, patients who are positive for all 3 antibodies have the highest rate of APS-related complications. [13] If only one test is to be chosen, LAC is the assay of choice since it has the strongest correlation with APS manifestation.

To meet the diagnostic criteria for APS, the test results should be positive on two occasions, 12 weeks apart. This is so that persistent pathologic APL antibodies can be differentiated from transient nonpathologic APL antibodies.

Local cutoff values are calculated by performing the test on at least 40 young (< 50 years) healthy donors.

Tests should be performed when the patient is clinically stable, not during an acute thromboembolic event, for 2 reasons: first, an acute event may trigger the production of transient anticardiolipin antibodies; second, acute events increase the acute-phase reactants such as fibrinogen and factor VIII, which can alter the results of coagulation tests. [14]

LAC detection tests should be performed before anticoagulation therapy is started or after it has been stopped for a sufficient period. Anticardiolipin or anti-β2-glycoprotein I antibody testing is generally not affected by anticoagulation therapy.

The concentration of phospholipids affects the LAC detection results. Phospholipids can react with the APL antibodies in the screening tests (step 1; see Lupus anticoagulant) and prevent prolongation of the these tests, and, since platelets are phospholipid-rich, platelet-free plasma is used in these tests to avoid false-negative results, whereas excess phospholipids are added in step 3 (see Lupus anticoagulant) to confirm that the inhibitor is phospholipid-dependent.

These assays differ in their sensitivity and specificity, and their intralaboratory variability remains high. Efforts to standardize these tests are in process.

People with past or current syphilis may have false positive results without being at risk for thrombosis, as is the case with other infection-, medication-, or neoplasm-induced transient antibodies.

A study by Efthymiou et al of laboratories contributing to the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) registry found that in 28.7% of samples, lupus anticoagulant (LAC) results were equivocal or were discordant between core and local/hospital laboratories. The study suggested that unreliable results may have been obtained from the local/hospital laboratories in 24.7% and 23% of non-anticoagulated and anticoagulated samples, respectively. They cautioned, however, that the differences may also have partially stemmed from equivocal core laboratory results. The investigators stated that in LAC analysis, good agreement between laboratories can be attained through employment of the same reagents, analyzer type, and protocols. [15]

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