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Antiphospholipid Antibodies

Test code(s) 4661, 4662, 4663, 7352, 30340, 36333, 36552, 36553, 36554, 36595, 91244, 10062, 10163

Question 1. What is antiphospholipid syndrome (APS)?

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

Question 2. Do the cardiolipin and β2GPI assay cut-offs reflect the 99th percentiles of a normal population?

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

Question 3. What do the cardiolipin and β2-glycoprotein I assays detect, and how are results reported?

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. 

Question 4. Why is it recommended to confirm positive results after 12 weeks? 

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

Question 5. Do high positive cardiolipin IgG (eg. >80 GPL-U/mL) antibody levels always correlate with a positive lupus anticoagulant test result?

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

Question 6. Are test results affected if a patient is taking an anticoagulant such as a vitamin K antagonist (eg, warfarin), heparin (low molecular weight and unfractionated heparins), direct thrombin inhibitor (eg, dabigatran), or anti-Xa medication (eg, rivaroxaban, apixaban, and edoxaban)?

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

Question 7. My patient has just had a massive thrombosis. Does this affect cardiolipin or β2GPI antibody results?

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 repeated ³ ≥12 weeks after the event to demonstrate antibody persistence.1

Question 8. What does it mean when only the cardiolipin or β2GPI IgA isotype is positive?

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

Question 9. What is the significance of a positive phosphatidylserine antibody result?

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

Question 10. How can APS affect pregnancy?

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

References

  1. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306. doi:10.1111/j.1538-7836.2006.01753.x
  2. Arslan E, Branch DW. Antiphospholipid syndrome: diagnosis and management in the obstetric patient. Best Pract Res Clin Obstet Gynaecol2020;64:31-40. doi:10.1016/j.bpobgyn.2019.10.001
  3. BioPlex 2200 system APLS IgG. Package insert. BioRad Laboratories Inc;, February 2019.
  4. BioPlex 2200 system APLS IgA. Package insert. BioRad Laboratories Inc; February 2019.
  5. BioPlex 2200 system APLS IgM. Package insert. BioRad Laboratories Inc; February 2019.
  6. Galli M. Interpretation and recommended testing for antiphospholipid antibodies. Semin Thromb Hemost. 2012;38(04):348-352.doi:10.1055/s-0032-1304716
  7. Adcock DM, Gosselin R, Kitchen S, et al. The effect of dabigatran on select specialty coagulation assays. Am J Clin Pathol. 2013;139(1):102–109. doi:10.1309/AJCPY6G6ZITVKPVH
  8. Gosselin R, Grant RP, Adcock DM. Comparison of the effect of the anti-Xa direct oral anticoagulants    apixaban, edoxaban, and rivaroxaban on coagulation assays. Int J Lab Hematol. 2016;38(5):505–513. doi:10.1111/ijlh.12528
  9. Kahles T, Humpich M, Steinmetz H, et al. Phosphatidylserine IgG and beta-2-glycoprotein I IgA antibodies may be a risk factor of ischaemic stroke. Rheumatology (Oxford). 2005;44(9):1161-1165. doi:10.1093/rheumatology/keh698
  10. Ulcova-Gallova Z, Krauz V, Novakova P, et al. Anti-phospholipid antibodies against phosphatidylinositol, and phosphatidylserine are more significant in reproductive failure than antibodies against cardiolipin only. Am J Reprod Immunol. 2005;54(2):112-117. doi:10.1111/j.1600-0897.2005.00294.x
This FAQ is provided for informational purposes only and is not intended as medical advice. A clinician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.
Document FAQS.109 Version: 2
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Version 1 effective 04/09/2016 to 06/24/2021
Version 0 effective 11/04/2013 to 04/08/2016