Focus on Key Issues in Immune Thrombotic Thrombocytopenic Purpura: Italian Experience of Six Centers.

Giovanni Tiscia,Elvira Grandone,Teresa Maria Santeramo,Gaetano Giuffrida,Anna Cerbo,Elena Chinni,Lorella Melillo,Antonella Bertomoro,Angelo Ostuni,Giulio Giordano,Fabrizio Fabris,Lucia Fischetti,Maria Teresa Sartori,Giuseppe Tarantini,Nicola Cascavilla,Daniela Nicolosi,Filomena Cappucci,Cosima Battista

doi:10.3390/jcm10235702

Abstract

Immune-mediated thrombotic thrombocytopenic purpura is a rare and challenging hematological disease caused by the antibody anti-ADAMTS13. Though the mortality rate has decreased considerably in recent years, fatalities still remain unacceptable. This study aimed at further adding to the existing knowledge of this medical challenge. We enrolled 89 consecutive patients observed in six Italian centers (from 8 August 2013 to 28 May 2021) with a diagnosis of immune-mediated thrombotic thrombocytopenic purpura. Clinical information and blood parameters were collected for all patients. We describe clinical manifestations and laboratory data, possible risk factors and the therapeutic management of first episodes or relapses. A total of 74 first episodes and 19 relapses (median 3 years (interquartile range (IQR): 2–7)) were recorded. Seventy percent of patients enrolled at the first episode showed neurological signs and/or symptoms. All the patients enrolled at the first episode were treated with plasma exchange (median = 12; IQR: 8–19.5) and methylprednisolone (1 mg/kg/day). Rituximab (375 mg/m2 weekly for four weeks) and caplacizumab were given to 15 (20.2%) and 2 patients (2.6%), respectively. We observed an overall mortality of 5.4% in the follow-up (median 60 months; IQR: 36.0–103.5). All fatalities occurred after a diagnostic delay. Present data point to the importance of the early detection of factors mostly associated with poor outcomes. It is likely that use of caplacizumab could improve the prognosis in those patients.

Highlights

Thrombotic thrombocytopenic purpura (TTP) is a rare hematological disease
We categorized clinical and laboratory manifestations according to the specific physiopathological features of immune-mediated TTP (iTTP), paying specific attention to thrombocytopenia, neurological, bleeding-related cardiac, renal and gastrointestinal signs and symptoms [10]
We describe a series of iTTP cases recruited in six Italian centers during a wide frame of time

Summary

Introduction

Thrombotic thrombocytopenic purpura (TTP) is a rare hematological disease. It is one of the thrombotic microangiopathies (TMAs) characterized by thrombocytopenia, hemolytic anemia and thrombosis in micro-vessels [1]. At the beginning of the 1980, Moake et al published the first evidence of TTP pathophysiology [2]. They observed that patients with relapsing TTP can show a significant blood accumulation of ultra-large multimers of the von Willebrand factor (VWF)—a platelet adhesive protein. A severe ADAMTS13 deficiency (defined as protease activity below 10% of normal or 10 U/dL), due to mutations within ADAMTS13 gene or specific anti-ADAMTS13 auto-antibodies, induces congenital TTP or immune-mediated TTP (iTTP), respectively [3,4,5,6]. Epidemiological data show that immune-mediated cases account for approximately 95% of all the TTP diagnoses with an incidence rate of 1/250,000 to

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