Antiphospholipid syndrome (APS), also called antiphospholipid antibody syndrome, is an autoimmune disorder in which autoantibodies are directed against phospholipid-protein complexes. APS is characterized by thromboses (arterial, venous, or small vessel) and/or pregnancy complications and persistently positive tests for antiphospholipid-protein (aPL) antibodies. Cytopenias, other hematologic disorders, and neurologic, dermatologic, or cardiopulmonary abnormalities may also be seen in patients with APS. An uncommon acute form of the syndrome, catastrophic APS, results in extensive thrombotic microangiopathy and multiorgan failure. Those at increased risk for APS include patients with systemic lupus erythematosus (SLE), infections, malignancy, and liver or vascular disease. Some medications are also associated with increased risk. Transient aPL antibodies may occur in association with infections, certain medications (procainamide, chlorpromazine), and malignancy.
Quick Answers for Clinicians
Three test groups, used together, are recommended for antiphospholipid syndrome (APS) diagnosis. They include lupus anticoagulant (LA), anticardiolipin (aCL) antibodies (immunoglobulin G [IgG] and IgM), and anti-beta-2 glycoprotein 1 (anti-β2GP1) antibodies (IgG and/or IgM). If one or more of these tests are positive, the test(s) should be repeated at least 12 weeks later to confirm persistent positivity. If the tests are negative but strong suspicion for APS remains, “noncriteria” tests are indicated. See Noncriteria Tests.
Because antiphospholipid-protein (aPL) antibodies can occur transiently, persistent positivity is required for diagnosis of antiphospholipid syndrome (APS). In addition, testing for lupus anticoagulant (LA), anticardiolipin (aCL) antibodies, and anti-beta-2 glycoprotein 1 (anti-β2GP1) antibodies reduces the risk of false-negative findings and helps in assessing risk for complications such as thrombotic events.
Indications for Testing
Testing for APS is appropriate for individuals with indications of APS, such as venous or arterial thromboses or pregnancy-related morbidity (see Quick Answers for Clinicians for complete list of indications).
Criteria for Diagnosis
Laboratory Testing
Diagnosis
First-Line or Criteria Tests
Current recommendations for first-line testing in APS include lupus anticoagulant (LA) clot-based assays and tests for aCL IgG and IgM antibodies and anti-β2GP1 IgG and IgM antibodies (available together in an APS panel test in some labs). The combination of the three tests reduces the risk of false-negative findings and is important for estimating disease risk. Positivity for all three (LA as well as aCL and β2GP1 antibodies) is strongly associated with thromboembolism and pregnancy-related morbidity. Triple positivity also indicates a high risk of thrombotic recurrence in patients with APS.
If positive, laboratory tests should be repeated at least 12 weeks later to confirm persistent positivity.
Lupus Anticoagulant
At least two phospholipid-dependent clotting assays with appropriate reflexive steps to satisfy detection guidelines, based on different principles (such as activated partial thromboplastin time [aPTT] and dilute Russell viper venom testing [dRVVT]), should be performed to identify LA. Positivity for LA alone, apart from the other aPLs, has a strong association with thrombotic events and adverse outcomes in pregnancy.
Anticardiolipin and Anti-Beta-2 Glycoprotein 1 Antibodies
A strong correlation has been observed between aCL and anti-β2GP1 antibody concentrations, but testing for both antibody types in conjunction with LA is still recommended. Detecting aCL and anti-β2GP1 antibodies of the same isotype (IgG or IgM) supports the likelihood of APS. Measurement of both IgG and IgM is advised.
Noncriteria Tests
If tests for the antibodies relevant to APS diagnostic criteria are negative, but there is strong suspicion for APS, “noncriteria” aPL tests may be indicated. These include tests for phosphatidylserine/prothrombin antibodies (IgG and IgM), phosphatidylserine antibodies (IgG and IgM), prothrombin antibody (IgG), anti-β2GP1 antibody (IgA), and aCL antibody (IgA).
ARUP Laboratory Tests
Electromagnetic Mechanical Clot Detection/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Electromagnetic Mechanical Clot Detection
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Components: phosphatidylserine antibody, IgG and IgM; phosphatidylserine and prothrombin antibody, IgG and IgM; and prothrombin antibody, IgG
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Related Tests
Electromagnetic Mechanical Clot Detection
Qualitative Clotting
Chromogenic Assay/Electromagnetic Mechanical Clot Detection/Quantitative Enzymatic Assay/Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Polymerase Chain Reaction/Fluorescence Monitoring/Microlatex Particle-Mediated Immunoassay
References
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Bertolaccini ML, Amengual O, Andreoli L, et al. 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev. 2014;13(9):917-930.
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Devreese KMJ, Ortel TL, Pengo V, et al. Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH. J Thromb Haemost. 2018;16(4):809-813.
CLSI - Laboratory Testing for the Lupus Anticoagulant; Approved Guideline. CLSI document H60-A
Clinical and Laboratory Standards Institute. Laboratory testing for the lupus anticoagulant; approved guideline. CLSI document H60-A. [Reaffirmed: Sep 2019; Accessed: Sep 2020]
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Legault K, Schunemann H, Hillis C, et al. McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome. J Thromb Haemost. 2018. [Published online ahead of print Jun 2018]
Medical Experts
Moser

Nandakumar

Rodgers III

Smock

Components: anti-β2GP1 antibodies, IgG and IgM; aCL antibodies, IgG and IgM; and LA reflexive panel