Antiphospholipid Antibody Syndrome and Pregnancy Workup

  • Author: Teresa G Berg, MD, FACOG; Chief Editor: Carl V Smith, MD   more...
 
Updated: Jan 14, 2011
 

Laboratory Studies

Antiphospholipid syndrome (APS) is diagnosed when the patient has lupus anticoagulant (LAC), IgG or IgM anticardiolipin (aCL) in medium-to-high levels, or anti-beta 2 glycoprotein I (anti-b2GPI) IgG or IgM in titer greater than the 99th percentile on 2 occasions at least 12 weeks apart.

Antiphospholipid (aPL) antibodies are detected by conventional and specific solid-phase or enzyme-linked immunoassays. Results are measured as GPL (IgG aCL), MPL (IgM aCL), or aPL (IgA aCL) units and reported in semiquantitative terms such as negative, low-positive, medium-positive, or high-positive.

Isolated IgA aCL results are also of uncertain clinical significance and are not diagnostic of APS. An easy and reliable test would significantly help detection and follow-up of affected patients.

Autoantibodies include antinuclear antibodies (ANAs), aCL antibodies, anti-DNA antibodies (single-stranded or double-stranded), and anti-b2GPI.

SLE is associated with lower serum complement levels measured either as total hemolytic complement activity CH50 or as levels of the third and fourth components of complement C3 and C4, respectively. Decreased levels of these are indicative of consumption by immune complexes. However, preeclampsia is associated with an increased serum complement level.

Obstetric indications are as follows:

  • Unexplained fetal death or stillbirth
  • Recurrent pregnancy loss (3 or more spontaneous abortions with no more than 1 live birth)
  • Unexplained second or third trimester fetal death
  • Severe preeclampsia at less than 34 weeks’ gestation
  • Unexplained severe fetal growth restriction
  • Chorea gravidarum

Nonobstetric indications are as follows:

  • Nontraumatic thrombosis or thromboembolism (venous or arterial)
  • Stroke, especially in individuals aged 24-50 years
  • Unexplained transient ischemic attack
  • Unexplained amaurosis fugax
  • Autoimmune thrombocytopenia
  • Autoimmune hemolytic anemia
  • Unexplained prolongation of a clotting assay
  • Transient ischemic attacks
  • Livedo reticularis
  • SLE or other connective tissue disorder
  • False-positive serologic test result for syphilis

Laboratory criteria for the diagnosis of APS are as follows:

  • LAC is detected by PL-dependent clotting assays, without correction with normal plasma. Results are confirmed by demonstrating PL dependency. The activated partial thromboplastin time (aPTT) is prolonged. Sera are screened for anticoagulant activity by mixing them with platelet-pool normal sera and assaying the aPTT. Several laboratory measurements are available for the assessment of LAC.
  • For aCL or anti-b2GPI antibodies, an IgG isotype greater than 12-20 GPL units (medium- to high-positive) detected in a standardized assay using standard serum calibrators is indicative.
  • Anti-b2GPI IgG or IgM isotype in serum or plasma greater than the 99th percentile for a normal population as defined by the laboratory performing the test.

Hematologic and serologic values of APS are as follows:

Lupus anticoagulant

Prolonged clotting times with any of the following:

  • aPTT
  • Kaolin clotting time
  • Dilute Russell viper venom time
  • Plasma clotting time

These prolongations should be confirmed with one of the following:

  • Mixing studies with normal plasma, clotting time will remain prolonged with LA
  • Platelet neutralization test (recommended by some authorities

Anticardiolipin antibodies: Many aCL antibodies correlate poorly with the clinical manifestations of APS. At present, only IgG and IgM in moderate and high levels are recommended to be used in the diagnosis of APS.

False-positive results from the VDRL test may be present.

All studies need to be repeated in at least 12 weeks for confirmation before the diagnosis of APS is appropriate.

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Imaging Studies

Appropriate neurologic or imaging studies should be performed based on clinical findings (ie, in the presence of CNS symptoms, a CT scan or MRI).

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Histologic Findings

Histologically, 6 classes of lupus glomerulonephritis have been recognized by the World Health Organization.

  • Class I - Normal glomeruli observed with light microscopy; may show deposits with immunofluorescence or electron microscopy
  • Class II - Mesangial lesions
  • Class III - Focal proliferative glomerulonephritis
  • Class IV - Diffuse proliferative glomerulonephritis
  • Class V - Membranous glomerulonephritis
  • Class VI - Diffuse glomerular sclerosis

Human aCL antibodies cause placental necrosis in BALB/c mice.

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Contributor Information and Disclosures
Author

Teresa G Berg, MD, FACOG  Associate Professor, Program Director, Director of the Perinatal Diagnostic Center, Department of Obstetrics and Gynecology, University of Nebraska Medical Center

Teresa G Berg, MD, FACOG is a member of the following medical societies: American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Bruce A Meyer, MD, MBA  Executive Vice President for Health System Affairs, Chief Clinical Officer, Interim CEO, University Hospitals; Professor, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical School

Bruce A Meyer, MD, MBA is a member of the following medical societies: American College of Obstetricians and Gynecologists, American College of Physician Executives, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Massachusetts Medical Society, Medical Group Management Association, and Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Frederick B Gaupp, MD  Consulting Staff, Department of Family Practice, Hancock Medical Center

Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians

Disclosure: Nothing to disclose.

Chief Editor

Carl V Smith, MD  The Distinguished Chris J and Marie A Olson Chair of Obstetrics and Gynecology, Professor, Department of Obstetrics and Gynecology, University of Nebraska Medical Center

Carl V Smith, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Council of University Chairs of Obstetrics and Gynecology, Nebraska Medical Association, and Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

References

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Table. Proposed Management for Women With aPL Antibodies
FeatureManagement
PregnantNonpregnant
APS with prior fetal death or recurrent pregnancy lossHeparin in prophylactic doses (15,000-20,000 U of unfractionated heparin or equivalent per d) administered subcutaneously in divided doses with low-dose aspirin daily



Calcium and vitamin D supplementation



Optimal management uncertain; options include no treatment or daily treatment with low-dose aspirin
APS with prior thrombosis or strokeHeparin to achieve full anticoagulation (does not cross the placenta)Warfarin administered daily in doses to maintain international normalized ratio of ≥ 3
APS without prior pregnancy loss or thrombosisNo treatment, or daily treatment with low-dose aspirin, or daily treatment with prophylactic doses of heparin plus low-dose aspirin; optimal management uncertain No treatment, or daily treatment with low-dose aspirin; optimal management uncertain
LGBSSHigh-dose IVIG at 400-1500 mg/kg/d for several daysIVIG at 400-1500 mg/kg/d for several days
aPL Antibodies Without APS
LAC or medium-to-high level of aCL IgGNo treatmentNo treatment
Low levels of aCL IgG, only aCL IgM, or only aCL IgA without LA, aPL, or aCLNo treatmentNo treatment
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