Journal article
von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins
Blood, Vol.109(6), pp.2424-2429
Hemostasis, Thrombosis, and Vascular Biology
03/15/2007
DOI: 10.1182/blood-2006-06-028241
PMCID: PMC1852205
PMID: 17119108
Abstract
von Willebrand factor (VWF) protects factor VIII (FVIII) from proteolysis and mediates the initial contact of platelets with the injured vessel wall, thus playing an important role in hemostasis and thrombosis. VWF is crucial for the formation of occlusive thrombi at arterial shear rates. However, with only a few conflicting studies published, the role of VWF in venous thrombosis is still unclear. Using gene-targeted mice, we show that in ferric chloride–injured veins platelet adhesion to subendothelium is decreased and thrombus growth is impaired in
VWF
−/−
mice when compared with wild type (WT). We also observed increased embolization in the
VWF
−/−
mice, which was due to lower FVIII levels in these mice as recombinant factor VIII (r-FVIII) restored thrombus stability. Despite normalization of blood clotting time and thrombus stability after r-FVIII infusion, the
VWF
−/−
venules did not occlude. Transgenic platelets lacking the VWF receptor GPIbα extracellular domain showed decreased adhesion to injured veins. But, after a delay, all the injured venules occluded in these transgenic mice. Thus, VWF likely uses other adhesion receptors besides GPIbα in thrombus growth under venous shear conditions. Our studies document crucial roles for VWF and FVIII in experimental thrombosis under venous flow conditions in vivo.
Details
- Title: Subtitle
- von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins
- Creators
- Anil K. Chauhan - Harvard Medical SchoolJanka Kisucka - Harvard UniversityColin B. Lamb - California Institute for Biomedical ResearchWolfgang Bergmeier - Harvard UniversityDenisa D. Wagner - Harvard University
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.109(6), pp.2424-2429
- Publisher
- American Society of Hematology
- Series
- Hemostasis, Thrombosis, and Vascular Biology
- DOI
- 10.1182/blood-2006-06-028241
- PMID
- 17119108
- PMCID
- PMC1852205
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 03/15/2007
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360051502771
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