TY - JOUR

T1 - Diurnal variation of von Willebrand factor in plasma

T2 - the Bispebjerg study of diurnal variations

AU - Timm, Annette

AU - Fahrenkrug, Jan

AU - Jørgensen, Henrik L

AU - Sennels, Henriette P

AU - Goetze, Jens P

N1 - © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2014/7

Y1 - 2014/7

N2 - 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.OBJECTIVES: 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.

AB - 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.OBJECTIVES: 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.

KW - Circadian Rhythm

KW - Enzyme-Linked Immunosorbent Assay

KW - Humans

KW - Male

KW - Reference Values

KW - von Willebrand Factor

U2 - 10.1111/ejh.12298

DO - 10.1111/ejh.12298

M3 - Journal article

C2 - 24571735

VL - 93

SP - 48

EP - 53

JO - European Journal of Haematology

JF - European Journal of Haematology

SN - 0902-4441

IS - 1

ER -