von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP.
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von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP. / Schneppenheim, Reinhard; Ulrich, Budde; Oyen, Florian; Angerhaus, Dorothea; Aumann, Volker; Drewke, Elke; Hassenpflug, Wolf; Häberle, Johannes; Kentouche, Karim; Kohne, Elisabeth; Kurnik, Karin; Müller-Wiefel, Dirk E.; Obser, Tobias; Santer, René; Sykora, Karl-Walter.
In: BLOOD, Vol. 101, No. 5, 5, 2003, p. 1845-1850.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP.
AU - Schneppenheim, Reinhard
AU - Ulrich, Budde
AU - Oyen, Florian
AU - Angerhaus, Dorothea
AU - Aumann, Volker
AU - Drewke, Elke
AU - Hassenpflug, Wolf
AU - Häberle, Johannes
AU - Kentouche, Karim
AU - Kohne, Elisabeth
AU - Kurnik, Karin
AU - Müller-Wiefel, Dirk E.
AU - Obser, Tobias
AU - Santer, René
AU - Sykora, Karl-Walter
PY - 2003
Y1 - 2003
N2 - Thrombotic thrombocytopenic purpura (TTP) is caused by the persistence of the highly reactive high-molecular-weight multimers of von Willebrand factor (VWF) due to deficiency of the specific VWF-cleaving protease (VWF-CP) ADAMTS13, resulting in microangiopathic disease. The acquired form is caused by autoantibodies against VWF-CP, whereas homozygous or compound heterozygous mutations of ADAMTS13 are responsible for recessively inherited TTP. We investigated 83 children with hemolytic or thrombocytopenic episodes with or without additional neurologic symptoms or renal failure. The presumed diagnosis was chronic idiopathic thrombocytopenic purpura (ITP; n = 50), TTP (n = 8), hemolytic uremic syndrome (HUS; n = 24), and Evans syndrome (n = 1). A severe deficiency of VWF-CP (<or = 5%) was found in all investigated patients with TTP and in none of those with HUS. Additionally, 2 of 50 patients with a prior diagnosis of ITP were deficient for VWF-CP. Antibodies against VWF-CP were found in 4 children. Mutation analysis of the ADAMTS13 gene in the patients deficient in VWF-CP by direct sequencing of all 29 exons identified 8 different mutations, suggesting the hereditary form of TTP in 1 patient with ITP, in the patient with Evans syndrome, and in 5 of the 8 patients with TTP. The phenotype of TTP in childhood can be rather variable. Besides the classical clinical picture, oligosymptomatic forms may occur that can delay the identification of patients at risk.
AB - Thrombotic thrombocytopenic purpura (TTP) is caused by the persistence of the highly reactive high-molecular-weight multimers of von Willebrand factor (VWF) due to deficiency of the specific VWF-cleaving protease (VWF-CP) ADAMTS13, resulting in microangiopathic disease. The acquired form is caused by autoantibodies against VWF-CP, whereas homozygous or compound heterozygous mutations of ADAMTS13 are responsible for recessively inherited TTP. We investigated 83 children with hemolytic or thrombocytopenic episodes with or without additional neurologic symptoms or renal failure. The presumed diagnosis was chronic idiopathic thrombocytopenic purpura (ITP; n = 50), TTP (n = 8), hemolytic uremic syndrome (HUS; n = 24), and Evans syndrome (n = 1). A severe deficiency of VWF-CP (<or = 5%) was found in all investigated patients with TTP and in none of those with HUS. Additionally, 2 of 50 patients with a prior diagnosis of ITP were deficient for VWF-CP. Antibodies against VWF-CP were found in 4 children. Mutation analysis of the ADAMTS13 gene in the patients deficient in VWF-CP by direct sequencing of all 29 exons identified 8 different mutations, suggesting the hereditary form of TTP in 1 patient with ITP, in the patient with Evans syndrome, and in 5 of the 8 patients with TTP. The phenotype of TTP in childhood can be rather variable. Besides the classical clinical picture, oligosymptomatic forms may occur that can delay the identification of patients at risk.
M3 - SCORING: Zeitschriftenaufsatz
VL - 101
SP - 1845
EP - 1850
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 5
M1 - 5
ER -