Medication Summary
In deciding whether to initiate anticoagulant prophylaxis for patients with antiphospholipid syndrome (APS), the benefits of these agents must be weighed carefully against their significant risks. Life-long treatment with warfarin (see Treatment) is standard for patients who experience recurrent thrombotic events.
Heparin therapy may be administered in several regimens, as follows:
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Thrombotic events are initially treated with intravenous infusion of unfractionated heparin or therapeutic doses of subcutaneous low molecular weight heparin (LMWH) and low-dose aspirin.
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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 activated partial thromboplastin time (aPTT) may be unreliable in the presence of circulating antiphospholipid (aPL) antibodies with a baseline elevated aPTT. In this case, factor Xa may be helpful.
Hydroxychloroquine has antithrombotic properties and may be considered in the prophylactic treatment of a patient with SLE and a positive aPL antibody test result. [28] The use of hydroxychloroquine and intravenous immunoglobulin (IVIG) has been associated with good outcomes in pregnant women with APS who develop recurrent episodes of thrombosis or catastrophic APS (CAPS) despite receiving adequate antithrombotic treatment. [39]
In addition to full anticoagulation, plasma exchange and corticosteroids are generally used in the treatment of CAPS. IVIG or cyclophosphamide may be considered in selected patients with CAPS. However, cyclophosphamide increases the risk of first-trimester fetal loss, so its use in pregnant women should be reserved for severe, life-threatening or refractory manifestations during the second or third trimester. [34]
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. [28]
Rituximab has shown benefit in controlling severe thrombocytopenia, skin ulcers, and cognitive dysfunction that can be associated with APS. [28]
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. [40]
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.
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.
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.
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.
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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Antiphospholipid syndrome. Livedo reticularis.
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Antiphospholipid syndrome. Arterial thrombosis resulting in ischemia and necrosis of the foot.
