Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Antiphospholipid Syndrome and Pregnancy Workup

  • Author: Teresa G Berg, MD, FACOG; Chief Editor: Thomas Chih Cheng Peng, MD  more...
 
Updated: Apr 15, 2015
 

Approach Considerations

As previously mentioned, the 1999 “international consensus statement for the diagnosis of antiphospholipid syndrome” provided a set of criteria for the diagnosis of APS. These were updated in 2006 to reflect new insights into the disease.

The diagnosis of APS requires that the patient have at least 1 clinical criterion and 1 laboratory criterion. The criteria for laboratory testing, which are consistent with current clinical management guidelines from the American Congress of Obstetricians and Gynecologists (ACOG), include the following[7, 8, 9] :

  • Anticardiolipin antibodies - Anticardiolipin (aCL) IgG or IgM antibodies present at moderate or high levels (ie, >40 GPL or MPL or >99th percentile) in the blood on 2 or more occasions at least 12 weeks apart
  • Lupus anticoagulant - LAC 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
  • Anti-beta 2 -glycoprotein I antibodies IgG or IgM - In titer above the 99th percentile for normal as defined by the laboratory performing the test, on 2 or more occasions at least 12 weeks apart

In a 3-year retrospective analysis by the European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS), the investigators indicated that all relevant laboratory studies should be obtained to avoid false-negative diagnoses and that levels may act as serologic markers for some cases.[2]

Imaging studies

Appropriate neurologic or imaging studies should be performed based on clinical findings; ie, a computed tomography (CT) or magnetic resonance imaging (MRI) scan can be carried out in the presence of central nervous system (CNS) symptoms.

Next

Laboratory Studies

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.

Systemic lupus erythematosus (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, however, is associated with an increased serum complement level.

LAC, aCL, anti-b2GPI, and aPS/PT studies

LAC is detected by phospholipid (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-beta2 -glycoprotein I 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-beta2 -glycoprotein I IgG or IgM isotype in serum or plasma that is greater than the 99th percentile for a normal population as defined by the laboratory performing the test.

In a study of 230 patients with SLE, Sciascia et al determined that combining tests for LAC, anti-beta2 -glycoprotein I, and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies provided greater diagnostic accuracy for APS than did other combinations of laboratory tests. The investigators also found that patients in whom all 3 tests were positive were at greater risk for clinical events, such as thrombosis or pregnancy loss, than were patients in whom only 1 or 2 of the tests were positive.[10]

Hematologic and serologic characteristics of APS

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

Lupus anticoagulant

Prolonged clotting times occur 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.

VDRL test

False-positive results from the venereal disease research laboratory (VDRL) test may occur.

Previous
Next

Histologic Findings

As previously mentioned, clinical evidence of glomerulonephritis is found in more than 50% of cases of SLE. Histologically, the following 6 classes of lupus glomerulonephritis have been recognized by the World Health Organization (WHO):

  • 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
Previous
 
 
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, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Thomas Chih Cheng Peng, MD Professor (Collateral), Department Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine, VCU Health System

Thomas Chih Cheng Peng, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Gregory Locksmith, MD Associate Director, Division of Gynecology, Department of Medical Education, Orlando Regional Health System

Disclosure: Nothing to disclose.

Bruce A Meyer, MD, MBA Executive Vice President for Health System Affairs, Executive Director, Faculty Practice Plan, 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.

Bogdan Nowicki, MD, PhD Head of Infectious Disease Laboratory, Associate Professor, Departments of Microbiology and Immunology, Obstetrics and Gynecology, University of Texas Medical Branch at Galveston

Disclosure: Nothing to disclose.

Stella Nowicki, DDS Head of Infectious Diseases Laboratory, Associate Professor, Departments of Obstetrics and Gynecology, Microbiology and Immunology, University of Texas Medical Branch at Galveston

Disclosure: Nothing to disclose.

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

References
  1. Fischer-Betz R, Specker C, Brinks R, Schneider M. Pregnancy outcome in patients with antiphospholipid syndrome after cerebral ischaemic events: an observational study. Lupus. 2012 Oct. 21(11):1183-9. [Medline].

  2. Alijotas-Reig J, Ferrer-Oliveras R, Ruffatti A, et al. The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): A survey of 247 consecutive cases. Autoimmun Rev. 2015 May. 14(5):387-395. [Medline].

  3. Bouvier S, Cochery-Nouvellon E, Lavigne-Lissalde G, et al. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood. 2014 Jan 16. 123(3):404-13. [Medline].

  4. Asherson RA, Khamashta MA, Ordi-Ros J, et al. The "primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore). 1989 Nov. 68(6):366-74. [Medline].

  5. Kochenour NK, Branch DW, Rote NS, Scott JR. A new postpartum syndrome associated with antiphospholipid antibodies. Obstet Gynecol. 1987 Mar. 69(3 Pt 2):460-8. [Medline].

  6. Cowchock FS, Reece EA, Balaban D, Branch DW, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol. 1992 May. 166(5):1318-23. [Medline].

  7. Wilson WA, Gharavi AE, Koike T, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum. 1999 Jul. 42(7):1309-11. [Medline].

  8. [Guideline] Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb. 4(2):295-306. [Medline].

  9. [Guideline] The American College of Obstetricians and Gynecologists. Antiphospholipid Syndrome. ACOG Practice Bulletin. January/2011. 118:1-8. [Full Text].

  10. Sciascia S, Murru V, Sanna G, Roccatello D, Khamashta MA, Bertolaccini ML. Clinical accuracy for diagnosis of antiphospholipid syndrome in systemic lupus erythematosus: evaluation of 23 possible combinations of antiphospholipid antibody specificities. J Thromb Haemost. 2012 Dec. 10(12):2512-8. [Medline].

 
Previous
Next
 
Table. Proposed Management for Women With aPL Antibodies
Feature Management
Pregnant Nonpregnant
APS with prior fetal death or recurrent pregnancy loss Heparin in prophylactic doses (15,000-20,000 U of unfractionated heparin or equivalent per day) 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 stroke Heparin 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 thrombosis No 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
LGBSS High-dose IVIG at 400-1500 mg/kg/day for several days IVIG at 400-1500 mg/kg/d for several days
aPL Antibodies Without APS
LAC or medium to high level of aCL IgG No treatment No treatment
Low levels of aCL IgG, only aCL IgM, or only aCL IgA without LA, aPL, or aCL No treatment No treatment
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.