Tenecteplase for ST-elevation myocardial infarction in a patient treated with drotrecogin alfa (activated) for severe sepsis: a case report

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Drotrecogin alfa (activated) (DrotAA), an activated protein C, promotes fibrinolysis in patients with severe sepsis. There are no reported cases or studies that address the diagnosis and treatment of myocardial infarction in septic patients treated with DrotAA.

Case presentation
A 59-year-old Caucasian man with septic shock secondary to community-acquired pneumonia treated with DrotAA, subsequently developed an ST-elevation myocardial infarction 12 hours after starting DrotAA. DrotAA was stopped and the patient was given tenecteplase thrombolysis resulting in complete resolution of ST-elevation and no adverse bleeding events. DrotAA was restarted to complete the 96-hour course. The sepsis resolved and the patient was discharged from hospital.

In patients with severe sepsis or septic shock complicated by myocardial infarction, it is difficult to determine if the myocardial infarction is an isolated event or caused by the sepsis process. The efficacy and safety of tenecteplase thrombolysis in septic patients treated with DrotAA need further study.


Sepsis with multi-organ failure has a high incidence and a mortality rate of 30-50% [1]. The pathophysiology of sepsis is an inflammatory and procoagulant state triggered by infection. Activated protein C (APC) plays an important role by promoting fibrinolysis and inhibiting thrombosis and inflammation. The PROWESS trial reported a 6.1% absolute reduction in 28-day mortality for septic patients treated with drotrecogin alfa (activated) (DrotAA) [2]. Subsequent studies and subanalyses have suggested that most of the benefit is seen in patients with high illness severity scores or multiple organ dysfunction [3]. In our center, patients are treated with DrotAA (24 mcg/kg/hour ─éÔÇö 96 hours) when there is evidence of infection, signs of systemic inflammatory response syndrome plus two or more organ system failures or one organ system failure and APACHE II score ├óÔÇ░─ä25. Patients are excluded if death is perceived to be imminent, sepsis-induced organ failure has lasted more than 48 hours or there is an increased risk of life-threatening or intracranial bleeding.

Case presentation
A 59-year-old Caucasian man presented to the emergency department after a motor vehicle collision and was found to have a right lower lobe pneumonia but no other injuries. He was discharged home on azithromycin. He had a history of type 2 diabetes, asthma, hypertension and hyperlipidemia, but he was a non-smoker with a negative history for coronary heart disease or strokes. His medication included ventolin, glyburide, metformin, quinipril, atorvastatin and aspirin. Two days later, he presented to the same emergency department with a decreased level of consciousness and respiratory distress, requiring mechanical ventilation and transfer to the intensive care unit (ICU).

On admission, he was hemodynamically stable and his temperature was 39.2├é┬░C. His white blood cell count was 11.3 ─éÔÇö 109/L, hemoglobin 131 g/L and platelets 150 ─éÔÇö 109/L. Arterial blood gas showed a PaO2 97 mmHg on 100% oxygen, PaCO2 54 mmHg, bicarbonate 25 mmol/L and pH 7.32. His lactate level was 2.1 mmol/L, SvO2 76% and troponin I was elevated at 0.6 ├Ä─¢g/L. His international normalized ratio (INR), partial thromboplastin time (PTT), liver enzymes and electrolytes were normal, but creatinine was elevated at 211 ├Ä─¢mmol/L. His chest X-ray demonstrated worsening of pneumonia and his electrocardiogram (ECG) showed no evidence of ischemia. Intravenous antibiotics (cefotaxime) were given pending microbiological culture results.

Four hours after presentation, his mean arterial pressure (MAP) decreased from 77 mmHg to 60 mmHg and he was unresponsive to fluid resuscitation alone. There were no ischemic changes on ECG monitoring and further troponin I testing was not performed. The rest of the laboratory tests were unchanged. It was felt that the patient had developed severe sepsis secondary to community-acquired pneumonia and norepinephrine plus vasopressin (0.4 U/minute) were initiated for blood pressure support. His APACHE score was 26, and with two dysfunctional organs, DrotAA and hydrocortisone were initiated as part of severe sepsis treatment.


  1. Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP: The natural history of the systemic inflammatory response syndrome (SIRS): a prospective study. JAMA 1995, 273:117-123.
  2. Bernard GR, Vincent J, Laterre P, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher C: Efficacy and safety of recombinant Activated Protein C for severe sepsis. N Engl J Med 2001, 344:699-709.
  3. Wiedermann CJ, Kaneider NC: A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis. BMC Emerg Med 2005, 5:7.
  4. Krishnagopalan S, Kumar A, Parrillo JE, Kumar A: Myocardial dysfunction in the patient with sepsis. Curr Opin Crit Care 2002, 8:376-388.
  5. Ammann P, Maggiorini M, Bertel O, Haenseler E, Joller-Jemelka HI, Oechslin E, Minder EI, Rickli H, Fehr T: Troponin as risk factor for mortality in critically ill patients without acute coronary syndromes. J Am Coll Cardiol 2003, 41:2004-2009.
  6. Terradellas JB, Bellot JF, Saris AB, Gil CL, Torrallardona AT, Garriga JR: Acute and transient ST segment elevation during bacterial shock in seven patients without apparent heart disease. Chest 1982, 81:444-448.
  7. Relos RP, Hasinoff IK, Beilman GJ: Moderately elevated serum troponin concentrations are associated with increased morbidity and mortality rates in surgical intensive care unit patients. Crit Care Med 2003, 31:2598-2603.
  8. Holmes CL, Walley KR, Chittock DR, Lehman T, Russell JA: The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series. Intensive Care Med 2001, 27:1416-1421.
  9. Hashimoto M, Yamashita T, Oiwa K, Watanabe S, Giddings JC, Yamamoto J: Enhancement of endogenous plasminogen activator- induced thrombolysis by argatroban and APC and its control by TAFI, measured in an arterial thrombolysis model in vivo using rat mesenteric arterioles. Thromb Haemost 2002, 87:110-113.
  10. Sakamoto T, Ogawa H, Yasue H, Oda Y, Kitajima S, Tsumoto K, Mizokami H: Prevention of arterial reocclusion after thrombolysis with activated protein C: Comparison with heparin in a canine model of coronary artery thrombosis. Circulation 1994, 90:427-432.
  11. Sakamoto T, Ogawa H, Takazoe K, Yoshimura M, Shimomura H, Moriyama Y, Arai H, Okajima K: Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase. J Am Coll Cardiol 2003, 42:1389-1394.
  12. Prasa A, Lerman A, Rihal CS: Apical ballooning syndrome (Tako- Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction). Am Heart J 2007, 155:408-416.
  13. Geng S, Mullany D, Fraser JF: Takotsubo cardiomyopathy associated with sepsis due to Streptococcus pneumoniae pneumonia. Crit Care Resusc 2008, 10:231-234.