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

Login or register to view PDF.


APC inhibits coagulation by inactivating factor Va and VIIIa and promotes fibrinolysis by inhibition of type 1 plasminogen activator inhibitor (PAI-1). Animal models suggest that APC enhances thrombolysis and prevents re-occlusion in coronary artery thrombosis [9,10]. A small randomized controlled trial investigating the addition of DrotAA versus unfractionated intravenous heparin with tissue plasminogen activator in patients with ST-elevation myocardial infarction (STEMI) found that the DrotAA group had lower levels of PAI-1. The authors concluded that DrotAA may be beneficial in the treatment of acute myocardial infarction, however the study lacked clinical outcomes and thenumbers were too small to make any meaningful conclusion regarding the use of DrotAA in STEMI or for prevention of thrombotic events [11].

To the best of our knowledge, our patient is the first reported case of severe sepsis treated with TNK while on DrotAA for STEMI. The differential diagnosis includes streptococcal myocarditis and stress-induced Takotsubo cardiomyopathy with clinical presentations indistinguishable from myocardial infarction. For patients with myocarditis, a definitive diagnosis cannot be made without tissue biopsy and cultures. Takotsubo cardiomyopathy will typically have ST-elevation in the precordial leads, mild to modest elevations in cardiac troponins, hypokinesis of the mid to apical segments of the left ventricle and no critical lesions on cardiac angiogram [12]. Takotsubo has been described with Streptococcus pneumoniae infections, as seen in this patient [13]. However, our patient had an inferolateral distribution of ischemia with a marked elevation in troponin I and global hypokinesis, which is atypical for Takotsubo cardiomyopathy.

Our patient with severe sepsis was found to have ST-elevations on ECG, a large troponin rise and global cardiac hypokinesis. Given that our center did not have access to urgent cardiac catheterization, we elected to treat him as a STEMI patient with the accepted standard of TNK thrombolysis followed by heparin infusion. DrotAA was stopped because of the increased risk of bleeding and then resumed for ongoing sepsis 8 hours after the thrombolysis. The patient had resolution of ST-elevations post-thrombolysis with improvement in cardiac function as well as resolution of sepsis with no adverse bleeding events.

A cardiac angiogram performed post-thrombolysis revealed mild irregularities and no coronary artery occlusion, suggesting a non-thrombotic cause for his cardiac event. However, the findings could also reflect successful thrombolysis. This is supported by evidence of osterolateral and inferior wall hypokinesis with left circumflex artery irregularity, corresponding to the initial ECG ST-elevation territory. The global hypokinesis seen on echocardiogram before cardiac catheterization may have been due to a combination of sepsis-induced myocardial dysfunction and a possible ischemic event. Unfortunately, without primary cardiac catheterization, we cannot definitively know whether our patient's cardiac dysfunction was secondary to a thrombotic mechanism versus induced by sepsis.


  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.