Faculty Collaboration Database

Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis. J Thromb Haemost 2012 Aug;10(8):1646-52

Date

05/31/2012

Pubmed ID

22642380

Pubmed Central ID

PMC3419786

DOI

10.1111/j.1538-7836.2012.04797.x

Scopus ID

2-s2.0-84865237107 (requires institutional sign-in at Scopus site)   108 Citations

Abstract

BACKGROUND: von Willebrand factor (VWF) is a glycoprotein that plays an important role in primary hemostasis. VWF is synthesized and stored in endothelial cells (ECs) and megakaryocytes/platelets. Plasma VWF is primarily derived from ECs and is generally believed to be essential for hemostasis. VWF synthesized in megakaryocytes is stored in platelet α-granules, from which it is released following platelet activation. The relative contribution of VWF stored in ECs or megakaryocytes/platelets or present in plasma to hemostasis is not clear.

OBJECTIVES: We investigated whether EC-derived VWF plays the major role in hemostasis while the contribution of platelet-derived VWF is negligible, or if platelet-derived VWF also significantly contributes to hemostasis.

METHODS AND RESULTS: Mice expressing VWF only in ECs (EC-VWF) or platelets (Plt-VWF) were created by reciprocal bone marrow transplantation between C57BL/6J (WT) and VWF knockout mice (VWF-/-). Plasma VWF levels in EC-VWF were similar to WT. Plt-VWF mice had a trace amount of VWF in their plasma while VWF levels in platelet lysate were comparable to WT. Tail bleeding time was normal in EC-VWF. Interestingly, Plt-VWF showed partially corrected bleeding time and significantly decreased blood loss volume compared with VWF-/-. Adhesion of platelets perfused over immobilized collagen under shear stress was significantly higher in both EC-VWF and Plt-VWF compared with VWF-/-.

CONCLUSION: VWF synthesized in ECs is sufficient to support hemostasis in VWF-/- mice, and VWF produced in megakaryocytes/platelets can also contribute to hemostasis in the absence of EC-derived VWF.

Author List

Kanaji S, Fahs SA, Shi Q, Haberichter SL, Montgomery RR

Authors

Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Qizhen Shi MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bleeding Time
Blood Platelets
Bone Marrow Transplantation
Collagen
Endothelial Cells
Epinephrine
Hemostasis
Injections, Subcutaneous
Megakaryocytes
Mice
Mice, Inbred C57BL
Mice, Knockout
Platelet Adhesiveness
Time Factors
von Willebrand Factor