Antiphospholipid Syndrome Medication
- Author: Suneel Movva, MD; Chief Editor: Herbert S Diamond, MD more...
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.
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 . 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.
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.
Rituximab has shown benefit in controlling severe thrombocytopenia, skin ulcers, and cognitive dysfunction that can be associated with APS.
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.
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.
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).
LMWH. Most experience; other LMWH preparations available.
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.
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.
As prophylactic therapy, these agents may have an additional anticoagulant effect in patients with SLE.
Most common antimalarial used in APS, mostly because of excellent safety profile.
Consider immunosuppressive agents in select cases (eg, refractory APS, CAPS).
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.
In selected cases with specific nonthrombotic autoimmune manifestations (eg, clinically significant thrombocytopenia), corticosteroids may be considered.
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
These agents interfere with processes that promote immune reactions resulting from diverse stimuli.
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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