title: Congenital microangiopathic hemolytic anemia and thrombocytopenia with unusually large von Willebrand factor multimers and von Willebrand factor-cleaving protease.
abstract: Infantile or congenital cases of thrombotic microangiopathy have been reported that were familial and characterized by ongoing microangiopathic hemolysis and thrombocytopenia in the absence of regular fresh-frozen plasma transfusions. The authors describe a child with congenital microangiopathic hemolytic anemia and thrombocytopenia (CMHAT) who has received regular fresh-frozen plasma transfusions since infancy and has never had thrombotic complications. von Willebrand factor (vWF)-cleaving protease activity was studied in the patient's pretransfusion and posttransfusion plasma samples as well as in her parents' plasma. The effects of the patient's and a control subject's plasma on human microvascular endothelial cells were also investigated. Unusually large vWF multimers were present in the patient's plasma both before transfusion (thrombocytopenic) and after transfusion. Unlike cases of chronic relapsing thrombotic thrombocytopenic purpura, vWF-cleaving protease activity was present and treatment of cultured human endothelial cells with the patient's plasma did not induce apoptosis. These findings suggest that the patient with CMHAT may represent a different group in the broad spectrum of thrombotic microangiopathies.
authors.affiliation: Children's Hospital of Michigan, Division of Hematology/Oncology, Wayne State University, Detroit, Michigan 48201, USA. ssavasan@med.wayne.edu
authors.forename: S
authors.initials: S
authors.lastname: Savaşan
authors.forename: J W
authors.initials: JW
authors.lastname: Taub
authors.forename: S
authors.initials: S
authors.lastname: Buck
authors.forename: M
authors.initials: M
authors.lastname: Botterill
authors.forename: M
authors.initials: M
authors.lastname: Furlan
authors.forename: Y
authors.initials: Y
authors.lastname: Ravindranath
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000745:Anemia, Hemolytic, Congenital / Q000097:blood* / Q000150:complications / Q000201:enzymology; D017209:Apoptosis; D001803:Blood Transfusion; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008666:Metalloendopeptidases / Q000097:blood*; D013921:Thrombocytopenia / Q000097:blood* / Q000150:complications / Q000151:congenital / Q000201:enzymology; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human