Figure 1.
Clinical and imaging data highlighting manifestations of ponatinib-mediated coronary thrombotic microangiopathy. (A) Temporal trends for WBC count (red triangles) and serum troponin I (green circles) relative to the timing of leukapheresis (LA), echocardiography with MCE (dashed lines), and initiation of NAC (shaded area extending to 2 half-lives after last dose). (B) Transthoracic echocardiography demonstrating left ventricular endocardial and epicardial borders (dashed lines) in the midventricular parasternal short-axis plane on noncontrast 2-dimensional imaging and a schematic showing cardiac orientation with gray region overlying the anterolateral region where perfusion was abnormal (upper panels) and corresponding MCE perfusion imaging (bottom panels) prior to NAC treatment with a tissue-subtraction algorithm whereby opacification occurs only where microbubble contrast agent is present, demonstrating patchy regions lacking perfusion (arrows) in the anterolateral region. The bright central region represents the opacified ventricular cavity. The color-coded image is provided to highlight regions lacking perfusion within the confines of the left ventricular borders. (C) Lead I and V6 tracings from ECGs performed on initial presentation, after leukapheresis and approximately 24 hours after initiation of NAC (see supplemental Figure 1 for the full 12-lead ECG on presentation). (D) Postmortem immunohistochemistry for platelet CD61 (β3-integrin) and corresponding hematoxylin and eosin staining showing evidence recent platelet-rich microvascular thrombus and mural hyperplasia involving arterioles. Brown indicates secondary peroxidase staining.