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Antiphospholipid Syndrome Medication

  • Author: Suneel Movva, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Jul 01, 2016
 

Medication Summary

Therapeutic agents are based on anticoagulant properties, and benefits are weighed carefully against their significant risks. Life-long treatment with warfarin (see Treatment) is standard for recurrent thrombotic events.

For obstetric patients with antiphospholipid syndrome (APS) (see Obstetric considerations), the standard therapy is subcutaneous LMWH and low-dose aspirin.

Heparin therapy may be administered in several regimens, as follows:

  • Thrombotic events are initially treated with intravenous infusion of unfractionated heparin or therapeutic doses of LMWH.
  • Subcutaneous LMWH (enoxaparin [Lovenox]) may also be used for obstetric or thrombosis prophylaxis. Lower doses (20-40 mg/d SC) are used to prevent fetal loss, while higher doses (1 mg/kg q12h or 1.5 mg/kg/d) are used for thrombosis prophylaxis in patients (pregnant or nonpregnant) who have had prior thrombotic events.

Patients who require heparin administration throughout pregnancy should receive calcium and vitamin D supplementation to help avoid heparin-induced osteoporosis. When monitoring heparin therapy, note that the aPTT may be unreliable in the presence of circulating LA with a baseline elevated aPTT. In this case, factor Xa may be helpful.

Recent studies have begun to cast doubt on the value of heparin therapy in pregnancy, however. Canadian investigators conducted a randomized, controlled trial comparing LMWH plus aspirin with aspirin alone in women with recurrent pregnancy loss, almost half of whom had antiphospholipid (aPL) antibodies; the trial was halted when interim analysis showed that women receiving aspirin alone had the same rate of live births and a lower rate of pregnancy loss compared with those who also received LMWH.[20]

The antithrombotic properties of hydroxychloroquine have long been recognized and may be considered in the prophylactic treatment of a patient with SLE and a positive aPL antibody test result[16] . Case reports suggest that clopidogrel may be effective because of its antiplatelet effect. Recently, statins have been suggested to have potential antithrombotic effects. Statins are recommended for APS patients with hyperlipidemia and, possibly, in aPL patients with recurrent thromboses despite adequate anticoagulation.[16]

In addition to full anticoagulation, plasma exchange and corticosteroids are generally used in the treatment of CAPS. Intravenous immunoglobulin or cyclophosphamide may also be considered in selected patients with CAPS. For example, a recent retrospective study reported a decrease in late pregnancy complications in women with APS who received 0.2 g/kg of intravenous immunoglobulin.[21]

Rituximab has shown benefit in controlling severe thrombocytopenia, skin ulcers, and cognitive dysfunction that can be associated with APS.[16]

Case reports have described the use of eculizumab, a humanized monoclonal antibody against C5 complement protein, in CAPS, and in aPL-positive patients undergoing renal transplantation.[22]

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Anticoagulants

Class Summary

Standard therapy for thrombosis commonly consists of intravenous heparin followed by warfarin. Treatment of a pregnant patient with a history of recurrent fetal loss is controversial but generally includes subcutaneous heparin and aspirin.

Warfarin (Coumadin)

 

Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Long-term warfarin is DOC for APS in patients with recurrent thrombotic events. Titrated dose suggested to maintain INR in therapeutic range (see above).

Enoxaparin (Lovenox)

 

LMWH. Most experience; other LMWH preparations available.

Heparin

 

Used in inpatient settings as continuous infusion during conversion to warfarin therapy until a therapeutic INR is achieved. May be administered SC as substitute for warfarin during attempted pregnancy or for temporary anticoagulation during warfarin loading in outpatient setting.

Aspirin (Anacin 81, Ascriptin, Bayer Aspirin)

 

Although not proven effective when used alone, most clinicians use aspirin with SC heparin in pregnant patients with APS. Begin aspirin as soon as conception is attempted.

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Antimalarials

Class Summary

As prophylactic therapy, these agents may have an additional anticoagulant effect in patients with SLE.

Hydroxychloroquine (Plaquenil)

 

Most common antimalarial used in APS, mostly because of excellent safety profile.

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Immunosuppressive agents

Class Summary

Consider immunosuppressive agents in select cases (eg, refractory APS, CAPS).

Cyclophosphamide (Cytoxan, Neosar)

 

Chemically related to nitrogen mustards. As an alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. Has not been shown to be effective in APS.

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Corticosteroids

Class Summary

In selected cases with specific nonthrombotic autoimmune manifestations (eg, clinically significant thrombocytopenia), corticosteroids may be considered.

Prednisone (Deltasone, Orasone, Sterapred)

 

Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Useful in treating cytopenias.

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Immunomodulatory therapy agents

Class Summary

These agents interfere with processes that promote immune reactions resulting from diverse stimuli.

Intravenous immune globulins, 5% (Gammagard, Gamimune)

 

Following features may be relevant to efficacy: neutralization of circulating myelin antibodies through antiidiotypic antibodies, down-regulation of proinflammatory cytokines (including IFN-gamma), blockade of Fc receptors on macrophages, suppression of helper/inducer T and B cells and augmentation of suppressor T cells, blockade of the complement cascade, promotion of remyelination, and 10% increase in CSF IgG. May be effective in APS.

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Contributor Information and Disclosures
Author

Suneel Movva, MD Fellow in Rheumatology, Division of Rheumatology, Allergy and Immunology, Winthrop University Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Steven Carsons, MD Chief, Division of Rheumatology, Allergy and Immunology, Winthrop University Hospital; Professor of Medicine, Stony Brook University School of Medicine

Steven Carsons, MD is a member of the following medical societies: American College of Rheumatology, New York Academy of Sciences, Society for Experimental Biology and Medicine

Disclosure: Nothing to disclose.

Elise Belilos, MD Section Head of Rheumatology, Division of Rheumatology, Allergy and Immunology, Winthrop University Hospital; Assistant Professor of Clinical Medicine, Department of Internal Medicine, Stony Brook University School of Medicine

Elise Belilos, MD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Janssen<br/>Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Genentech; Pfizer; Questcor.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Carlos J Lozada, MD Director of Rheumatology Fellowship Training Program, Professor of Clinical Medicine, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine

Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Received honoraria from Pfizer for consulting; Received grant/research funds from AbbVie for other; Received honoraria from Heel for consulting.

Acknowledgements

The authors gratefully acknowledge the contributions of Amiel Tokayer, MD.

References
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