VWF propeptide and ratios between VWF, VWF propeptide, and FVIII in the characterization of type 1 von Willebrand disease.
During posttranslational modifications of von Willebrand factor (VWF), the VWF propeptide (VWFpp) is cleaved. The ratio between VWFpp and VWF antigen (VWF:Ag) and the ratio between factor VIII (FVIII:C) and VWF:Ag may be used to assess synthesis and clearance of VWF. We analyzed the contribution of VWFpp and ratios of VWFpp/VWF:Ag and FVIII:C/VWF:Ag in the pathophysiological characterization of type 1 von Willebrand disease (VWD) in the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 VWD (MCMDM-1VWD) study. The VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were increased among patients compared with unaffected family members and healthy controls. The VWFpp/VWF:Ag ratio was higher in individuals heterozygous for missense mutations than in those heterozygous for null alleles. In contrast, the FVIII:C/VWF:Ag ratio was highest among heterozygotes for VWF null alleles. The ratios of VWFpp/VWF:Ag and FVIII:C/VWF:Ag indicate that the pathophysiological mechanisms of type 1 VWD include reduced production and accelerated clearance of VWF, but that often a combination of both mechanisms is implicated.
Einthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands. h.c.j.eikenboom@LUMC.nl
Jeroen
J
Eikenboom
Augusto B
AB
Federici
Richard J
RJ
Dirven
Giancarlo
G
Castaman
Francesco
F
Rodeghiero
Ulrich
U
Budde
Reinhard
R
Schneppenheim
Javier
J
Batlle
Maria Teresa
MT
Canciani
Jenny
J
Goudemand
Ian
I
Peake
Anne
A
Goodeve
D016022:Case-Control Studies; D015331:Cohort Studies; D005169:Factor VIII / Q000032:analysis* / Q000235:genetics; D005190:Family; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006801:Humans; D009154:Mutation / Q000502:physiology; D055503:Protein Multimerization; D011498:Protein Precursors / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D056725:von Willebrand Disease, Type 1 / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D014841:von Willebrand Factor / Q000032:analysis* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D011498:Protein Precursors; D014841:von Willebrand Factor; D005169:Factor VIII