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) to be 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 require only treatment with heparin. Treatment is optional for patients with no history of pregnancy loss or thrombosis.

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.

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 does 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.

Heparin

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Heparin is indicated to decrease the risk of thrombosis and pregnancy loss in pregnant women with APS.

It augments the activity of antithrombin III and prevents the conversion of fibrinogen to fibrin. Heparin does not actively lyse but is able to inhibit further thrombogenesis. The drug prevents reaccumulation of clot after spontaneous fibrinolysis.

Enoxaparin (Lovenox)

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Enoxaparin, an LMWH, is indicated to decrease the risk of thrombosis and pregnancy loss in pregnant women with APS. It prevents deep venous thrombosis (DVT), which may lead to pulmonary embolism in patients undergoing surgery who are at risk for thromboembolic complications. Enoxaparin enhances the inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases the inhibition of factor Xa.

Dalteparin (Fragmin)

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Dalteparin is indicated for the prevention of DVT, which may lead to PE. It enhances the inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, dalteparin preferentially increases the inhibition of factor Xa. The average duration of treatment is 7-14 days.

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.

Aspirin (Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin, Ibu, Advil, Motrin)

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Aspirin's antiplatelet effect is indicated to decrease the risk of thrombosis and pregnancy loss in pregnant women with APS. It inhibits prostaglandin synthesis, preventing the formation of platelet-aggregating thromboxane A2. Aspirin is used in low dose to inhibit platelet aggregation and to improve complications of venous stasis and thrombosis.

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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. [QxMD MEDLINE Link].
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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. [QxMD MEDLINE Link].
Lefkou E, Mamopoulos A, Dagklis T, Vosnakis C, Rousso D, Girardi G. Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy. J Clin Invest. 2016 Aug 1. 126 (8):2933-40. [QxMD MEDLINE Link].
[Guideline] Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2020 Feb 23. 76 (1):9-16. [QxMD MEDLINE Link]. [Full Text].

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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

Ronald M Ramus, MD Professor of Obstetrics and Gynecology, Director, Division of Maternal-Fetal Medicine, Virginia Commonwealth University School of Medicine

Ronald M Ramus, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Medical Society of Virginia, 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

Sections Antiphospholipid Syndrome and Pregnancy
Overview
Presentation
DDx
Workup
Treatment
Guidelines
Medication
Tables
References

Feature	Management
Feature	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

Antiphospholipid Syndrome and Pregnancy Medication

Medication Summary

Anticoagulants, Hematologic