vWD is due to an abnormality ,either quantitative ,absence or qualitative of the vWf.
vWf is a large multimeric glycoprotein that function as :
1.the factor Vlll carrier protein (vWf protect factor Vlll from degradation).
2. required for normal platelet adhesion (vWf binds on platelet to its specific receptor glycoprotein lb & acts as adhesive bridge between the platelet & damaged sub-endothelium at the site of vascular injury
vWf is composed of dimeric subunits that are linked by disulfide bonds to form complex multimers of low ,intermediate & high molecular weights .
The small multimers function mainly as carriers for factor Vlll.
High molecular weight multimers have higher numbers of platelet-binding sites & greater adhesive properties .
Each multimeric subunit has binding sites for the receptor glycoprotein lb on non-activated platelets & the receptor glycoprotein llb/llla on activated platelets,
this facilitates both platelet adhesion & aggregation
Acquired forms of vWD
1. Wilm’s tumor.
2. Congenital hear disease.
3. Systemic lupus erythmatosus.
5. Seizures disorders treated with valproate.
Aortic-valve Stenosis can be complicated by bleeding that is associated with acquired type 2A von Willebrand syndrome . However, the prevalence & cause of the haemostatic abnormality in aortic Stenosis are unknown .
We enrolled 50 consecutive patients with aortic Stenosis, who completed a standardized screening questionnaire to detect a H/O bleeding. 42 patients with sever aortic Stenosis underwent valve replacement.
Platelets function under conditions of high shear stress, vWf collagen-binding activity & Ag levels, & the multimeric structure of vWf were assessed @ base line & 1 day, 7 days, & six months post-operatively.
Skin or mucosal bleeding occurred in 21% of the patients with sever aortic Stenosis. Platelets-function abnormalities under condition of high shear stress, decreased vWf collagen-binding activity & the loss of the largest multimers, or a combination of these was present in 67 – 92 % of patients with sever aortic Stenosis & correlated significantly with the severity of valve Stenosis.
Type 2A vW Syndrome is common in patients with sever aortic Stenosis.
vWf abnormalities are directly related to the severity of aortic Stenosis & are improved by valve replacement in the absence of mismatch between patient & prosthesis.