J Thromb Thrombolysis DOI 10.1007/s11239-013-1018-5
ST-segment elevation myocardial infarction treated with thrombolytic therapy in a patient with thrombotic thrombocytopenic purpura Jacob A. Doll • Jacob P. Kelly
Ó Springer Science+Business Media New York 2013
Abstract Acute myocardial infarction is a common complication of thrombotic thrombocytopenic purpura (TTP), but rarely the presenting manifestation. Antithrombotic therapy for myocardial infarction is rarely utilized in the setting of TTP because of elevated bleeding risk. We report a case of TTP presenting with ST-segment elevation myocardial infarction and treated with thrombolytic therapy. The resultant cardiac and neurological complications highlight the challenges of using evidence-based therapy for myocardial infarction in the setting of TTP. Keywords Myocardial infarction Thrombotic thrombocytopenic purpura Thrombolytic therapy
Introduction Cardiovascular complications of thrombotic thrombocytopenic purpura (TTP) are common and likely under-recognized [1]. Several case reports and small case series have documented myocardial infarction in the setting of TTP, but there is scant data on the course of disease in these patients [2–5]. Rarely, acute myocardial infarction (AMI) may be the presenting manifestation. Treatment of these patients is complicated by conflicting strategies for management of TTP and AMI. We report a case of TTP presenting with ST-segment elevation myocardial infarction (STEMI) and treated with thrombolytic therapy, with subsequent cardiac and neurological complications.
J. A. Doll (&) J. P. Kelly Duke University Medical Center, 2301 Erwin Road, DUMC 3845, Durham, NC 27710, USA e-mail: [email protected]
Case report A 56-year-old Caucasian man presented to a community hospital with complaint of 30 min of severe, sub-sternal chest pain radiating to his left shoulder. Prior to this episode, the patient was in his usual state of excellent health without known medical problems or risk factors for coronary artery disease. An ECG obtained at presentation demonstrated STsegment elevations in leads I and aVL with reciprocal STsegment depressions in leads II, III, and aVF. The acute myocardial infarction protocol was activated. The patient received 325 mg of aspirin, 600 mg of clopidogrel, a weight-based loading dose of heparin, morphine, and sublingual nitroglycerine without resolution of symptoms. Due to lack of cardiac catheterization facilities at the hospital, the patient then received 50 mg of intravenous tenecteplase and was transferred immediately to our hospital for further management and consideration of rescue percutaneous coronary intervention. On arrival to our hospital the patient was free of chest pain, and repeat ECG showed partial ([50 %) resolution of ST-segment elevations. He therefore met criteria for successful thrombolysis and immediate rescue cardiac catheterization was not performed. A complete blood count drawn on arrival was notable for a platelet count of 38,000. A platelet count from the referring hospital, drawn but not resulted prior to the administration of tenecteplase, clopidogrel, and aspirin, was 40,000. This thrombocytopenia prompted a concern for TTP. A blood smear was prepared which showed 3–5 schistocytes per high power field. Other classic signs of TTP, including altered mental status, fever, and renal dysfunction, were absent. However, no other etiology of micro-angiopathic hemolytic anemia was identified, and a diagnosis of TTP was made. Therapy with
123
J. A. Doll, J. P. Kelly
Fig. 1 12-lead electrocardiogram performed after resuscitation from cardiac arrest
corticosteroids and plasma exchange was initiated. All anticoagulant and anti-platelet medications were discontinued and cardiac catheterization was deferred. Echocardiography performed the morning of admission demonstrated an ejection fraction of 40 % with apical and antero-lateral hypokinesis. During the second round of plasma exchange, performed 1 day after admission, the patient had an abrupt worsening of mental status and suffered a cardiac arrest with pulseless electrical activity. With cardiopulmonary resuscitation he developed ventricular fibrillation, which was successfully defibrillated. The patient was intubated in the course of the resuscitation. A post-resuscitation ECG was notable for anterior and lateral ST-segment elevations (Fig. 1). A noncontrast CT scan of the head demonstrated a small subarachnoid hemorrhage in the right frontal lobe. Coronary angiography was deferred, due to the significant risks of worsening sub-arachnoid hemorrhage if anti-coagulation were to be used in the setting of percutaneous coronary intervention. The ST-segment elevations gradually resolved over the next 3 h. He remained hemo-dynamically stable and was successfully extubated 1 day after his cardiac arrest. With daily episodes of plasmapheresis his platelet count improved. After discussion with consultants from neurology and neurosurgery, aspirin 81 mg daily was initiated 8 days after the cardiac arrest. The patient was discharged home 12 days after admission with a platelet count of 244,000. His ADAMTS13 level, drawn at time of presentation, was undetectable, confirming the diagnosis of idiopathic TTP.
123
Four weeks after this event, with stable platelet counts and no cardiovascular symptoms, clopidogrel 75 mg daily was started, but a modest decline in platelet count led to discontinuation shortly after. He returned for elective stress myocardial perfusion imaging which demonstrated a large area of reversible ischemia in the territory of the left anterior descending artery (LAD). Coronary arteriography subsequently revealed a filling defect consistent with thrombus in the second diagonal branch (D2) of the LAD (Fig. 2). The patient was managed medically with continuation of aspirin. Three months after presentation, the patient is doing well, without residual neurological or cardiovascular symptoms. His platelet count is 138,000.
Discussion We report a case of a 56-year old man with TTP complicated by ST-elevation myocardial infarction treated with thrombolytic therapy. TTP is defined by the combination of microangiopathic hemolytic anemia and thrombocytopenia occurring in adults without an apparent alternative cause [6]. In cases of idiopathic TTP, a deficiency of the metalloprotease ADAMTS 13 results in failure to cleave von Willebrand factor multimers. The abnormally large multimers react with platelets to cause disseminated platelet clumping [7]. The resulting micro-vascular thrombosis can lead to renal failure and neurological symptoms. Macrovascular thrombosis is less common. Drug-induced TTP in the setting of clopidogrel is rare and generally manifests
ST-segment elevation myocardial infarction treated with thrombolytic therapy
Fig. 2 Arteriography of the left coronary artery demonstrating thrombus in the second diagonal branch (D2) of the left anterior descending artery (LAD)
after 2–14 days of clopidogrel therapy [8]. There is little evidence on the use of clopidogrel in patients with a history of idiopathic TTP [9]. For our patient, evidence of TTP was present prior to administration of clopidogrel. It is unknown if the re-initiation of clopidogrel and the subsequent decline in his platelet count were related. Prior case series have identified AMI as a clinically significant manifestation of TTP, with incidence ranging from 15 to 41 % [2–5]. Diagnosis is challenging. AMI may be under-recognized in this population due to lack of classic symptoms, poor reporting of symptoms resulting from impaired neurological status, or concern for other lifethreatening sequelae (bleeding, stroke, renal failure). AMI may result from micro-vascular thrombosis instead of epicardial coronary plaque rupture with thrombosis and occlusion. In a series of 14 patients with TTP and AMI, only three received coronary arteriography. Obstructive disease was seen in only one patient [4]. Additionally, treatment of AMI with appropriate anti-platelet and anticoagulant therapy is challenging in the setting of thrombocytopenia. The appropriate use and timing of antithrombotic medications in patients with TTP and AMI have not been studied. Angiography is often avoided due to risk of bleeding and an inability to use anti-platelet agents in the case of percutaneous coronary intervention. Renal insufficiency may limit use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Nonetheless, recent reports of mortality rates of 38 to 42 % [2, 4], much higher than in TTP patients without AMI,
underscore the need for prompt diagnosis and, when possible, treatment. Despite increasing recognition of AMI and the common autopsy findings of cardiac small vessel thrombosis [10, 11], ST-segment elevation MI in the setting of TTP remains rare. Our unusual case features chest pain as the only presenting symptom. It highlights the challenge of managing active myocardial infarction in the setting of TTP. Therapy for STEMI, including tenecteplase, was initiated prior to recognition of thrombocytopenia, a strategy that led to initial reperfusion but may have contributed to the subsequent sub-arachnoid hemorrhage. Discontinuation of anti-platelet and anti-coagulant therapy and/or the initiation of plasma exchange likely contributed to his reinfarction and cardiac arrest. We postulate that recurrent coronary thrombosis of his LAD led to his cardiac arrest and provoked the anterior ischemia on perfusion imaging. After partial resolution, this was visualized as a filling defect in his second diagonal branch on arteriography. Ultimately, we chose a conservative strategy of treatment of TTP followed by cautious re-initiation of aspirin therapy. Despite multiple complications, the patient recovered fully.
References 1. Hawkins BM et al (2008) Clinical cardiac involvement in thrombotic thrombocytopenic purpura: a systematic review. Transfusion 48(2):382–392 2. Gandhi K et al (2010) Cardiovascular manifestations in patients with thrombotic thrombocytopenic purpura: a single-center experience. Clin Cardiol 33(4):213–216 3. McCarthy LJ et al (2002) Myocardial infarction/injury is relatively common at presentation of acute thrombotic thrombocytopenic purpura: the Indiana University experience. Ther Apher 6(1):2–4 4. Patschan D et al (2006) Acute myocardial infarction in thrombotic microangiopathies—clinical characteristics, risk factors and outcome. Nephrol Dial Transplant 21(6):1549–1554 5. Wahla AS et al (2008) Myocardial infarction in thrombotic thrombocytopenic purpura: a single-center experience and literature review. Eur J Haematol 81(4):311–316 6. George JN (2006) Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 354(18):1927–1935 7. Moake JL (2002) Thrombotic microangiopathies. N Engl J Med 347(8):589–600 8. Bennett CL et al (2000) Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 342(24):1773–1777 9. Lotta LA et al (2012) Case report: use of thienopyridines in a patient with acquired idiopathic thrombotic thrombocytopenic purpura. J Thromb Thrombolysis 34(3):416–418 10. Podolsky SH et al (1999) Massive myocardial necrosis in thrombotic thrombocytopenic purpura: a case report and review of the literature. Arch Pathol Lab Med 123(10):937–940 11. Ridolfi RL, Bell WR (1981) Thrombotic thrombocytopenic purpura. Report of 25 cases and review of the literature. Medicine (Baltimore) 60(6):413–428
123
ST-segment elevation myocardial infarction treated with thrombolytic therapy in a patient with thrombotic thrombocytopenic purpura Jacob A. Doll • Jacob P. Kelly
Ó Springer Science+Business Media New York 2013
Abstract Acute myocardial infarction is a common complication of thrombotic thrombocytopenic purpura (TTP), but rarely the presenting manifestation. Antithrombotic therapy for myocardial infarction is rarely utilized in the setting of TTP because of elevated bleeding risk. We report a case of TTP presenting with ST-segment elevation myocardial infarction and treated with thrombolytic therapy. The resultant cardiac and neurological complications highlight the challenges of using evidence-based therapy for myocardial infarction in the setting of TTP. Keywords Myocardial infarction Thrombotic thrombocytopenic purpura Thrombolytic therapy
Introduction Cardiovascular complications of thrombotic thrombocytopenic purpura (TTP) are common and likely under-recognized [1]. Several case reports and small case series have documented myocardial infarction in the setting of TTP, but there is scant data on the course of disease in these patients [2–5]. Rarely, acute myocardial infarction (AMI) may be the presenting manifestation. Treatment of these patients is complicated by conflicting strategies for management of TTP and AMI. We report a case of TTP presenting with ST-segment elevation myocardial infarction (STEMI) and treated with thrombolytic therapy, with subsequent cardiac and neurological complications.
J. A. Doll (&) J. P. Kelly Duke University Medical Center, 2301 Erwin Road, DUMC 3845, Durham, NC 27710, USA e-mail: [email protected]
Case report A 56-year-old Caucasian man presented to a community hospital with complaint of 30 min of severe, sub-sternal chest pain radiating to his left shoulder. Prior to this episode, the patient was in his usual state of excellent health without known medical problems or risk factors for coronary artery disease. An ECG obtained at presentation demonstrated STsegment elevations in leads I and aVL with reciprocal STsegment depressions in leads II, III, and aVF. The acute myocardial infarction protocol was activated. The patient received 325 mg of aspirin, 600 mg of clopidogrel, a weight-based loading dose of heparin, morphine, and sublingual nitroglycerine without resolution of symptoms. Due to lack of cardiac catheterization facilities at the hospital, the patient then received 50 mg of intravenous tenecteplase and was transferred immediately to our hospital for further management and consideration of rescue percutaneous coronary intervention. On arrival to our hospital the patient was free of chest pain, and repeat ECG showed partial ([50 %) resolution of ST-segment elevations. He therefore met criteria for successful thrombolysis and immediate rescue cardiac catheterization was not performed. A complete blood count drawn on arrival was notable for a platelet count of 38,000. A platelet count from the referring hospital, drawn but not resulted prior to the administration of tenecteplase, clopidogrel, and aspirin, was 40,000. This thrombocytopenia prompted a concern for TTP. A blood smear was prepared which showed 3–5 schistocytes per high power field. Other classic signs of TTP, including altered mental status, fever, and renal dysfunction, were absent. However, no other etiology of micro-angiopathic hemolytic anemia was identified, and a diagnosis of TTP was made. Therapy with
123
J. A. Doll, J. P. Kelly
Fig. 1 12-lead electrocardiogram performed after resuscitation from cardiac arrest
corticosteroids and plasma exchange was initiated. All anticoagulant and anti-platelet medications were discontinued and cardiac catheterization was deferred. Echocardiography performed the morning of admission demonstrated an ejection fraction of 40 % with apical and antero-lateral hypokinesis. During the second round of plasma exchange, performed 1 day after admission, the patient had an abrupt worsening of mental status and suffered a cardiac arrest with pulseless electrical activity. With cardiopulmonary resuscitation he developed ventricular fibrillation, which was successfully defibrillated. The patient was intubated in the course of the resuscitation. A post-resuscitation ECG was notable for anterior and lateral ST-segment elevations (Fig. 1). A noncontrast CT scan of the head demonstrated a small subarachnoid hemorrhage in the right frontal lobe. Coronary angiography was deferred, due to the significant risks of worsening sub-arachnoid hemorrhage if anti-coagulation were to be used in the setting of percutaneous coronary intervention. The ST-segment elevations gradually resolved over the next 3 h. He remained hemo-dynamically stable and was successfully extubated 1 day after his cardiac arrest. With daily episodes of plasmapheresis his platelet count improved. After discussion with consultants from neurology and neurosurgery, aspirin 81 mg daily was initiated 8 days after the cardiac arrest. The patient was discharged home 12 days after admission with a platelet count of 244,000. His ADAMTS13 level, drawn at time of presentation, was undetectable, confirming the diagnosis of idiopathic TTP.
123
Four weeks after this event, with stable platelet counts and no cardiovascular symptoms, clopidogrel 75 mg daily was started, but a modest decline in platelet count led to discontinuation shortly after. He returned for elective stress myocardial perfusion imaging which demonstrated a large area of reversible ischemia in the territory of the left anterior descending artery (LAD). Coronary arteriography subsequently revealed a filling defect consistent with thrombus in the second diagonal branch (D2) of the LAD (Fig. 2). The patient was managed medically with continuation of aspirin. Three months after presentation, the patient is doing well, without residual neurological or cardiovascular symptoms. His platelet count is 138,000.
Discussion We report a case of a 56-year old man with TTP complicated by ST-elevation myocardial infarction treated with thrombolytic therapy. TTP is defined by the combination of microangiopathic hemolytic anemia and thrombocytopenia occurring in adults without an apparent alternative cause [6]. In cases of idiopathic TTP, a deficiency of the metalloprotease ADAMTS 13 results in failure to cleave von Willebrand factor multimers. The abnormally large multimers react with platelets to cause disseminated platelet clumping [7]. The resulting micro-vascular thrombosis can lead to renal failure and neurological symptoms. Macrovascular thrombosis is less common. Drug-induced TTP in the setting of clopidogrel is rare and generally manifests
ST-segment elevation myocardial infarction treated with thrombolytic therapy
Fig. 2 Arteriography of the left coronary artery demonstrating thrombus in the second diagonal branch (D2) of the left anterior descending artery (LAD)
after 2–14 days of clopidogrel therapy [8]. There is little evidence on the use of clopidogrel in patients with a history of idiopathic TTP [9]. For our patient, evidence of TTP was present prior to administration of clopidogrel. It is unknown if the re-initiation of clopidogrel and the subsequent decline in his platelet count were related. Prior case series have identified AMI as a clinically significant manifestation of TTP, with incidence ranging from 15 to 41 % [2–5]. Diagnosis is challenging. AMI may be under-recognized in this population due to lack of classic symptoms, poor reporting of symptoms resulting from impaired neurological status, or concern for other lifethreatening sequelae (bleeding, stroke, renal failure). AMI may result from micro-vascular thrombosis instead of epicardial coronary plaque rupture with thrombosis and occlusion. In a series of 14 patients with TTP and AMI, only three received coronary arteriography. Obstructive disease was seen in only one patient [4]. Additionally, treatment of AMI with appropriate anti-platelet and anticoagulant therapy is challenging in the setting of thrombocytopenia. The appropriate use and timing of antithrombotic medications in patients with TTP and AMI have not been studied. Angiography is often avoided due to risk of bleeding and an inability to use anti-platelet agents in the case of percutaneous coronary intervention. Renal insufficiency may limit use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Nonetheless, recent reports of mortality rates of 38 to 42 % [2, 4], much higher than in TTP patients without AMI,
underscore the need for prompt diagnosis and, when possible, treatment. Despite increasing recognition of AMI and the common autopsy findings of cardiac small vessel thrombosis [10, 11], ST-segment elevation MI in the setting of TTP remains rare. Our unusual case features chest pain as the only presenting symptom. It highlights the challenge of managing active myocardial infarction in the setting of TTP. Therapy for STEMI, including tenecteplase, was initiated prior to recognition of thrombocytopenia, a strategy that led to initial reperfusion but may have contributed to the subsequent sub-arachnoid hemorrhage. Discontinuation of anti-platelet and anti-coagulant therapy and/or the initiation of plasma exchange likely contributed to his reinfarction and cardiac arrest. We postulate that recurrent coronary thrombosis of his LAD led to his cardiac arrest and provoked the anterior ischemia on perfusion imaging. After partial resolution, this was visualized as a filling defect in his second diagonal branch on arteriography. Ultimately, we chose a conservative strategy of treatment of TTP followed by cautious re-initiation of aspirin therapy. Despite multiple complications, the patient recovered fully.
References 1. Hawkins BM et al (2008) Clinical cardiac involvement in thrombotic thrombocytopenic purpura: a systematic review. Transfusion 48(2):382–392 2. Gandhi K et al (2010) Cardiovascular manifestations in patients with thrombotic thrombocytopenic purpura: a single-center experience. Clin Cardiol 33(4):213–216 3. McCarthy LJ et al (2002) Myocardial infarction/injury is relatively common at presentation of acute thrombotic thrombocytopenic purpura: the Indiana University experience. Ther Apher 6(1):2–4 4. Patschan D et al (2006) Acute myocardial infarction in thrombotic microangiopathies—clinical characteristics, risk factors and outcome. Nephrol Dial Transplant 21(6):1549–1554 5. Wahla AS et al (2008) Myocardial infarction in thrombotic thrombocytopenic purpura: a single-center experience and literature review. Eur J Haematol 81(4):311–316 6. George JN (2006) Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 354(18):1927–1935 7. Moake JL (2002) Thrombotic microangiopathies. N Engl J Med 347(8):589–600 8. Bennett CL et al (2000) Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 342(24):1773–1777 9. Lotta LA et al (2012) Case report: use of thienopyridines in a patient with acquired idiopathic thrombotic thrombocytopenic purpura. J Thromb Thrombolysis 34(3):416–418 10. Podolsky SH et al (1999) Massive myocardial necrosis in thrombotic thrombocytopenic purpura: a case report and review of the literature. Arch Pathol Lab Med 123(10):937–940 11. Ridolfi RL, Bell WR (1981) Thrombotic thrombocytopenic purpura. Report of 25 cases and review of the literature. Medicine (Baltimore) 60(6):413–428
123
