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Antiphospholipid Syndrome Workup

  • Author: Suneel Movva, MD; Chief Editor: Herbert S Diamond, MD  more...
Updated: Jul 01, 2016

Laboratory Studies

The hallmark result from laboratory tests that defines antiphospholipid syndrome (APS) is the presence of antiphospholipid (aPL) antibodies or abnormalities in phospholipid-dependent tests of coagulation. In addition to the clinical criteria listed in History, at least one of the following laboratory criteria is necessary for the classification of APS:

  • Presence of lupus anticoagulant (LA) in plasma on two or more occasions at least 12 weeks apart (see below)
  • Presence of moderate to high levels of anticardiolipin (aCL) (IgG or IgM) in serum or plasma (ie, >40 IgG phospholipid units (GPL)/mL or IgM phospholipid units (MPL)/mL or >99th percentile) on two or more occasions at least 12 weeks apart
  • Presence of moderate to high levels of anti–beta-2 glycoprotein I antibodies (IgG or IgM) in serum or plasma (>99th percentile) on two or more occasions at least 12 weeks apart

aCL antibodies react primarily to membrane phospholipids, such as cardiolipin and phosphatidylserine. Of the 3 known isotypes of aCL (ie, IgG, IgM, immunoglobulin A [IgA]), IgG correlates most strongly with thrombotic events. Cardiolipin is the dominant antigen used in most serologic tests for syphilis; consequently, these patients may have a false-positive test result for syphilis.

The literature suggests that an abnormal LA finding is the laboratory test result that confers the strongest risk for thrombosis.[5, 12] LA is directed against plasma coagulation molecules. In vitro, this interaction results in the paradoxical prolongation of clotting assays, such as activated partial thromboplastin time (aPTT), kaolin clotting time, and dilute Russell viper venom time (DRVVT). The presence of LA is confirmed by mixing normal platelet-poor plasma with the patient's plasma. If a clotting factor is deficient, the addition of normal plasma corrects the prolonged clotting time. If the clotting time does not normalize during mixing studies, an inhibitor is present; the absence of a specific clotting factor inhibitor confirms that a LA is present.

Currently, there is much investigation into risk-stratifying patients based on aPL profile, aPL titers, associated autoimmune disease, and other cardiovascular risk factors. "Triple-positive" patients (LA, anti-beta-2 glycoprotein antibodies, AC antibodies) are at highest risk for thrombosis or abnormal pregnancy, and possibly for recurrence.[5] Standardized scoring systems such as the Global Antiphospholipid Syndrome Score (GAPSS) are being developed.

Patients with APS may have one or more abnormal results from these laboratory tests; the following laboratory tests should be considered in a patient suspected of having APS:

  • aCL antibodies (IgG, IgM)
  • Anti–beta-2 glycoprotein I antibodies (IgG, IgM)
  • Activated partial thromboplastin time (aPTT)
  • LA tests such as DRVVT (A threshold of approximately 1.6 for the DRVVT ratio has been recommended for helping discriminate APS from non-APS. [13] )
  • Serologic test for syphilis (false-positive result)
  • CBC count (thrombocytopenia, hemolytic anemia)

Thrombocytopenia is fairly common in persons with APS (22% at presentation, 30% cumulatively) and is therefore associated with paradoxical thrombosis. However, patients with platelet counts of less than 50,000/µL may have an increased risk of bleeding. Hemolytic anemia has been well described in patients with APS and is associated with the presence of IgM aCL antibodies.

A low antinuclear antibody level may be present and does not necessarily imply coexisting SLE.

Additional antibodies directed against phospholipid/phospholipid-protein complexes that may be useful in selected cases (seronegative APS because they are not part of the 2006 consensus criteria) include the following[14, 15, 8] :

  • IgA aCL
  • IgA beta-2 glycoprotein I
  • Anti-phosphatidylserine antibodies
  • Anti-phosphatidylethanolamine antibodies
  • Anti-prothrombin antibodies
  • Antibodies against the phosphatidylserine-prothrombin complex

Imaging Studies

Imaging studies are helpful for confirming a thrombotic event. Examples are the use of computed tomography (CT) or magnetic resonance imaging (MRI) scans of the following:

  • Brain (for stroke)
  • Chest (for pulmonary embolism)
  • Abdomen (for Budd-Chiari syndrome)

Doppler ultrasound studies are recommended for possible detection of DVT.

Two-dimensional echocardiography findings may demonstrate asymptomatic valve thickening, vegetations, or valvular insufficiency; aortic or mitral insufficiency is the most common valvular defect found in persons with Libman-Sacks endocarditis.


Histologic Findings

Unlike inflammatory autoimmune diseases, histologic studies of skin or other involved tissue reveal a noninflammatory bland thrombosis with no signs of perivascular inflammation or leukocytoclastic vasculitis. Similarly, biopsy samples from affected kidneys demonstrate glomerular and small arterial microthrombi.

Contributor Information and Disclosures

Suneel Movva, MD Fellow in Rheumatology, Division of Rheumatology, Allergy and Immunology, Winthrop University Hospital

Disclosure: Nothing to disclose.


Steven Carsons, MD Chief, Division of Rheumatology, Allergy and Immunology, Winthrop University Hospital; Professor of Medicine, Stony Brook University School of Medicine

Steven Carsons, MD is a member of the following medical societies: American College of Rheumatology, New York Academy of Sciences, Society for Experimental Biology and Medicine

Disclosure: Nothing to disclose.

Elise Belilos, MD Section Head of Rheumatology, Division of Rheumatology, Allergy and Immunology, Winthrop University Hospital; Assistant Professor of Clinical Medicine, Department of Internal Medicine, Stony Brook University School of Medicine

Elise Belilos, MD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Janssen<br/>Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Genentech; Pfizer; Questcor.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Carlos J Lozada, MD Director of Rheumatology Fellowship Training Program, Professor of Clinical Medicine, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine

Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Received honoraria from Pfizer for consulting; Received grant/research funds from AbbVie for other; Received honoraria from Heel for consulting.


The authors gratefully acknowledge the contributions of Amiel Tokayer, MD.

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Antiphospholipid syndrome. Livedo reticularis.
Antiphospholipid syndrome. Arterial thrombosis resulting in ischemia and necrosis of the foot.
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