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Acquired thrombotic thrombocytopenic purpura

Journal: Hämostaseologie
ISSN: 0720-9355
Topic:

Thrombotic microangiopathies

DOI: http://dx.doi.org/10.5482/HAMO-12-12-0023
Issue: Issues of 2013 (Vol. 33): Issue 2 2013 (77-188)
Pages: 121-130

Acquired thrombotic thrombocytopenic purpura

Development of an autoimmune response

M. Schaller (1), J.-D. Studt (2), J. Voorberg (3), J. A. Kremer Hovinga (1)

(1) Department of Haematology and Central Haematology Laboratory, Haemostasis Research Laboratory, Inselspital, Bern University Hospital and University of Bern, Switzerland; (2) Division of Haematology, University Hospital Zürich, Switzerland; (3) Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands

Summary

The von Willebrand factor (VWF)-cleaving metalloprotease, ADAMTS13 (adisintegrin and metalloprotease with thrombospondin type 1 motifs-13) is the only known target of the dysregulated immune response in acquired TTP. Autoantibodies to ADAMTS13 either neutralize its activity or accelerate its clearance, thereby causing a severe deficiency of ADAMTS13 in plasma. As a consequence, size regulation of VWF is impaired and the persistence of ultra-large VWF (ULVWF) multimers facilitates microvascular platelet aggregation causing microangiopathic haemolytic anaemia and ischaemic organ damage. Autoimmune TTP although a rare disease with an annual incidence of 1.72 cases has a mortality rate of 20% even with adequate therapy. We describe the mechanisms involved in ADAMTS13 autoimmunity with a focus on the role of B- and T-cells in the pathogenesis of this disorder. We discuss the potential translation of recent experimental findings into future therapeutic concepts for the treatment of acquired TTP.

Keywords

autoimmunity, ADAMTS13, TTP, autoantibodies, Thromobotic thrombocytopenic purpura

DOI

http://dx.doi.org/10.5482/HAMO-12-12-0023

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