A 68-year-old male developed pruritic and exanthematous eruptions over a 24-hour period. He had a history of angina for the past 6 months, and he underwent elective percutaneous coronary intervention in the left anterior descending artery and left circumflex artery on June 24, 2015. Three drug-eluting stents were inserted (2 paclitaxel eluting stents, YINYI Biomedical Materials R&D Center Co., Ltd., Liaoning, China; and 1 sirolimus eluting stent, Lepu Medical Technology Co., Ltd., Beijing, China). All 3 stents were made of 316L stainless steel. Moreover, he also had a previous history of hypertension and hypercholesterolaemia. He had no history of prior drug allergy.\nDrugs included aspirin, ticagrelor, bisoprolol, and rosuvastatin. He has taken aspirin, bisoprolol, and rosuvastatin for the last 5 months, showing a good tolerance. After taking ticagrelor for 2 days, he developed pruritic and maculopapular rash on his bilateral costal margin, which was then generalized to the trunk (predominantly affected the chest and abdomen). His extremities were not affected, with no angioedema, no fever, and no arthralgia.\nThe laboratory test result showed an elevation in the leukocyte count (11.4 ×109/L) and in the neutrophil count (8.21 ×109/L). The lymphocyte count was 1.72 ×109/L and the eosinophil count was 0.58 ×109/L. The liver function test results were as follows: alanine aminotransferase, 14 U/L; aspartate aminotransferase, 27 U/L; total protein, 61.9 g/L; albumin, 40.2 g/L; total bilirubin, 36.8 µmol/L; direct bilirubin, 5.59 µmol/L; γ-glutamyltranspetidase, 61 U/L; total bile acid, 0.9 µmol/L; and lactate dehydrogenase, 380 U/L.\nHe showed to have a hypersensitive reaction to ticagrelor, and he was treated with antihistamines. Ticagrelor was switched to clopidogrel. Soon thereafter, his rash was gradually improved.\nHowever, 10 days later, he developed severe chest pain and received emergency coronary angiogram. Subacute definite stent thrombosis was confirmed, and thrombectomy was performed. After the procedure, a platelet function test was conducted, revealing a low response to clopidogrel.\nTo achieve therapeutic platelet aggregation inhibition, ticagrelor was reused under close supervision. Within approximately 2 hours, he developed generalized maculopapular rash in the whole trunk, which was resolved with intravenous corticosteroids. Ticagrelor was discontinued to avoid further hypersensitive reaction. Our patient showed delayed-type hypersensitivity reaction from the use of ticagrelor, represented in the form of generalized maculopapular rashes. Ticagrelor desensitization might not be appropriate for this patient.\nSwitching to other kinds of P2Y12 receptor antagonist antiplatelet drug was considered. Drugs that are structurally different from ticagrelor may be a good substitute for those with ticagrelor hypersensitivity. The chemical class of ticagrelor is cyclopentyl-triazolo-pyrimidine, and the other chemical class consists of thienopyridines (clopidogrel, prasugrel, ticlopidine) []. This patient presented a low response to clopidogrel and had suffered subacute in-stent thrombosis. Currently, prasugrel has not been approved for use in China. Ticlopidine has been associated with toxic side effects, such as rash, severe neutropenia, diarrhea, and thrombocytopenic purpura. Therefore, antithrombotic therapy was significantly difficult in this patient.\nThe patient ultimately received aspirin and warfarin as an antithrombotic treatment. He was given subcutaneous injection of low molecular weight heparin for 7 days. The regulated dose of warfarin was maintained in between 2 and 3 of the international normalized ratio (INR). During the follow-up period, our patient did not report any discomfort.
A 57-year-old man with significant history of ischaemic heart disease underwent elective percutaneous coronary intervention to the proximal left anterior descending artery with insertion of two drug-eluting stents in February 2014. He was commenced on dual antiplatelet therapy with the addition of clopidogrel to his regular aspirin. His other past medical history included hypertension and hypercholesterolaemia. He had no previous history of drug allergy or atopy.\nEleven days after commencement of clopidogrel he developed a generalised urticarial rash including his scalp and palms, with associated peripheral paraesthesia. He was treated with antihistamines and his clopidogrel was changed to ticagrelor.\nThirty-six hours after the introduction of ticagrelor, he represented with facial angioedema associated with left sided chest pain and dysphagia without respiratory compromise. Following the cessation of ticagrelor, the symptoms resolved with intramuscular adrenaline and intravenous corticosteroids and he was discharged home after a period of observation.\nFurther cardiology consultation recommended the trial of prasugrel under close supervision. Within two hours, he developed an urticarial reaction involving the hands, feet and groin, which initially resolved with antihistamine. After the third dose of prasugrel, he experienced chest, left arm and abdominal discomfort, with periorbital and lip angioedema. Although haemodynamically stable, he was diaphoretic and required oxygen therapy. Again, he improved with intramuscular adrenaline, intravenous f luid and oral and intravenous antihistamines. All investigations were unremarkable including the tryptase level which was only collected 36 hours post symptom onset.\nThe idea of trialling a fourth antiplatelet agent, ticlopidine, was briefly considered. Given his reaction to three antiplatelet agents, and after reviewing the molecular structure of all four drugs (), as well as available literature on clopidogrel sensitisation and its cross-reactivity towards ticlopidine and prasugrel, there was significant concern about the risk of similar but more severe and rapid onset hypersensitivity reaction. The patient ultimately underwent clopidogrel desensitisation with prednisolone cover. He successfully completed the programme without complication and was maintained on strict daily dose afterwards. He continues to take clopidogrel without adverse effects four months post desensitisation.