Approach for the treatment of APS patients who have a recurrent clot while receiving anticoagulation
If an APS patient has a clot while on anticoagulation, it is imperative to establish that the patient was adequately anticoagulated at the time of the recurrent thrombosis. The APS patient on warfarin should have an INR of 2 to 3 and a confirmed chromogenic factor X level of ≤20%. If the patient is adequately anticoagulated and had a venous clot, then anticoagulation should be increased to an INR of 3 to 4 or the patient switched to LMWH if the INR is difficult to maintain in a therapeutic range consistently. If the patient has an arterial clot, then the INR can be increased to 3 to 4 and/or low-dose ASA or clopidogrel can be added.
If the APS patient clots while receiving LMWH, an antifactor Xa level should be checked to ensure it is in the therapeutic range. If the patient is therapeutic but has a venous clot and is on once-a-day enoxaparin, then using twice-a-day dosing may be helpful. If the patient has an arterial clot, then low-dose ASA can be added. If the patient is already on ASA, they can be switched to clopidogrel or use it in combination with ASA.
HCQ and statins are potential add-on treatments for patients who have recurrent thrombosis in spite of therapeutic doses of anticoagulant therapy with or without antiplatelet agents. HCQ has an antithrombotic effect based on platelet inhibition and protecting the annexin V anticoagulant shield from disruption by preventing anti-aPL-β2GPI complexes from binding to phospholipid membranes. Statins have immunomodulatory and antiinflammatory properties which suppress anti-β2GPI-mediated endothelial activation. Both of these may be beneficial in an APS patient refractory to treatment.
Use of heparin pumps, IVIG, plasma exchange, rituximab, corticosteroids, and/or immunosuppressive medications for patients who have recurrent thrombosis while on therapeutic anticoagulation is based on anecdotal reports. Recently, bortezomib (Velcade) has been successfully used in a few patients to deplete plasma cells and lower aPL ab levels and clot risk.
