von Willebrand Factor-Cleaving Protease (ADAMTS13) in the Course of Stem Cell Transplantation

Karim Kentouche; Felix Zintl; Dorothea Angerhaus; Dietlinde Fuchs; Johann Hermann; Reinhard Schneppenheim; Ulrich Budde

doi:10.1055/s-2006-939765

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2006; 32(2): 098-104
DOI: 10.1055/s-2006-939765

von Willebrand Factor-Cleaving Protease (ADAMTS13) in the Course of Stem Cell Transplantation

Karim Kentouche¹ , Felix Zintl¹ , Dorothea Angerhaus² , Dietlinde Fuchs¹ , Johann Hermann¹ , Reinhard Schneppenheim³ , Ulrich Budde²

¹Department of Hematology, Children's Hospital, Friedrich Schiller University, Jena, Germany
²Laboratory Association Prof. Arndt and Partners, Coagulation Laboratory, Hamburg, Germany
³Children's University Hospital Hamburg-Eppendorf, Germany

Abstract

ABSTRACT

Transplantation-associated microangiopathy (TAM) is a severe complication of stem cell transplantation. Although TAM shares many features with idiopathic thrombotic thrombocytopenic purpura or hemolytic uremic syndrome, the prognosis of TAM is worse. Clinical similarities and the observation that uncleaved ultralarge von Willebrand factor (ULVWF) multimers are found in the circulation of patients suffering from TAM suggest a defect in VWF proteolysis that may be due to a deficiency in ADAMTS13 activity. In this study the course of 28 consecutive patients, who received an allogeneic stem cell transplant was correlated to ADAMTS13 activity. Before stem cell transplantation, mean ADAMTS13 activity was within normal range. Within the first 8 weeks, mean activity declined to less than half the baseline activity. Furthermore, most of the patients showed normalization of ADAMTS13 activity. Low levels of ADAMTS13 activity were not correlated with clinical signs of thrombotic microangiopathy. However, two patients with clinical TAM had the lowest activity of all patients when suffering a severe bout of microangiopathy. Plasma exchange was not able to normalize ADAMTS13 deficiency in these patients, suggesting inactivation or consumption of ADAMTS13 activity in TAM.

KEYWORDS

Stem cell transplantation - thrombotic thrombocytopenic purpura - hemolytic uremic syndrome - transplantation-associated microangiopathy - von Willebrand factor - ADAMTS13 - plasma exchange

Full Text

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Karim KentoucheM.D.

Department of Hematology, Children's Hospital, Friedrich-Schiller-University Jena

Kochstr. 2, 07745 Jena, Germany

Email: Karim.Kentouche@med.uni-jena.de