Abstract
Diffuse alveolar hemorrhage after percutaneous coronary intervention is a rare complication that has been mostly reported in association with glycoprotein IIb/IIIa inhibitors. We herein report a case of a 64-year-old male who developed a diffuse pulmonary hemorrhage after coronary stent implantation for ST-elevation myocardial infarction. Diagnostic bronchoscopy determined the hemorrhage to be a bland pulmonary hemorrhage, and this pattern suggested that combination therapy with aspirin and ticlopidine was therefore the most likely cause. The combination of aspirin and thienopyridine agents is a routine therapeutic protocol for patients after coronary stent implantation. Therefore, physicians should be aware that this dual antiplatelet therapy might sometimes induce fatal complications.
1
Introduction
Dual antiplatelet therapy with aspirin in combination with thienopyridine agents is in widespread use to improve the outcome of percutaneous coronary intervention. Bleeding complications caused by the dual antiplatelet therapy are common clinical problems, and the incidence of bleeding events has been reported to be up to 32.4%; however, most of them tend to be minor complications, including easy bruising, bleeding from small cuts, petechia and ecchymosis . Although the rate of major bleeding among patients with non-ST-elevation acute coronary syndrome varies widely in literature based on various factors, such as background of included patients, bleeding definitions, antithrombotic agents and so on, the incidences are between 0.9% and 5.7% . Recent retrospective registry data from 40 812 patients with acute myocardial infarction indicated that the incidence of nonfatal and fatal bleeding during a mean follow-up of 476.5 days was 4.5% and 0.3%, respectively . While gastrointestinal bleeding is a common nonfatal bleeding event , the incidence of fatal respiratory tract bleeding was 0.9%.
Diffuse alveolar hemorrhage is an uncommon, but acute and life-threatening event. A number of diseases can cause pulmonary bleeding, and pulmonary bleeding can accompany Wegener granulomatosis, microscopic polyangiitis, Goodpasture syndrome, connective tissue disorders, antiphospholipid antibody syndrome, infectious or toxic exposures and neoplastic conditions . In addition, the administration of antiplatelet medication can also cause such bleeding. Glycoprotein IIb/IIIa inhibitors, in combination with other antiplatelet drugs, have been the most commonly reported drugs associated with alveolar hemorrhage, and Kalra et al. reported that the incidence was 0.27%, while no cases developed among 5412 patients who underwent coronary procedures without abciximab . We herein report a case with a fatal bleeding complication of diffuse alveolar hemorrhage induced by dual antiplatelet therapy with aspirin and ticlopidine after coronary stent implantation for ST-elevated myocardial infarction.
2
Case reports
A 64-year-old male was transferred to our hospital because of sudden delirium. He had experienced vomiting and chest discomfort before suffering delirium. His past medical history lacked any details, but he had not visited a clinic regularly. On arrival, his femoral pulse was palpable, but his cuff blood pressure could not be measured. His electrocardiogram revealed ST elevations in the anterolateral leads and reciprocal ST depressions in the inferior leads ( Fig. 1 ). Transthoracic echocardiography demonstrated severe hypokinesis at the anteroseptal and lateral–posterior walls. He was diagnosed as having an ST-elevation myocardial infarction with shock and was treated with dopamine and oxygen. After the bolus administration of unfractionated heparin (10 000 units), intraaortic balloon pumping inserted via the right femoral artery was started, and coronary angiography showed 99% stenosis in the left main trunk with Thrombolysis in Myocardial Infarction 2 flow. A bare metal stent was deployed in the left main trunk lesion, and the slow flow was restored. However, since the patient had not yet recovered from the state of shock, percutaneous cardiopulmonary bypass was also started via the left femoral artery and vein with continuous infusion of unfractionated heparin, the dose of which was adjusted based on the values of the activated partial thromboplastin time or activated clotting time, both of which were monitored every 6 h. Nifekalant, a pure potassium channel antagonist, was administered intravenously because of an episode of ventricular fibrillation during coronary angiography. The patient also received omeprazole plus oral dual antiplatelet therapy with aspirin at 100 mg/day and ticlopidine at 200 mg/day without a loading dose because clopidogrel had not been approved in Japan at that time.
His hemodynamics were improving, and the percutaneous cardiopulmonary bypass was successfully withdrawn on the third day after admission ( Fig. 2 ). The arterial partial pressure oxygen/fraction of inspired oxygen ratio was 255 mmHg on the fourth day. The patient’s blood pressure with intraaortic balloon pumping was 110/75 mmHg, and the chest X-ray did not show definite infiltrates. Ampicillin/sulbactam was administrated empirically for a fever of unknown origin. Nevertheless , the patient suddenly fell into acute respiratory failure because of massive hemoptysis that resulted in an obstruction of an intubation tube with coagula on the fifth day. Exchanging the intubation tube led to the immediate recovery from his respiratory distress, while the chest X-ray revealed a new infiltrate in the right lung field. The dual antiplatelet therapy and the heparin infusion were suspected to be the cause of the bronchostaxis. His prothrombin time–international normalized ratio and activated partial thromboplastin time were 1.12 and 45.5 s, respectively, but his platelet count decreased to 69×10 9 from 210×10 9 /L. The hemoglobin level remained at 10.4 g/dl, and he did not receive a blood transfusion. The continuous infusion of unfractionated heparin and the intraaortic balloon pumping were withdrawn on the sixth day ( Fig. 2 ). The dual antiplatelet therapy was continued for fear of subacute stent thrombosis. Unfortunately, massive hemoptysis occurred again on the next day. His chest radiograph showed new bilateral infiltrates ( Fig. 3 ), and bronchoscopy revealed diffuse hemorrhage on the bronchial wall at the bilateral lung field without edema of the bronchial wall ( Fig. 4 ). The prothrombin time–international normalized ratio was 1.24, and the platelet count recovered to 147×10 9 /L. His blood pressure was 108/68 mmHg, and right heart catheterization revealed that the mean pulmonary artery wedge pressure and the cardiac index were 16 mmHg and 2.3 L/min/m 2 , respectively. Because of severe hypoxemia, extracorporeal membrane oxygenation was started, but the patient thereafter suddenly collapsed. Despite changing the extracorporeal membrane oxygenation to percutaneous cardiopulmonary bypass, the patient died the same day. An autopsy was not performed at the request of the family.
2
Case reports
A 64-year-old male was transferred to our hospital because of sudden delirium. He had experienced vomiting and chest discomfort before suffering delirium. His past medical history lacked any details, but he had not visited a clinic regularly. On arrival, his femoral pulse was palpable, but his cuff blood pressure could not be measured. His electrocardiogram revealed ST elevations in the anterolateral leads and reciprocal ST depressions in the inferior leads ( Fig. 1 ). Transthoracic echocardiography demonstrated severe hypokinesis at the anteroseptal and lateral–posterior walls. He was diagnosed as having an ST-elevation myocardial infarction with shock and was treated with dopamine and oxygen. After the bolus administration of unfractionated heparin (10 000 units), intraaortic balloon pumping inserted via the right femoral artery was started, and coronary angiography showed 99% stenosis in the left main trunk with Thrombolysis in Myocardial Infarction 2 flow. A bare metal stent was deployed in the left main trunk lesion, and the slow flow was restored. However, since the patient had not yet recovered from the state of shock, percutaneous cardiopulmonary bypass was also started via the left femoral artery and vein with continuous infusion of unfractionated heparin, the dose of which was adjusted based on the values of the activated partial thromboplastin time or activated clotting time, both of which were monitored every 6 h. Nifekalant, a pure potassium channel antagonist, was administered intravenously because of an episode of ventricular fibrillation during coronary angiography. The patient also received omeprazole plus oral dual antiplatelet therapy with aspirin at 100 mg/day and ticlopidine at 200 mg/day without a loading dose because clopidogrel had not been approved in Japan at that time.
