Thrombotic thrombocytopenic purpura.

Kremer Hovinga JA; Coppo P; Lämmle B; Moake JL; Miyata T; Vanhoorelbeke K

doi:10.1038/nrdp.2017.20

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Journal article

Thrombotic thrombocytopenic purpura.

Kremer Hovinga JA Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Freiburgstrasse, Bern, Switzerland.
Coppo P Centre de Référence des Microangiopathies Thrombotiques, Service d' Hématologie, Hôpitaux Universitaires de l'Est Parisien et Université Pierre et Marie Curie (Paris 6), Paris, France.
Lämmle B Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Freiburgstrasse, Bern, Switzerland.
Moake JL Department of Bioengineering, Rice University, Houston, Texas, USA.
Miyata T Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Japan.
Vanhoorelbeke K Laboratory for Thrombosis Research, Interdisciplinary Research Facility Life Sciences, Katholieke Universiteit Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.

2017-04-07

Published in:

Nature reviews. Disease primers. - 2017

Purpura, Thrombotic Thrombocytopenic

English Thrombotic thrombocytopenic purpura (TTP; also known as Moschcowitz disease) is characterized by the concomitant occurrence of often severe thrombocytopenia, microangiopathic haemolytic anaemia and a variable degree of ischaemic organ damage, particularly affecting the brain, heart and kidneys. Acute TTP was almost universally fatal until the introduction of plasma therapy, which improved survival from <10% to 80-90%. However, patients who survive an acute episode are at high risk of relapse and of long-term morbidity. A timely diagnosis is vital but challenging, as TTP shares symptoms and clinical presentation with numerous conditions, including, for example, haemolytic uraemic syndrome and other thrombotic microangiopathies. The underlying pathophysiology is a severe deficiency of the activity of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), the protease that cleaves von Willebrand factor (vWF) multimeric strings. Ultra-large vWF strings remain uncleaved after endothelial cell secretion and anchorage, bind to platelets and form microthrombi, leading to the clinical manifestations of TTP. Congenital TTP (Upshaw-Schulman syndrome) is the result of homozygous or compound heterozygous mutations in ADAMTS13, whereas acquired TTP is an autoimmune disorder caused by circulating anti-ADAMTS13 autoantibodies, which inhibit the enzyme or increase its clearance. Consequently, immunosuppressive drugs, such as corticosteroids and often rituximab, supplement plasma exchange therapy in patients with acquired TTP.

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