title: The factor VIII/von Willebrand factor ratio discriminates between reduced synthesis and increased clearance of von Willebrand factor.
abstract: It is often stated that a decrease in Von Willebrand factor (VWF), the carrier protein of factor VIII, results in a concordant change in factor VIII. Clinical data suggest that this is not always the case and we hypothesized that the ratio between factor VIII and VWF depends on the genetic defect that causes the VWF deficiency. We have analyzed the ratio between plasma factor VIII and VWF in several subtypes of Von Willebrand Disease and we show that the ratio is increased when VWF synthesis is reduced, but that the ratio remains one when VWF clearance is increased. These observations could be of clinical importance as an increased factor VIII/VWF ratio in combination with a borderline VWF level may indicate the presence of a true genetic defect, possibly a VWF null allele.
authors.affiliation: Department of Hematology, Hemostasis and Thrombosis Research Center, Leiden University Medical Center, The Netherlands. H.C.J.Eikenboom@LUMC.nl
authors.forename: Jeroen C J
authors.initials: JC
authors.lastname: Eikenboom
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castaman
authors.forename: Pieter W
authors.initials: PW
authors.lastname: Kamphuisen
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Bertina
mesh_terms: D000483:Alleles; D000941:Antigens / Q000032:analysis*; D005169:Factor VIII / Q000032:analysis*; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009154:Mutation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D014842:von Willebrand Diseases / Q000097:blood* / Q000145:classification / Q000235:genetics; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D000941:Antigens; D019038:Platelet Glycoprotein GPIb-IX Complex; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D005169:Factor VIII