Von Willebrand Factor critical for DVT formation
MedWire News: Von Willebrand Factor (VWF)-mediated platelet adhesion is essential for flow reduction-induced deep vein thrombosis (DVT) in mouse models, study findings indicate.
Denisa Wagner (Harvard Medical School, Boston, Massachusetts, USA) and colleagues demonstrated that mice lacking the VWF gene (VWF-/-) are protected from thrombosis induced by complete (stasis) or partial (stenosis) blood flow restriction in the inferior vena cava (IVC).
"Although various risk factors predisposing to DVT have been clinically identified, mechanisms of thrombus initiation remain unclear," note the researchers.
They investigated the role of VWF in DVT because it is already known to play a key role in arterial thrombosis.
In a stenosis model of thrombosis, all (6 of 6) wild-type (WT) mice developed a thrombus within 48 hours after flow restriction in the IVC. In contrast, VWF-/- mice were completely protected from DVT as none of the 14 animals included in the study had a visible thrombus after the same time period.
Moreover, only half (5 of 10) of the mice heterozygous for VWF (VWF+/-) - with 50% of the normal VWF level - developed a thrombus.
In the stasis model of thrombosis, 82% of WT mice developed thrombi, compared with 70% of VWF+/- mice, and only 33% of VWF-/- mice.
The researchers found that repeated infusions of recombinant Factor VIII at a dose that restores normal blood clotting time and thrombus stability in VWF-/- mice did not result in thrombus formation in these animals. This indicates that "impaired coagulation was not the primary reason for the absence of DVT in VWF-/- mice," they say.
Furthermore, intravital microscopy showed that platelet and leukocyte recruitment in the early stages of DVT was considerably higher in IVC from WT versus VWF-/- mice.
Writing in the journal Blood, Wagner and co-authors conclude that their findings "might represent a potential basis for a new approach to pharmacological prophylaxis of venous thrombosis in patients at high risk for DVT."
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By Laura Dean