Cardiac implications of thrombotic thrombocytopenic purpura

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder that essentially can affect any organ in the human body. The hallmark of the pathogenesis in TTP is the large von Willebrand factor multimers on platelet-mediated micro-thrombi formation, leading to microvascular thrombosis. Autopsy studies showed that cardiac arrest and myocardial infarction are the most common immediate causes of death in these patients. Clinical manifestations of cardiac involvement in TTP vary dramatically, from asymptomatic elevation of cardiac biomarkers, to heart failure, MI and sudden cardiac death. There is limited knowledge about optimal cardiac evaluation and management in patients with TTP. The absence of typical cardiac symptoms, combined with complicated multi-organ involvement in TTP, may contribute to the under-utilization of cardiac evaluation and treatment. Prompt diagnosis and timely initiation of effective therapy could be critically important in selected cases. Based on our experience and this review of the literature, we developed several recommendations for focused cardiac evaluation for patients with acute TTP: (1) patients with suspected or confirmed TTP should be screened for the potential presence of cardiac involvement with detailed history and physical, electrocardiogram and cardiac enzymes; (2) clinical deterioration of TTP patients warrants immediate cardiac reevaluation; (3) TTP patients with clinical evidence of cardiac involvement should be monitored for telemetry, cardiac biomarkers and evaluated with transthoracic echocardiography. These patients require urgent targeted TTP treatment as well as cardiac-specific treatment. Aspirin therapy is indicated for all TTP patients. Since epicardial coronary artery involvement is rare, cardiac catheterization is usually not required, given the high risk for hemorrhage and kidney injury; (4) we recommend evidence-based medical therapy for ischemic symptoms and heart failure. TTP patients with evidence of cardiac involvement would also benefit from routine cardiology follow up during remission.

Keywords: Thrombotic thrombocytopenic purpura; Acute myocardial infarction; Coronary artery disease; Anti-platelet therapy; von Willebrand factor; ADAMTS13

Core tip: Thrombotic thrombocytopenic purpura (TTP) is a grave medical condition caused by the formation of von Willebrand factor multimers that cause large platelet plugs and diffuse microemboli, leading to life-threatening, multi-organ ischemic injuries. Although cardiac involvement commonly occurs related to TTP, these cardiac manifestations have not been well studied and may thus be overlooked in clinical practice. Management of cardiac ischemia or myocardial infarction in TTP is also challenging due to increased hemorrhagic risk in the setting of thrombocytopenia. In this report, we systematically review available clinical data in the literature and summarize clinical manifestation, diagnostic workup strategies, prognosis, and the outcomes of cardiac involvement of TTP. We provide recommendations on the strategies for clinical assessment and management of TTP patients with cardiac involvement.