A 69-year-old African gentleman with a medical history of coronary artery disease after percutaneous coronary intervention to his right coronary artery in 2014 for a non-ST-segment elevation myocardial infarction and prior contrast-media allergy presented to the emergency department with atypical angina.\nShortly after his arrival, he was seen by the emergency medicine physician who initiated an acute coronary syndrome antiplatelet regimen comprising both oral aspirin 325 mg and ticagrelor 180 mg. Vital signs revealed mild hypertension with a blood pressure of 147/94 mmHg, normal pulse rate of 74 beats per minute, and an oxygen saturation of 99% on pulse oximetry on room air. His physical examination was significant for left-sided chest wall tenderness only. A 12-lead electrocardiogram (EKG) revealed sinus rhythm with a 1st degree atrioventricular block and a left anterior fascicular block with prior inferior myocardial infarction. There were no acute ischemic changes. His cardiac biomarkers were normal (peak serum levels of creatine phosphokinase-MB fraction (CK-MB) and troponin T were 1.5 ng mL−1 (normal range, 1–5 ng mL−1) and 0.034 ng mL−1 (normal range, 0-0.1 ng mL−1), respectively) and did not reflect a myocardial infarction.\nApproximately 1 hour after ticagrelor administration, the patient reported a constellation of symptoms which included worsening chest pain, sudden-onset respiratory distress, and generalized urticaria. His repeat physical examination revealed new-onset periorbital edema and angioedema (). He was immediately administered 200 mg intravenous hydrocortisone, 100 mg intravenous ranitidine, and 10 mg intravenous chlorphenamine with nebulized albuterol and ipratropium, and his symptoms resolved shortly thereafter (within an hour).\nBased on the clinical scenario, the patient's tentative diagnosis was ticagrelor-induced hypersensitivity reaction with angioedema as this was the only new medication he was given (he was on daily maintenance aspirin for his CAD and previously tolerated a 1-year course of clopidogrel after drug-eluting stent implantation). It was also noted that he was not on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. He was subsequently transferred to cardiac care unit for further observation and supportive care. The following day, a 2D transthoracic echocardiogram revealed a preserved left ventricular ejection fraction of 60% without regional wall motion abnormalities. He reported that his symptoms were much improved and was hemodynamically stable. His clinical angioedema completely resolved. The patient's atypical angina completely abated, and subsequent cardiac biomarkers and electrocardiograms were unremarkable. As a result, inpatient coronary angiography was not pursued as his TIMI risk stratification was considered low to moderate risk, and outpatient exercise stress echocardiography was the preferred management strategy to assess for ischemia. He was safely discharged on guideline-recommended, optimal medical therapy comprising aspirin, clopidogrel (which he previously tolerated as DAPT for his prior stent implantation without any adverse effects), beta-blocker, mineralocorticoid receptor antagonist with high-intensity statin, and a tapered course of oral steroid therapy.
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.