Clopidogrel Desensitization: Case Report and Review of Published Protocols

Abstract

The antiplatelet drug clopidogrel is an oral thienopyridine derivative that has been extensively used for the treatment and secondary prevention of a variety of cardiovascular diseases. Although clopidogrel is well tolerated by most patients, rare but serious hypersensitivity reactions have been documented, including cutaneous reactions and angioedema. An alternative thienopyridine that may be substituted for clopidogrel is ticlopidine; however, deleterious side effects from ticlopidine may occur, including diarrhea, neutropenia, and thrombocytopenia purpura, and cross-reactivity has been documented between these two thienopyridines. In cases of bare-metal stent deployment, cilostazol may be a safe and effective alternative; however, limited therapeutic data are available. In such cases, providers may need to administer a clopidogrel desensitization protocol; three clopidogrel desensitization protocols have been published. We describe a 58-year-old man who developed a generalized diffuse rash along his abdomen within 2 weeks of exposure to clopidogrel after drug-eluting stent placement. Clopidogrel was discontinued, and ticlopidine was begun. The rash resolved within 3 days of clopidogrel discontinuation. Using the Naranjo adverse drug reaction probability scale, we determined that the probability of clopidogrel causing the rash was probable (score of 8). Ticlopidine was subsequently discontinued due to severe diarrhea. Because of the patient's implanted stent and high risk for possible thrombosis, an 8-hour clopidogrel desensitization protocol was devised and successfully used in this patient, who continued to receive clopidogrel over the next year without rash recurrence. Based on our experience and the literature reviewed, administration of a clopidogrel desensitization protocol in patients with a history of isolated cutaneous hypersensitivity reactions, including angioedema, to clopidogrel can be a safe therapeutic alternative to ticlopidine or cilostazol.