Antiphospholipid Antibody Syndrome and Pregnancy Clinical Presentation

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

History

The “International consensus statement for the diagnosis of antiphospholipid syndrome” was published in 1999 by Wilson et al.[4] This serves as a set of criteria similar to the criteria for the diagnosis of other autoimmune disorders. Diagnosis of antiphospholipid syndrome (APS) requires at least 1 clinical and 1 laboratory criterion.

Clinical criteria

Vascular thrombosis: One or more clinical episodes of arterial, venous, or small-vessel thrombosis, occurring within any tissue or organ

Complications of pregnancy include the following:

  • One or more unexplained deaths of morphologically normal fetuses at or after 10 weeks’ gestation
  • One or more premature births of morphologically normal fetuses at or before 34 weeks’ gestation
  • Three or more unexplained consecutive spontaneous abortions before 10 weeks’ gestation

Laboratory criteria

These criteria for laboratory testing are consistent with current American Congress of Obstetricians and Gynecologists clinical management guidelines.[47]

  • Anticardiolipin antibodies - Anticardiolipin IgG or IgM antibodies present at moderate or high levels in the blood on 2 or more occasions at least 12 weeks apart
  • Lupus anticoagulant - Lupus anticoagulant antibodies detected in the blood on 2 or more occasions at least 12 weeks apart, according to the guidelines of the International Society on Thrombosis and Hemostasis[48]
  • Anti-beta 2 glycoprotein I IgG or IgM greater than the 99th percentile for normal as defined by the laboratory performing the test
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Physical

APS is primarily a diagnosis based on clinical history and laboratory data. Some physical findings may be associated with primary APS, but patients with secondary APS are more likely to have findings on physical examination.

Thrombosis and stroke are possible residual neurologic findings.

Cutaneous manifestations include the following:

  • These may include digital cyanosis, livedo reticularis, digital gangrene, and leg ulcers. The cause of these features remains otherwise unexplained.
  • Other features related to cutaneous manifestations, with a cause that remains unexplained, include transient ischemic attacks or amaurosis fugax, positive result from the Coombs test, hemolytic anemia, chorea, and chorea gravidarum.
  • Discoid rash (ie, erythematous raised patch with keratotic scaling and follicular plugging) is a criterion. Older lesions may be atrophic. Again, the cause remains unexplained.
  • Photosensitivity with an unexplained cause is another criterion.

The following are physical findings that should be considered secondary to other autoimmune disorders and an appropriate evaluation should be undertaken.

  • Arthritis: Patients may have nonerosive arthritis involving 2 or more peripheral joints, and the cause cannot otherwise be determined.
  • Serositis: This may be (1) pleuritis or pleural effusion or (2) pericarditis or pericardial effusion, the cause of which cannot be explained.
  • Renal disorder: Proteinuria of 0.5 g/d or the presence of cellular casts, without another cause, is a criterion for APS.
  • Neurologic disorder: Criteria include seizures in the absence of other causes or psychosis in the absence of other causes.
  • Hematologic disorder: Features, without an otherwise explainable cause, include (1) hemolytic anemia with reticulocytosis, (2) leukopenia of less than 4000 cells/mm3 on at least 2 occasions, (3) lymphopenia of less than 1500 cells/mm3, or (4) thrombocytopenia of less than 100,000 cells/mm3.
  • Immunologic disorder: Again, the cause remains unexplained.

The clinical manifestations of SLE include the following:

  • Skin lesions - 84-71%
  • Arthritis - 63-95%
  • Nephritis - 46-77%
  • Raynaud phenomenon - 10-58%
  • Neuropsychiatric features - 0-59%
  • Lymphadenopathy - 0-58%
  • Pleurisy - 37-56%
  • Mucous membrane ulceration - 7-54%
  • Pericarditis - 29-45%
  • Splenomegaly - 9-18%
  • Aseptic necrosis - 0-10%
  • Clinical evidence of glomerulonephritis is found in more than 50% of cases. However, if biopsies are performed on all patients, the incidence of some nephritis may be as high as 90%. SLE is associated with encephalopathy and seizures, to a lesser degree with ischemic stroke, and, rarely, with subarachnoid hemorrhage.
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Causes

Like other autoimmune disorders, APS does not have a known etiology.

Passive transfer of maternal antibodies mediate autoimmune disorders in the fetus and newborn. The mechanism of excess autoantibody production and immune complex formation is not well understood, although current investigation is focused on abnormal regulator functions and the possibility of a slow virus infection. In addition, certain genetic factors may be important, as indicated by a number of family and twin studies for systemic lupus erythematosus (SLE) and the demonstration of an increased frequency of HLA-DR2, HLA-DR3, and HLA-DR4 null alleles in patients with SLE.

Significant controversy still exists regarding the role of oral contraceptives in inducing SLE. Antinuclear antibodies (ANAs) associated with LP were reverted to negative when the drug was discontinued. Some patients using the intrauterine device complain of dysmenorrhea and recurrent infections, especially those taking prednisone and cytotoxic drugs. Although the incidence of SLE in families was initially believed to be no greater than in the general population, this is no longer thought to be true.

PL molecules are ubiquitous in nature and are present in the inner surface of the cell (ie, on the inner or outer surface of the cell membrane or intracellular organelles) and in microorganisms. Therefore, during infectious disease processes, including viral (eg, HIV, Epstein-Barr virus [EBV], cytomegalovirus [CMV], adenoviruses), bacterial (eg, bacterial endocarditis, tuberculosis, Mycoplasma pneumonia), spirochetal (eg, syphilis, leptospirosis, Lyme disease), and parasitic (eg, malaria infection), the disruption of cellular membranes may occur during cell damage. PLs release and stimulate aPL antibodies.

The SWISS PROT protein database revealed high homology between the hexapeptides that bind to ILA-1, ILA-3, and H-3 mAbs and the membrane particles of different bacteria and viruses. The sequence LKTPRV showed homology to 8 different bacteria (eg, Pseudomonas aeruginosa) and homologies to 5 types of viruses (ie, polyoma virus, human CMV, adenovirus). The sequence TL-RVYK shows homology to 8 different bacteria, including Haemophilus influenzae, Neisseria gonorrhoeae, and Shigella dysenteriae, and to viruses such as EBV and HIV. Therefore, data might support the theory predicting that epitope mimicry is involved in the propagation of the autoimmune status.

Autoantibodies include the following:

  • Antiphospholipid
  • Anticardiolipin
  • Antiphosphatidylinositol
  • Antiphosphatidylserine
  • Antiphosphatidylcholine
  • Anti–beta-2 glycoprotein I
  • Antinuclear antibody
  • Anti-DNA (double- or single-stranded)
  • Anti-Sjögren syndrome A antibody (Ro)
  • Anti-Sjögren syndrome B antibody (Ia)

Antibodies against microorganism(s) associated with infection or vaccination include the following:

  • Antibacterial PL
  • Antibacterial protein
  • Antiviral glycoprotein
  • Anti-Sjögren syndrome A antibody (Ro) and anti-Sjögren syndrome B antibody (Ia): These are associated with neonatal lupus erythematosus, including congenital complete heart block. These antibodies are usually present in patients with Sjögren syndrome.
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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.

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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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