title: Diurnal variation of von Willebrand factor in plasma: the Bispebjerg study of diurnal variations.
abstract: BACKGROUND
  Quantitation of von Willebrand factor (VWF) in plasma is a central element in assessing von Willebrand disease (VWD). VWF activity is known to vary, which has partly been ascribed to biological and preanalytical variation. However, a possible diurnal expression of VWF has not been thoroughly tested.
  
  
  OBJECTIVE
  We examined whether VWF antigen and VWF activity in plasma display a diurnal profile in healthy young males, and whether such variation is related to changes in release or elimination.
  
  
  METHODS
  Plasma from 20 healthy young males was collected at 9 time-points over 24 h (15 h of light and 9 h of darkness); the plasma concentration of melatonin was used as an internal control to confirm the normal 24-h rhythms of the individual participants.
  
  
  RESULTS
  The data, analyzed by rhythmometric statistics, revealed a significant variation (P = 0.02) and total amplitude of 22.6% in VWF antigen concentrations over the 24-h period. A pronounced variation in VWF activity was also observed, although not significant according to the 24-h statistical model. To examine whether the diurnal pattern was related to changes in elimination or secretion, the ratio between (i) coagulation factor VIII and VWF and (ii) VWF propeptide and VWF was determined. Taken together, the data suggest changes in release and not in clearance.
  
  
  CONCLUSIONS
  Diurnal variation in von Willebrand antigen and activity in plasma represents an important aspect of the biological variation. Standardized time-of-day plasma sampling for quantitation of VWF in VWD patients seems warranted.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Annette
authors.initials: A
authors.lastname: Timm
authors.forename: Jan
authors.initials: J
authors.lastname: Fahrenkrug
authors.forename: Henrik L
authors.initials: HL
authors.lastname: Jørgensen
authors.forename: Henriette P
authors.initials: HP
authors.lastname: Sennels
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
mesh_terms: D002940:Circadian Rhythm; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D012016:Reference Values; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor
keywords: diurnal rhythm; von Willebrand disease; von Willebrand factor