Antiphospholipid Antibody Syndrome and Pregnancy Medication

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

Medication Summary

In women with well-recognized obstetric APS, anticoagulant prophylaxis is recommended during pregnancy and the postpartum period. Pregnant women with APS are considered at risk for thrombosis and pregnancy loss. Data suggest low-dose aspirin and heparin (either unfractionated heparin or LMWH) are the treatments of choice for prevention of pregnancy loss in pregnant women with APS and previous pregnancy losses. Pregnant women with APS and a history of thrombosis but no pregnancy loss only require treatment with heparin. Treatment is optional for patients with no history of pregnancy loss or thrombosis.

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Heparin compounds

Class Summary

Unfractionated intravenous (IV) heparin and fractionated subcutaneous (SC) LMWH are the 2 choices for initial anticoagulation therapy. Warfarin therapy may be initiated in the postpartum stage.

These are used in the treatment or prophylaxis of clinically evident intravascular thrombosis. Special precaution should be exercised in obstetrical emergencies or massive liver failure.

LMWHs may also be used. Similar to unfractionated heparin, LMWHs are a class of anticoagulants termed glycosaminoglycans. LMWHs are derived from unfractionated heparin but have smaller, more standard average masses than heterogeneous unfractionated heparin.

Unlike standard heparin, LMWHs have higher specificity for factor Xa and have fewer effects on platelet activity. As a result, LMWH may cause bleeding less often, while still retaining anticoagulant effects. LMWHs may be associated with less risk of heparin-induced osteoporosis.

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Heparin

 

Indicated to decrease risk of thrombosis and pregnancy loss in pregnant women with APS.

Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

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Enoxaparin (Lovenox)

 

Indicated to decrease risk of thrombosis and pregnancy loss in pregnant women with APS.

Prevents DVT, which may lead to pulmonary embolism in patients undergoing surgery who are at risk for thromboembolic complications. Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases inhibition of factor Xa.

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Antiplatelet agents

Class Summary

Randomized controlled trials demonstrate improved fetal survival when pregnant women with APS and prior pregnancy losses are treated with low-dose aspirin plus heparin compared with low-dose aspirin alone.

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Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)

 

Antiplatelet effect indicated to decrease risk of thrombosis and pregnancy loss in pregnant women with APS. Inhibits prostaglandin synthesis, preventing formation of platelet-aggregating thromboxane A2. Used in low dose to inhibit platelet aggregation and improve complications of venous stasis and thrombosis.

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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

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

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

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

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

  5. Asherson RA, Cervera R, Piette J-C et al. Catastrophic antiphospholipid syndrome: Clinical and laboratory features of 50 patients. Medicine. 1918;77:195.

  6. Berman J, Girardi G, Salmon JE. TNF-alpha is a critical effector and a target for therapy in antiphospholipid antibody-induced pregnancy loss. J Immunol. Jan 1 2005;174(1):485-90. [Medline].

  7. Blank M, Cohen J, Toder V, Shoenfeld Y. Induction of anti-phospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies. Proc Natl Acad Sci U S A. Apr 15 1991;88(8):3069-73. [Medline].

  8. Blank M, Shoenfeld Y, Cabilly S, et al. Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides. Proc Natl Acad Sci U S A. Apr 27 1999;96(9):5164-8. [Medline].

  9. Bocciolone L, Meroni P, Parazzini F, et al. Antiphospholipid antibodies and risk of intrauterine late fetal death. Acta Obstet Gynecol Scand. May 1994;73(5):389-92. [Medline].

  10. Branch DW, Hatasaka HH. Antiphospholipid antibodies and infertility: fact or fallacy. Lupus. 1998;7 Suppl 2:S90-4. [Medline].

  11. Branch DW, Scott JR, Kochenour NK, Hershgold E. Obstetric complications associated with the lupus anticoagulant. N Engl J Med. Nov 21 1985;313(21):1322-6. [Medline].

  12. Branch DW, Silver R, Pierangeli S, et al. Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome. Obstet Gynecol. Apr 1997;89(4):549-55. [Medline].

  13. Caligaris-Cappio F, Bertero MT, Converso M, et al. Circulating levels of soluble CD30, a marker of cells producing Th2- type cytokines, are increased in patients with systemic lupus erythematosus and correlate with disease activity. Clin Exp Rheumatol. May-Jun 1995;13(3):339-43. [Medline].

  14. Casali P, Schettino EW. Structure and function of natural antibodies. Curr Top Microbiol Immunol. 1996;210:167-79. [Medline].

  15. Christiansen OB, Ulcova-Gallova Z, Mohapeloa H, Krauz V. Studies on associations between human leukocyte antigen (HLA) class II alleles and antiphospholipid antibodies in Danish and Czech women with recurrent miscarriages. Hum Reprod. Dec 1998;13(12):3326-31. [Medline].

  16. de Groot PG, Horbach DA, Derksen RH. Protein C and other cofactors involved in the binding of antiphospholipid antibodies: relation to the pathogenesis of thrombosis. Lupus. Oct 1996;5(5):488-93. [Medline].

  17. Derksen RH, Khamashta MA, Branch DW. Management of the obstetric antiphospholipid syndrome. Arthritis Rheum. Apr 2004;50(4):1028-39. [Medline].

  18. Gharavi EE, Chaimovich H, Cucurull E, et al. Induction of antiphospholipid antibodies by immunization with synthetic viral and bacterial peptides. Lupus. 1999;8(6):449-55. [Medline].

  19. Hagiwara E, Gourley MF, Lee S, Klinman DK. Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin-10:interferon-gamma- secreting cells in the peripheral blood. Arthritis Rheum. Mar 1996;39(3):379-85. [Medline].

  20. Harris EN, Pierangeli SS, Gharavi AE. Diagnosis of the antiphospholipid syndrome: a proposal for use of laboratory tests. Lupus. 1998;7 Suppl 2:S144-8. [Medline].

  21. Hayem G, Kassis N, Nicaise P, et al. Systemic lupus erythematosus-associated catastrophic antiphospholipid syndrome occurring after typhoid fever: a possible role of Salmonella lipopolysaccharide in the occurrence of diffuse vasculopathy- coagulopathy. Arthritis Rheum. May 1999;42(5):1056-61. [Medline].

  22. Ikematsu W, Luan FL, La Rosa L, et al. Human anticardiolipin monoclonal autoantibodies cause placental necrosis and fetal loss in BALB/c mice. Arthritis Rheum. Jun 1998;41(6):1026-39. [Medline].

  23. Jablonowska B, Selbing A, Palfi M, et al. Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study. Hum Reprod. Mar 1999;14(3):838-41. [Medline].

  24. Khamashta MA, Cuadrado MJ, Mujic F, et al. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. Apr 13 1995;332(15):993-7. [Medline].

  25. Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GR. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. Apr 13 1995;332(15):993-7. [Medline].

  26. Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol. May 1996;174(5):1584-9. [Medline].

  27. Lockshin MD, Druzin ML, Goei S, et al. Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus. N Engl J Med. Jul 18 1985;313(3):152-6. [Medline].

  28. Machin SJ. Platelets and antiphospholipid antibodies. Lupus. Oct 1996;5(5):386-7. [Medline].

  29. Matsuura E, Igarashi Y, Fujimoto M, et al. Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. J Immunol. Jun 15 1992;148(12):3885-91. [Medline].

  30. McFarland HF. Complexities in the treatment of autoimmune disease. Science. Dec 20 1996;274(5295):2037-8. [Medline].

  31. Oshiro BT, Silver RM, Scott JR, et al. Antiphospholipid antibodies and fetal death. Obstet Gynecol. Apr 1996;87(4):489-93. [Medline].

  32. Pal D, Dalal BS, Haldar KK, et al. The prevalence of hepatitis D in hepatitis B patients--a hospital based study. Indian J Public Health. Jan-Mar 1996;40(1):22-3. [Medline].

  33. Pierro E, Cirino G, Bucci MR, et al. Antiphospholipid antibodies inhibit prostaglandin release by decidual cells of early pregnancy: possible involvement of extracellular secretory phospholipase A2. Fertil Steril. Feb 1999;71(2):342-6. [Medline].

  34. Piona A, La Rosa L, Tincani A, et al. Placental thrombosis and fetal loss after passive transfer of mouse lupus monoclonal or human polyclonal anti-cardiolipin antibodies in pregnant naive BALB/c mice. Scand J Immunol. May 1995;41(5):427-32. [Medline].

  35. Puri V, Bookman A, Yeo E, et al. Antiphospholipid antibody syndrome associated with hepatitis C infection. J Rheumatol. Feb 1999;26(2):509-10. [Medline].

  36. Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ. Jan 25 1997;314(7076):253-7. [Medline].

  37. Richaud-Patin Y, Alcocer-Varela J, Llorente L. High levels of TH2 cytokine gene expression in systemic lupus erythematosus. Rev Invest Clin. Jul-Aug 1995;47(4):267-72. [Medline].

  38. Roubey RA, Eisenberg RA, Harper MF, Winfield JB. "Anticardiolipin" autoantibodies recognize beta 2-glycoprotein I in the absence of phospholipid. Importance of Ag density and bivalent binding. J Immunol. Jan 15 1995;154(2):954-60. [Medline].

  39. Segal R, Bermas BL, Dayan M, et al. Kinetics of cytokine production in experimental systemic lupus erythematosus: involvement of T helper cell 1/T helper cell 2-type cytokines in disease. J Immunol. Mar 15 1997;158(6):3009-16. [Medline].

  40. Silver RM, Porter TF, van Leeuween I, et al. Anticardiolipin antibodies: clinical consequences of "low titers". Obstet Gynecol. Apr 1996;87(4):494-500. [Medline].

  41. Sletnes KE, Wisloff F, Moe N, Dale PO. Antiphospholipid antibodies in pre-eclamptic women: relation to growth retardation and neonatal outcome. Acta Obstet Gynecol Scand. Feb 1992;71(2):112-7. [Medline].

  42. Spinnato JA, Clark AL, Pierangeli SS, Harris EN. Intravenous immunoglobulin therapy for the antiphospholipid syndrome in pregnancy. Am J Obstet Gynecol. Feb 1995;172(2 Pt 1):690-4. [Medline].

  43. Tincani A, Spatola L, Prati E, et al. The anti-beta2-glycoprotein I activity in human anti-phospholipid syndrome sera is due to monoreactive low-affinity autoantibodies directed to epitopes located on native beta2-glycoprotein I and preserved during species' evolution. J Immunol. Dec 15 1996;157(12):5732-8. [Medline].

  44. Van Es JH, Aanstoot H, Gmelig-Meyling FH, et al. A human systemic lupus erythematosus-related anti-cardiolipin/single- stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene. J Immunol. Sep 15 1992;149(6):2234-40. [Medline].

  45. Vogt E, Ng AK, Rote NS. A model for the antiphospholipid antibody syndrome: monoclonal antiphosphatidylserine antibody induces intrauterine growth restriction in mice. Am J Obstet Gynecol. Feb 1996;174(2):700-7. [Medline].

  46. Yetman DL, Kutteh WH. Antiphospholipid antibody panels and recurrent pregnancy loss: prevalence of anticardiolipin antibodies compared with other antiphospholipid antibodies. Fertil Steril. Oct 1996;66(4):540-6. [Medline].

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

  48. [Guideline] Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295-306.

 
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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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