A novel approach to laboratory assessment and reporting of platelet von Willebrand factor

Abstract

The interaction of platelets with von Willebrand factor is essential for primary hemostasis. Concentration and activity of plasma von Willebrand factor are routine parameters in the assessment of hemostasis disorders. In addition to plasma von Willebrand factor, platelet von Willebrand factor, synthesized in megakaryocytes and stored in α-granules of circulating platelets, is known to contribute to primary hemostasis and the microenvironment of thrombus formation. The laboratory assessment of platelet von Willebrand factor however is cumbersome and not widely established as a routine parameter. We here propose a method for laboratory assessment and reporting of platelet von Willebrand factor potentially useful for laboratory routines in specialized laboratories. Our model allows to describe platelet von Willebrand factor as 1. the concentration of platelet von Willebrand factor in whole blood, 2. the amount of platelet von Willebrand factor in a sample with a defined concentration of 1000 platelets/nl, and 3. the concentration of platelet von Willebrand factor in one platelet. According to our results in healthy individuals, the proportion of platelet von Willebrand factor activity is estimated to be about 10% of total von Willebrand factor in human plasma under physiological circumstances. The concentration of platelet von Willebrand factor is estimated to be 0.4 IU/ml in a sample with a defined concentration of 1000 platelets/nl and to be about 42 IU/ml in one platelet (both expressed as VWF:Ag).

Keywords:

• Laboratory assessment
• primary hemostasis
• platelet
• von Willebrand factor

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Acknowledgements

We are indebted to Michaela Müller, Gabriele Gärtner and Susanne Felsmann for their excellent support in the laboratory.

Disclosure statement

TK received travel support from LFB and Takeda, outside the submitted work. IP has received honoraria or grants from LFB, Novo Nordisk, Roche, Shire, and Sobi for participating in advisory boards, speaker bureaus, and/or research and reports fees from Sobi, LFB, Roche, Shire, grants from Novo Nordisk, outside the submitted work. HWO declares no potential conflicts of interest. MS has received scientific research grants from Shire, Pfizer and lecture and travel fees from Roche, Sobi, LFB, Bayer, Shire, Pfizer, Uniqure, NovoNordisk and CSL Behring, outside the submitted work. PM served on an advisory board for CSL Behring, and has received lecture fees from CSL Behring, NovoNordisk and Sobi, and grants from Shire (Baxalta), Pfizer, Biotest, Roche, outside the submitted work.

Author contributions

IP, TK, HO, MS, PM all contributed to the design of the study, data analysis as well as to drafting, revising and approval of the final manuscript. TK and HO contributed to data acquisition.

Additional information

Funding

Thorsten Kragh and Michael Spannagl received a research grant for the topic primary haemostasis from the German society “Gesellschaft für Thrombose- und Hämostaseforschung”.