Evaluation of Various VWF Concentrates Regarding Their Ability to Mediate Platelet Binding to Collagen

Introduction

Von Willebrand disease is characterized by a quantitative or qualitative deficiency of von Willebrand factor (VWF). In many cases, concentrates containing VWF and factor VIII (FVIII) are used to treat bleeding or to facilitate surgical procedures.

Many studies have already compared the clinical effectiveness of the various available VWF concentrates, even from the perspective of laboratory results, particularly ristocetin cofactor activity (VWF:RCo) or collagen binding activity (VWF:CB). However, relatively few studies have focused on their ability to mediate platelet adhesion to collagen under physiological flow conditions (known as shear stress).

10 VWF-Containing Concentrates Evaluated by Various Tests

This London study evaluated 10 available commercial concentrates with regard to the relationship of VWF and platelet binding. For VWF concentrates, the following were measured: antigen (VWF:Ag), VWF:CB, VWF:RCo, FVIII:C content, ADAMTS13, VWF multimer profile, and glycan content. An MPB binding assay was also used to measure the content of thiol-free VWF groups. An in vitro flow assay was used to measure the ability of the individual concentrates to mediate platelet binding to collagen.

Results

VWF multimer analysis showed a reduced prevalence of high molecular weight multimers in 4 concentrates (Alphante, Octanate, Haemoctin, 8Y). The distribution of high molecular weight multimers in the other 6 concentrates (Optivate, Wilate, Fandhi, Wilfactin, Haemate P, Voncento) was similar to that of control plasma. Platelet capture after 5 minutes of perfusion was similar for all concentrates, with Alphante, Octanate, and Haemoctin showing the lowest rates of platelet binding after 1 minute of perfusion. The content of thiol-free groups or ADAMTS13 levels varied between concentrates but did not affect function.

Conclusion

The tests conducted indicate that Alphanate, Octanate, and Haemoctin do not contain high molecular weight VWF multimers and also showed the lowest platelet binding rates in the platelet binding test for these 3 concentrates. This suggests a likely necessity for the presence of high molecular weight VWF multimers for the initial capture and binding of platelets to collagen.

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Source: Riddell A., Vinayagam S., Gomez K. et al. Evaluation of von Willebrand factor concentrates by platelet adhesion to collagen using an in vitro flow assay. Res Pract Thromb Haemost 2018; 3 (1): 126-135, doi: 10.1002/rth2.12166.