Bilateral upper extremity severe ecchymosis in a patient on alirocumab, rivaroxaban, and clopidogrel therapy

The PCSK9 inhibitors, alirocumab and evolocumab, are a new class of powerful LDL cholesterol lowering agents which allow previously unattainable lowering of LDL cholesterol (LDLC). Once past the necessarily restrictive confines of placebo-controlled clinical trials, in current medical practice, some patients with concomitant thromboembolism and arterial disease may also be taking potent anticoagulants and/or anti-platelet agents in addition to PCSK9 inhibitors. There are currently no reports on drug interactions and no warnings when alirocumab or evolocumab are used in conjunction with anticoagulants and/or anti-platelet therapy. Here, we present a case of patient with exceptional LDLC lowering (LDLC < 4 mg/dl) on alirocumab 150 mg/ml every 2 weeks and concomitant anti-platelet (clopidogrel 75 mg/day) and anti-coagulation therapy (rivaroxaban 10 mg/day) because of recurrent non-cardiogenic amaurosis fugax, and transient ischemic attacks, and ischemic stroke associated with heterozygosity for the G20210A prothrombin gene mutation. On this regimen, the patient developed gradually spreading intensive skin ecchymosis and bleeding on both arms. This resolved after stopping alirocumab, clopidogrel, and rivaroxaban, and did not reappear when clopidogrel and rivaroxaban were restarted without alirocumab.