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 .
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 . Takotsubo has been described with Streptococcus pneumoniae infections, as seen in this patient . 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.
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