eMedicine Specialties > Obstetrics and Gynecology > Medical Problems in Pregnancy

Antiphospholipid Antibody Syndrome and Pregnancy: Differential Diagnoses & Workup

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
Contributor Information and Disclosures

Updated: Aug 11, 2008

Differential Diagnoses

Preeclampsia
Thymic Tumors

Other Problems to Be Considered

In women meeting the clinical criteria of early pregnancy loss, care must be taken to assure that the evaluation of spontaneous abortions prior to the 10 weeks’ gestation has included the appropriate evaluation to be considered unexplained.

Other causes of thrombocytopenia such as HIV infection, drug-induced thrombocytopenia, thrombotic thrombocytopenia, gestational thrombocytopenia, and preeclampsia should be considered. Other autoimmune disease should be ruled out in patients with thrombocytopenia.

Many manifestations of SLE can be seen in women with APS. A complete evaluation to exclude SLE as a primary disorder is appropriate if symptoms are present.

Workup

Laboratory Studies

  • Antiphospholipid syndrome (APS) is diagnosed when the patient has lupus anticoagulant (LAC) or IgG or IgM anticardiolipin (aCL) in medium-to-high levels, or both, on 2 occasions at least several 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- 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.
  • Indications for testing for aPL antibodies include the following:  
    • Obstetric indications
      • 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 
      • 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.
  • 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 6 weeks for confirmation before the diagnosis of APS is appropriate.

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).

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.

More on Antiphospholipid Antibody Syndrome and Pregnancy

Overview: Antiphospholipid Antibody Syndrome and Pregnancy
Differential Diagnoses & Workup: Antiphospholipid Antibody Syndrome and Pregnancy
Treatment & Medication: Antiphospholipid Antibody Syndrome and Pregnancy
Follow-up: Antiphospholipid Antibody Syndrome and Pregnancy
References
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References

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Further Reading

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Keywords

antiphospholipid syndrome, APS, lupus anticoagulant, LAC, anticardiolipin antibodies, aCL, autoimmune disease, systemic lupus erythematosus, lupus, SLE,  lupus erythematosus, LE, fetal loss, thrombosis, autoimmune thrombocytopenia, infertility, pregnancy complications, fetal mortality, fetal morbidity, maternal morbidity, spontaneous abortion, prematurity, stillbirth, fetal growth restriction, FGR, fetal growth retardation

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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.

Medical Editor

Bruce A Meyer, MD, MBA, Vice President for Medical Affairs, Associate Dean for Health System Affairs and Director of the Faculty Practice Plan, 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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

CME Editor

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, American Medical Association, Arkansas Medical Society, 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.

 
 
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