von Willebrand factor-cleaving protease (ADAMTS13) in the course of stem cell transplantation.
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.
Kentouche
Karim
K
Department of Hematology, Children's Hospital, Friedrich Schiller University, Jena, Germany. Karim.Kentouche@med.uni-jena.de
Zintl
Felix
F
Angerhaus
Dorothea
D
Fuchs
Dietlinde
D
Hermann
Johann
J
Schneppenheim
Reinhard
R
Budde
Ulrich
U
D051722:ADAM Proteins / Q000172:deficiency* / Q000235:genetics; D000071120:ADAMTS13 Protein; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D011697:Purpura, Thrombotic Thrombocytopenic / Q000201:enzymology / Q000209:etiology; D014652:Vascular Diseases / Q000201:enzymology / Q000209:etiology; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human