title: New variant of type II von Willebrand's disease with structural abnormality of plasma von Willebrand factor in a patient with very mild bleeding history.
abstract: A new variant of von Willebrand's disease has been discovered in 2 members of a Macedonian family of 6. The proband, an 8-year-old boy, showed a prolonged bleeding episode on 1 occasion. Ristocetin-induced platelet aggregation and bleeding time were normal. In plasma, ristocetin cofactor activity (RCo) and von Willebrand factor (vWf) antigen were reduced to the same clearly low level. The determination of vWf antigen of platelets resulted in borderline values, while RCo was clearly reduced. Low- and intermediate-resolution agarose gel electrophoresis showed absence of the largest multimers in plasma vWf, and slight reduction in platelet vWf. High-resolution gels revealed abnormal multimeric structure only in plasma vWf. The smaller multimers could be resolved in a broad central band flanked by 4 fainter satellite bands; however, satellite bands close to the central band were more intense, and more distant ones were fainter, compared to normal plasma. The central band of the fastest-moving multimer was markedly intensified, and the mobility of the whole quintuplet was slightly reduced. Heredity seems to be autosomal-dominant. No mutation was found in exon 28 of the vWf gene. Because there was only 1 mild bleeding episode in the family, this structural variation seems to have only little clinical consequence. We conclude that this vWf abnormality is different from those observed in other type II variants previously described. Based on the revised classification by the International Society on Thrombosis and Haemostasis, we proposed designation type 2A-Bern for this new subtype.
authors.affiliation: Department of Diagnostics, Swiss Red Cross, Berne.
authors.forename: P
authors.initials: P
authors.lastname: Baillod
authors.forename: C
authors.initials: C
authors.lastname: Gaucher
authors.forename: B
authors.initials: B
authors.lastname: Affolter
authors.forename: C
authors.initials: C
authors.lastname: Mazurier
authors.forename: R
authors.initials: R
authors.lastname: Pflugshaupt
mesh_terms: D001483:Base Sequence; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism; D002648:Child; D017931:DNA Primers; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012310:Ristocetin / Q000494:pharmacology; D014842:von Willebrand Diseases / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D014841:von Willebrand Factor / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D017931:DNA Primers; D014841:von Willebrand Factor; D012310:Ristocetin