Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS): a 24-year clinical experience with 178 patients

Mark Levandovsky,Danielle Harvey,Ted Wun,Primo Lara

doi:10.1186/1756-8722-1-23

Abstract

BackgroundThrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTP-HUS) are related and uncommon disorders with a high fatality and complication rate if untreated. Plasma exchange therapy has been shown to produce high response rates and improve survival in patients with many forms of TTP-HUS. We performed a retrospective cohort study of 178 consecutively treated patients with TTP-HUS and analyzed whether clinical or laboratory characteristics could predict for important short- and long-term outcome measures.ResultsOverall 30-day mortality was 16% (n = 27). 171 patients (96%) received plasma exchange as the principal treatment, with a mean of 8 exchanges and a mean cumulative infused volume of 42 ± 71 L of fresh frozen plasma. The rate of complete response was 65% or 55% depending on whether this was defined by a platelet count of 100,000/μl or 150,000/μl, respectively. The rate of relapse was 18%. The Clinical Severity Score did not predict for 30-day mortality or relapse. The time to complete response did not predict for relapse. Renal insufficiency at presentation was associated with a decreased risk of relapse, with each unit increase in serum creatinine associated with a 40% decreased odds of relapse. 72% of our cohort had an idiopathic TTP-sporadic HUS, while 17% had an underlying cancer, received a solid organ transplant or were treated with a mitomycin-based therapy. The estimated overall 5-year survival was 55% and was significantly better in those without serious underlying conditions.ConclusionPlasma exchange therapy produced both high response and survival rates in this large cohort of patients with TTP-HUS. The Clinical Severity Score did not predict for 30-day mortality or relapse, contrary to our previous findings. Interestingly, the presence of renal insufficiency was associated with a decreased risk of relapse. The most important predictor of mortality was the presence or absence of a serious underlying disorder.

Highlights

Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTPHUS) are related and uncommon disorders with a high fatality and complication rate if untreated
Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome are rare, closely-related disorders characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia
First described by Gasser et al in 1955[6], is often preceded by a diarrheal illness and presents with MAHA and thrombocytopenia and a clinical picture dominated by renal insufficiency

Summary

Introduction

Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTPHUS) are related and uncommon disorders with a high fatality and complication rate if untreated. Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome are rare, closely-related disorders characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. The presence of ULVWF was found to be due to a lack of von Willebrand cleaving protease activity, due either to congenital deficiency or an IgG inhibitor [8,9,10]. This protease has been identified[11,12] and designated ADAMTS13 (A disintegrin and metalloproteinase family with thrombospondin-like motifs) and processes the ULVWF by proteolytic cleavage. Pathologic differences have been observed between malignancy and chemotherapy associated TTP-HUS as compared to idiopathic/HIV-linked TTP and sporadic HUS [13,14]; the former characterized by both micro and macrovascular fibrin thrombi, as opposed to the microvascular, platelet-rich angiopathy seen in the latter

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