Outcomes in 1096 patients with severe thrombotic thrombocytopenic purpura before the Caplacizumab era

Abstract

Introduction Thrombotic thrombocytopenic purpura (TTP) is a diagnostic and therapeutic emergency. Therapeutic plasma exchange (TPE) combined with immunosuppression has been the cornerstone of the initial management. To produce optimal benefits, emerging treatments must be used against a background of best standard of care. Clarifying current uncertainties is therefore crucial. Methods The objective of this study was to analyze a large high-quality database (Marketscan) of TTP patients managed between 2005 and 2014, in the pre-caplacizumab era, in order to assess the impact of time to first TPE and use of first-line rituximab on mortality, and whether mortality declines over time. Results Among the 1096 included patients (median age 46 [IQR 35–55], 70% female), 28.8% received TPE before day 2 in the ICU. Hospital mortality was 7.6% (83 deaths). Mortality was independently associated with older age (hazard ratio [HR], 1.024/year; 95% confidence interval [95%CI], [1.009–1.040]), diagnosis of sepsis (HR, 2.360; 95%CI [1.552–3.588]), and the need for mechanical ventilation (HR, 4.103; 95%CI, [2.749–6.126]). Factors independently associated with lower mortality were TPE at ICU admission (HR, 0.284; 95%CI, [0.112–0.717]), TPE within one day after ICU admission (HR, 0.449; 95%CI, [0.275–0.907]), and early rituximab therapy (HR, 0.229; 95% CI, [0.111–0.471]). Delayed TPE was associated with significantly higher costs. Conclusions Immediate TPE and early rituximab are associated with improved survival in TTP patients. Improved treatments have led to a decline in mortality over time, and alternate outcome variables such as the use of hospital resources or longer term outcomes therefore need to be considered.

Severe Thrombotic Thrombocytopenic Purpura (TTP) with Organ Failure in Critically Ill Patients

“…The most recently published (2021) multicenter study of patients with TTP, ICU admitted or otherwise, shows that, out of 1096 patients, only 314 (28.6%) had neurological signs. In this large study, the presence of neurological signs was not associated with mortality [14]. Mirouse and colleagues have published findings from the largest retrospective cohort of neurological manifestations in patients with TTP admitted to the ICU, from which, 108 out of 130 (83%) patients with TTP exhibited neurological symptoms over a 12-year period [30].…”

“…Considering the rare incidence of TTP, experts recommend that patients should preferably be admitted to a referral center with a multidisciplinary team experienced in the management of TTP in intensive and long-term care that includes, at the least, a TTP specialist, a hematologist and an intensivist [11,12]. Various studies show that ICU admission varies between 40% and 100% of patients with TTP, either because of severe organ failure or in order to initiate emergency plasma exchange (PEx), 7 days a week, 24 h a day [13,14]. In ICUs, data on the use of life-sustaining therapy are very scarce.…”

“…In a population of 1096 patients with TTP admitted to the ICU, 17% required one life-sustaining therapy, and 3% required two or more life-preserving therapies, respectively. In total, 9% required mechanical ventilation, 16% required renal replacement therapy (RRT) and 0.6% needed vasopressor therapy [14]. Morbid obesity has been suggested as a risk factor for severe TTP, with an increased risk of cardiovascular and renal complications [15,16].…”

“…Transthoracic echocardiography was available in 56 patients and revealed left ventricular dysfunction in 9 patients (16.1%), focal hypokinesia in 11 patients (19.6%) and pericardial effusion in 12 (21.4%) [48]. In 2021, Van de Louw et al reported a prevalence of 0.6% (n = 7) for cardiogenic shock and 5% (n = 56) for myocardial infarction in a cohort of 1096 patients [14]. The presence of microvascular cardiac damage, frequent in TTP, and its association in various studies with higher mortality, has raised the question of adjuvant therapy such as anti-platelet aggregation treatment.…”

“…PEx with replacement of plasma remains the cornerstone of the current management of TTP and should be started as soon as the diagnosis of TTP is suspected. The risk of death is maximal before PEx is initiated [14]. Experts recommend a daily PEx with a plasma dose of 60 mL/kg (1.5 × estimated plasma volume) until the platelet count is above 150 G/L for 48 h [68].…”