Diurnal variation of von Willebrand factor in plasma: the Bispebjerg study of diurnal variations.

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.

Plasma ADAMTS-13 protein is not associated with portal hypertension or hemodynamic changes in patients with cirrhosis.

BACKGROUND: Activated hepatic stellate cells synthesize the matrix metalloprotease ADAMTS13, which may be involved in the development of liver cirrhosis and portal hypertension. Plasma ADAMTS13 activity has been reported as both increased and decreased in cirrhosis, but ADAMTS13 protein has not previously been examined. AIM: To evaluate ADAMTS13 protein in the hepatic circulation and the relation to disease severity, portal pressure, and systemic hemodynamics in cirrhotic patients. METHODS: Sixty-one cirrhotic patients (Child class: A=22; B=21; C=18) and nine healthy controls underwent a liver vein catheterization with measurement of splanchnic and systemic hemodynamics, and plasma ADAMTS13 protein concentration in a hepatic vein and the femoral artery. RESULTS: ADAMTS13 protein concentrations were increased in cirrhotic patients compared with controls (774ng/ml [IQR: 585-955] vs. 538ng/ml [IQR: 484-631], p<0.03). There were no significant correlations to MELD score, Child Pugh score, portal pressure, nor systemic vascular resistance or cardiac output. CONCLUSIONS: The increased concentration of ADAMTS13 protein in the hepatic circulation may reflect an increased number of active hepatic stellate cells in cirrhosis. However, ADAMTS13 was unrelated to portal hypertension and systemic hemodynamics. In conclusion, ADAMTS13 does not appear to be associated to disease severity or the hemodynamic derangement in patients with cirrhosis.

Comparison of automated von Willebrand factor activity assays.

INTRODUCTION: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Measurement of von Willebrand factor (VWF) activity in plasma is often based on platelet agglutination stimulated by the ristocetin cofactor activity. Novel assays, based on latex beads with recombinant glycoprotein Ib instead of platelets, have recently been developed but it is unclear whether these can improve the diagnostic capability for VWD. AIM: To compare four automated VWF activity methods in a mixed population of patients referred for evaluation of bleeding tendency. METHODS: The analytical performances of three ristocetin and one non-ristocetin cofactor activity assays were compared in 170 consecutive plasma samples from patients referred for VWD evaluation. RESULTS: All methods correlated well with concordance correlation coefficients ranging from 0.90-0.95. However, when comparing the VWF activity/antigen ratios in samples classified as having VWD (activity <0.4 IU/mL) the number of samples below a ratio of 0.7 differed between 16 and 8%. CONCLUSION: Despite overall correlation between assays we found that differences in classification power might interfere with the interpretation of individual samples.

Atrial natriuretic peptides in plasma.

Measurement of cardiac natriuretic peptides in plasma has gained a diagnostic role in the assessment of heart failure. Plasma measurement is though hampered by the marked instability of the hormones, which has led to the development of analyses that target N-terminal fragments from the prohormone. These fragments are stable in plasma and represent surrogate markers of the actual natriuretic hormone. Post-translational processing of the precursors, however, is revealing itself to be a complex event with new information still being reported on proteolysis, covalent modifications, and amino acid derivatizations. In this mini-review, we summarize measurement of the principal cardiac hormone, e.g. atrial natriuretic peptide (ANP) and its precursor fragments. We also highlight some of the analytical pitfalls and problems and the concurrent clinical "proof of concept". We conclude that biochemical research into proANP-derived peptides is still worthy of attention and that new biological insight may change our chemical perception of the markers.