title: Thrombotic thrombocytopenic purpura.
abstract: 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.
authors.affiliation: Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Freiburgstrasse, Bern, Switzerland.|Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.affiliation: 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
authors.affiliation: Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Freiburgstrasse, Bern, Switzerland.|Center for Thrombosis and Hemostasis, University Medical Center, Mainz, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lämmle
authors.affiliation: Department of Bioengineering, Rice University, Houston, Texas, USA.
authors.forename: Joel L
authors.initials: JL
authors.lastname: Moake
authors.affiliation: Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Japan.|Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.|Department of Biomedical Engineering, Osaka Institute of Technology, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.affiliation: Laboratory for Thrombosis Research, Interdisciplinary Research Facility Life Sciences, Katholieke Universiteit Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Vanhoorelbeke
mesh_terms: D000071120:ADAMTS13 Protein / Q000032:analysis / Q000097:blood; D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D015658:HIV Infections / Q000209:etiology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D056747:Immunomodulation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology; D011697:Purpura, Thrombotic Thrombocytopenic / Q000150:complications* / Q000175:diagnosis* / Q000503:physiopathology; D000069283:Rituximab / Q000494:pharmacology / Q000627:therapeutic use; D022603:Shiga Toxins / Q000009:adverse effects; D013156:Splenectomy / Q000379:methods
chemical_list: D000998:Antiviral Agents; D005938:Glucocorticoids; D007155:Immunologic Factors; D022603:Shiga Toxins; D000069283:Rituximab; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human; D000111:Acetylcysteine