Cardiac Injury Is a Common Postmortem Finding in Thrombotic Thrombocytopenic Purpura Patients: Is Empiric Cardiac Monitoring and Protection Needed?

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal disease. Early implementation of therapeutic plasma exchange (TPE) has decreased the mortality rate from >90% to <10%. However, fatalities still occur in these patients. The goal of this study was to characterize the causes of death and related postmortem findings in patients with TTP in the current era of emergent TPE to identify possible areas for improvement in the care of these patients. We analyzed clinical history, laboratory and histopathologic findings, and causes of death of patients with active TTP or TTP in clinical remission autopsied at our institution over 22 years. Of 18 patients, 15 had TTP judged to be a cause of death: it was an underlying cause of death in five cases, intermediate in three, and contributing in seven. The most common immediate causes of death were cardiac arrest and myocardial infarction. The most common TTP-related findings at autopsy were thrombi/emboli in heart (9), lung (11), brain (3), kidney (7), followed by hemorrhages in heart (7), lung (8), brain (2), kidney (7), and infarcts in heart (5), lung (4), brain (6) and kidney (3). Analysis of the cases with TTP as a cause of death suggests that the mechanism of death is commonly cardiac in origin. Proactive measures to monitor and protect the heart may be beneficial in these patients.

Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura

“…Our experimental results are in line with increasing evidence suggesting that heart involvement is a frequent feature in TTP [39], and is responsible for a high mortality rate [14,20,37]. Alteration of systolic function in our model remains moderate and transient, in agreement with with the low proportion of congestive heart failure in humans [20].…”

“…Therefore, these myocardial perfusion alterations may contribute to alterations in cardiac function and structure, as previously reported by our group [29]. Moreover, our macroscopic and histologic observations of hearts isolated from rhVWF-treated ADAMTS-13 KO mice are consistent with the microvascular effects observed in TTP patients [37], in other animal models of induced TTP [38], and in the initial model, in which the heart was identified as a sensitive target organ with a multifocal distribution pattern of myocardial necrosis and hemorrhage associated with hyaline thrombi [7].…”

Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura

“…The platelet count is the generally accepted indicator of disease activity in acquired TTP and guides treatment decisions such as when to stop daily plasma exchange. 11 Symptoms of acquired TTP vary according to the organs affected by the tissue ischemia, 17 reflecting cardiac, 4,5,[18][19][20][21] neurologic, 22 or renal 18,23 injury. The pathogenesis of acquired TTP is mediated by the production of autoantibodies against ADAMTS13, the key factor controlling von Willebrand factor-mediated platelet aggregation, and these autoantibodies are the focus of current treatment.…”

“…2 Decreased ADAMTS13 activity leads to an accumulation of ultralarge von Willebrand factor multimers, which bind to platelets and induce aggregation. 3 These microthrombi cause tissue ischemia and organ dysfunction (commonly involving the brain, heart, and kidneys), resulting in early death 4,5 or in long-term complications, such as cognitive deficits, depression, and arterial hypertension, and a shortened life expectancy. [6][7][8][9][10] Treatment of acquired TTP consists of rapid initiation of plasma exchange to remove autoantibodies and ultralarge von Willebrand factor multimers and to replenish ADAMTS13.…”

Thrombotic thrombocytopenic purpura

“…Organ involvement of TTP is also highly variable and can imply any organ, leading to various initial presentations. Clinical and biological anomalies that may be present on diagnosis of TTP are summarized in Table 1 [12][13][14][15][16][17]. Cardiac involvement must systematically be searched because of its association with increased mortality rate and refractory forms of TTP [10 & ].…”