Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis.
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.


OBJECTIVE
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.


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-/-.


CONCLUSIONS
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.
Blood Research Institute, BloodCenter of Wisconsin, Department of Pediatrics, Medical College of Wisconsin, Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI 53226, USA. sachiko.kanaji@bcw.edu
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Kanaji
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Fahs
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Shi
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Haberichter
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Montgomery
D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D003094:Collagen / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004837:Epinephrine / Q000008:administration & dosage; D006487:Hemostasis / Q000187:drug effects; D007279:Injections, Subcutaneous; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010973:Platelet Adhesiveness / Q000187:drug effects; D013997:Time Factors; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
D014841:von Willebrand Factor; D003094:Collagen; D004837:Epinephrine