Comparison of von Willebrand factor (VWF) activity levels determined by HemosIL AcuStar assay and HemosIL LIA assay with ristocetin cofactor assay by aggregometry

Haemophilia ◽  
2016 ◽  
Vol 22 (3) ◽  
pp. e200-e207 ◽  
Author(s):  
S. Sagheer ◽  
S. Rodgers ◽  
O. Yacoub ◽  
R. Dauer ◽  
S. Mcrae ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Activity Levels ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor

Plasma Derived von Willebrand Factor Preparations: Collagen Binding and Ristocetin Cofactor Activities

1997 ◽  
Vol 78 (02) ◽  
pp. 930-933 ◽  
Author(s):  
Ping Chang ◽  
D L Aronson
Keyword(s):  
Von Willebrand Factor ◽  
Functional Activity ◽  
Binding Activity ◽  
Collagen Binding ◽  
Binding Function ◽  
Cofactor Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

SummaryFive plasma preparations (11 lots) used in the treatment of von Willebrand’s disease (vWD) were evaluated. The collagen binding function of von Willebrand factor (vWF) containing preparations was compared with the ristocetin cofactor activity and the vWF antigen. Some preparations have higher ratio of functional activity (ristocetin cofactor and collagen binding) relative to the antigen than is found in normal plasma. The ristocetin cofactor activity and the collagen binding activity are tightly correlated (r = .95). Ultracentrifugal (UCF) analysis was used to compare the size distribution of vWf antigen, ristocetin cofactor and collagen binding activity. The sedimentation of all of the vWF parameters in the plasma products was slower than in plasma. In plasma products the ristocetin cofactor activity sediments the most rapidly, the collagen binding activity is slower and the antigen the slowest. The collagen/antigen ratio decreases with decreasing vWF size. Assignment of potency to vWF containing preparations utilizing the collagen binding activity may be more precise and as accurate as with the traditional ristocetin cofactor assay.

Population Pharmacokinetic Modeling of von Willebrand Factor Activity in von Willebrand Disease Patients after Desmopressin Administration

2020 ◽  
Vol 120 (10) ◽  
pp. 1407-1416
Author(s):  
Nico C. B. de Jager ◽  
Jessica M. Heijdra ◽  
Quincy Kieboom ◽  
Marieke J. H. A. Kruip ◽  
Frank W. G. Leebeek ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Time Profile ◽  
Von Willebrand Disease ◽  
Activity Level ◽  
Population Pharmacokinetic ◽  
Activity Levels ◽  
Interpatient Variability ◽  
Starting Point ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Objective Most von Willebrand disease (VWD) patients can be treated with desmopressin during bleeding or surgery. Large interpatient variability is observed in von Willebrand factor (VWF) activity levels after desmopressin administration. The aim of this study was to develop a pharmacokinetic (PK) model to describe, quantify, and explain this variability. Methods Patients with either VWD or low VWF, receiving an intravenous desmopressin test dose of 0.3 µg kg−1, were included. A PK model was derived on the basis of the individual time profiles of VWF activity. Since no VWF was administered, the VWF dose was arbitrarily set to unity. Interpatient variability in bioavailability (F), volume of distribution (V), and clearance (Cl) was estimated. Results The PK model was developed using 951 VWF activity level measurements from 207 patients diagnosed with a VWD type. Median age was 28 years (range: 5–76), median predose VWF activity was 0.37 IU/mL (range: 0.06–1.13), and median VWF activity response at peak level was 0.64 IU/mL (range: 0.04–4.04). The observed PK profiles were best described using a one-compartment model with allometric scaling. While F increased with age, Cl was dependent on VWD type and sex. Inclusion resulted in a drop in interpatient variability in F and Cl of 81.7 to 60.5% and 92.8 to 76.5%, respectively. Conclusion A PK model was developed, describing VWF activity versus time profile after desmopressin administration in patients with VWD or low VWF. Interpatient variability in response was quantified and partially explained. This model is a starting point toward more accurate prediction of desmopressin dosing effects in VWD.

scholarly journals Selective absence of large forms of factor VIII/von Willebrand factor in acquired von Willebrand's syndrome. Response to transfusion

Blood ◽  
1979 ◽  
Vol 54 (3) ◽  
pp. 600-606 ◽  
Author(s):  
D Meyer ◽  
D Frommel ◽  
MJ Larrieu ◽  
TS Zimmerman
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Procoagulant Activity ◽  
Factor Viii Related Antigen ◽  
Cofactor Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

Abstract A previously healthy elderly man with mucocutaneous bleeding was found to have a benign monoclonal IgG gammapathy associated with criteria for severe von Willebrand disease (Factor VIII procoagulant activity, Factor-VIII-related antigen, and ristocetin cofactor activity, less than 10% of normal). Associated qualitative abnormalities of factor VIII/von Willebrand factor were demonstrated by radiocrossed immunoelectrophoresis and immunoradiometric assay. The late clinical onset and negative family history are in favor of an acquired form of vWD. The monoclonal gammapathy and abnormalities of factor VIII/von Willebrand factor have been stable over a 10-yr period. No inhibitor to Factor VIII procoagulant activity, ristocetin cofactor activity, or Factor-VIII-related antigen could be demonstrated. Following transfusion of cryoprecipitate (with a normal cross immunoelectrophoretic pattern), there was a rapid removal of the large forms of Factor.-VIII-related antigen, paralleled by a decay of ristocetin cofactor activity. The transfusion study of this patient with acquired von Willebrand disease type II (variant of von Willebrand disease) serves to emphasize the relationship between polydispersity of Factor VIII/von Willebrand Factor and functional heterogeneity.

scholarly journals DDAVP in type IIa von Willebrand's disease

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 465-468 ◽  
Author(s):  
HR Gralnick ◽  
SB Williams ◽  
LP McKeown ◽  
ME Rick ◽  
P Maisonneuve ◽  
...  
Keyword(s):  
Factor Viii ◽  
Protease Inhibitors ◽  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Time Period ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor

Abstract 1-D-Amino(8-D-arginine)-vasopressin (DDAVP) infusion in three patients with type IIa von Willebrand's disease (vWD) resulted in a normalization of the factor VIII coagulant, factor VIII-related antigen, and von Willebrand factor (vWF) (ristocetin cofactor) activities and the bleeding time. The normalization of these hemostatic parameters persisted for four hours. Over the same time period there was a marked increase in the quantity of the vWF multimers when blood was collected in the presence of protease inhibitors. The vWF multimers present were even larger than the normal. When blood was collected in the absence of protease inhibitors, a smaller increase in the plasma vWF multimers was observed and fewer of the intermediate and larger vWF multimers were seen; multimers larger than those present in normal plasma were not visualized. The platelet vWF multimers and activities did not change with or without inhibitors. These studies suggest that there is a subgroup of patients with type IIa vWD who respond to DDAVP with complete normalization of their hemostatic abnormalities and whose vWF is sensitive to proteolysis.

CARBOHYDRATE PREVENTS LOSS OF LARGE VON WILLEBRAND FACTOR MULTIMERS BY PROTECTING AGAINST AMINO TERMINAL PROTEOLYTIC CLEAVAGE

1987 ◽  
Author(s):  
A B Federici ◽  
S D Berkowitz
Keyword(s):  
Von Willebrand Factor ◽  
Proteinase Inhibitors ◽  
Enzymatic Digestion ◽  
Terminal Region ◽  
Cleavage Sites ◽  
Amino Terminal ◽  
Carboxy Terminal ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor

We have previously shown that carbohydrate (CHO) protects von Willebrand factor (vWF) from proteolytic degradation. We have now shown that removal of CHO from the vWF subunit exposes additional cleavage sites in the amino terminal region and that cleavages in this region are associated with loss of large multimers. We examined and compared the extent of large multimer loss with sites of subunit cleavage of native and GHO-modified vWF after treatment with plasmin, chymotrypsin, and trypsin. Highly purified vWF was treated with neuraminidase and β-galactosidase in the presence of proteinase inhibitors to remove 90-95% of the sialic acid and 45-50% of the D-galactose without loss of large multimers or diminution of the ristocetin cofactor activity. The extent and approximate location of subunit cleavage was determined by immunoblotting and monoclonal antibody epitope mapping. Multimeric analysis revealed an increasingly greater loss of large multimers when native vWF was digested with plasmin, chymotrypsin, and trypsin, respectively. Large multimer loss was more extensive with each enzyme after CHO-modification of vWF. On subunit analysis, plasmin, chymotrypsin, and trypsin were shown to produce both amino and carboxy terminal fragments. The number, location, and relative quantities of carboxy terminal fragments produced by these enzymes were unchanged after CHO modification. However, digestion of the amino terminal region was considerably more extensive as judged by a marked decrease or absence of the larger fragments seen when native vWF was digested, and by the appearance of new smaller molecular weight species. Thus, enzymatic digestion of vWF after removal of carbohydrate produced new cleavages in the amino terminal region but did not alter the location or extent of carboxy terminal cleavages. Therefore, the greater loss of large multimers that occurs after CHO modification is likely to be the result of cleavages in the amino terminal region of the molecule. It appears that by protecting the vWF subunit against amino terminal cleavage, carbohydrate inhibits the loss of large multimers.

scholarly journals Leukocyte proteases cleave von Willebrand factor at or near the ADAMTS13 cleavage site

Blood ◽  
2009 ◽  
Vol 114 (8) ◽  
pp. 1666-1674 ◽  
Author(s):  
Thomas J. Raife ◽  
Wenjing Cao ◽  
Bonnie S. Atkinson ◽  
Bruce Bedell ◽  
Robert R. Montgomery ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Hot Spot ◽  
Peptide Bond ◽  
Cathepsin G ◽  
Human Neutrophils ◽  
Activity Levels ◽  
Activated Neutrophils ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract The function of von Willebrand factor (VWF) is regulated by proteolysis, which limits its multimeric size and ability to tether platelets. The importance of ADAMTS13 metalloprotease in VWF regulation is demonstrated by the association between severe deficiency of ADAMTS13 and thrombotic thrombocytopenic purpura (TTP). However, ADAMTS13 activity levels do not always correlate with the clinical course of TTP, suggesting that other proteases could be important in regulating VWF. We identified 4 leukocyte proteases that cleave the synthetic VWF substrate FRETS-VWF73 and multimeric VWF. Elastase and proteinase 3 (PR3) cleave multimeric VWF and FRETS-VWF73 at the V1607-T1608 peptide bond; cathepsin G and matrix metalloprotease 9 cleave VWF substrates at the Y1605-M1606 and M1606-V1607 bonds, respectively. Isolated intact human neutrophils cleave FRETS-VWF73 at the V1607-T1608 peptide bond, suggesting that elastase or PR3 expressed on leukocyte surfaces might cleave VWF. In the presence of normal or ADAMTS13-deficient plasma, cleavage of FRETS-VWF73 by resting neutrophils is abolished. However, activated neutrophils retain proteolytic activity toward FRETS-VWF73 in the presence of plasma. Although the in vivo relevance remains to be established, these studies suggest the existence of a “hot spot” of VWF proteolysis in the VWF A2 domain, and support the possibility that activated leukocytes may participate in the proteolytic regulation of VWF.

A two-centre comparative evaluation of new automated assays for von Willebrand factor ristocetin cofactor activity and antigen

Haemophilia ◽  
2013 ◽  
Vol 20 (1) ◽  
pp. 147-153 ◽  
Author(s):  
F. Stufano ◽  
A. S. Lawrie ◽  
S. La Marca ◽  
C. Berbenni ◽  
L. Baronciani ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Comparative Evaluation ◽  
Cofactor Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

von Willebrand Factor Ristocetin Cofactor Activity Correlates with Platelet Function in a High Shear Stress System

2000 ◽  
Vol 84 (10) ◽  
pp. 727-728 ◽  
Author(s):  
Agnès Veyradier ◽  
Edith Fressinaud ◽  
Catherine Boyer-Neumann ◽  
Marc Trossaert ◽  
Dominique Meyer
Keyword(s):  
Shear Stress ◽  
Von Willebrand Factor ◽  
Stress System ◽  
High Shear ◽  
High Shear Stress ◽  
Cofactor Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

scholarly journals Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 58-61 ◽  
Author(s):  
HR Gralnick ◽  
ME Rick ◽  
LP McKeown ◽  
SB Williams ◽  
RI Parker ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Time Factors ◽  
Type I ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Ristocetin Cofactor

Abstract We studied 17 patients with moderate to mild type I von Willebrand's disease (vWd) and correlated the bleeding time with the plasma von Willebrand factor antigen (vWf Ag), the plasma vWf activity (ristocetin cofactor), the platelet vWf Ag, and the platelet vWf activity. We found an excellent correlation between the bleeding time and the platelet vWf activity and, to a lesser extent, between the bleeding time and the platelet vWf Ag. The length of the bleeding time was inversely proportional to the level of the platelet vWf (P less than .001) or, to a lesser extent, the platelet vWf Ag (P less than .05). The plasma vWf Ag and activity did not correlate significantly with the bleeding time. These studies indicate that the platelet vWf is one of the important bleeding time factors in type I vWd and that the platelet vWf plays an important role in the early steps of hemostasis.

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