von Willebrand factor-cleaving protease (ADAMTS13) in the course of stem cell transplantation

TY - JOUR

T1 - von Willebrand factor-cleaving protease (ADAMTS13) in the course of stem cell transplantation

AU - Kentouche, Karim

AU - Zintl, Felix

AU - Angerhaus, Dorothea

AU - Fuchs, Dietlinde

AU - Hermann, Johann

AU - Schneppenheim, Reinhard

AU - Budde, Ulrich

PY - 2006/3/1

Y1 - 2006/3/1

N2 - 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.

AB - 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.

KW - ADAM Proteins

KW - Adolescent

KW - Child

KW - Child, Preschool

KW - Female

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Male

KW - Purpura, Thrombotic Thrombocytopenic

KW - Vascular Diseases

KW - von Willebrand Factor

U2 - 10.1055/s-2006-939765

DO - 10.1055/s-2006-939765

M3 - SCORING: Journal article

C2 - 16575684

VL - 32

SP - 98

EP - 104

JO - SEMIN THROMB HEMOST

JF - SEMIN THROMB HEMOST

SN - 0094-6176

IS - 2

ER -