Antiphospholipid Syndrome Workup

  • Author: Elise Belilos, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Jan 19, 2012
 

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 LA in plasma on 2 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 2 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 2 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.

Recent literature suggests that an abnormal LA finding is the laboratory test result that confers the strongest risk for thrombosis.[8] 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.

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.[9] )
  • 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 include the following:

  • IgA aCL
  • IgA beta-2 glycoprotein I
  • anti-phosphatidylserine antibodies
  • anti-phosphatidylethanolamine antibodies
  • anti-prothrombin antibodies
  • antibodies against the phosphatidylserine-prothrombin complex
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Imaging Studies

  • Imaging studies are helpful for confirming a thrombotic event. A good example is the use of CT scanning or MRI of the brain (CVA), chest (PE), or abdomen (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.
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Procedures

  • Individualize appropriate procedures to evaluate specific thrombotic events.
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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.

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Contributor Information and Disclosures
Author

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, State University of New York at Stony Brook

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

Disclosure: Nothing to disclose.

Coauthor(s)

Steven Carsons, MD  Chief, Division of Rheumatology, Allergy, and Immunology, Professor of Medicine, Department of Internal Medicine, Winthrop University Hospital, State University of New York at Stony Brook

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

Disclosure: Nothing to disclose.

Specialty Editor Board

Carlos J Lozada, MD  Director of Rheumatology Fellowship Program, Professor, 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 and American College of Rheumatology

Disclosure: Pfizer Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching

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

Disclosure: Medscape Salary Employment

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, and American College of Rheumatology

Disclosure: Abbott Honoraria Speaking and teaching; Centocor Consulting fee Consulting; Genentech Grant/research funds Other; HGS/GSK Honoraria Speaking and teaching; Omnicare Consulting fee Consulting; Pfizer Honoraria Speaking and teaching; Roche Speaking and teaching; Savient Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; 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, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

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

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