PATHOPHYSIOLOGY

Von Willebrand factor (vWF)-

glycoprotein produced in endothelial cells and megakaryocytes that is responsible for facilitating platelet binding after injury of the endothelial surface occurs.

Von Willebrand disease

• is a common congenital bleeding disorder in which there is a deficiency or dysfunction of vWF. Factor VIII levels can be affected as well.

• The disease presents similarly to that of a platelet abnormality and can exhibit variable clinical symptomatology from mild mucocutaneous bleeding of the nose or gingiva or menorrhagia to hemarthrosis in more severe cases.

Type I

• is the most common, representing 60 to 80% of cases, a heterozygous deficiency in which there may be only 20% to 40% of normal levels of vWF in addition to a reduction in Factor VIII levels.

• (Easy bruising, mucosal bleeding or menorrhagia).

• Medications which inhibit prostaglandin and thromboxane synthesis may significantly exacerbate symptoms and can often aid in initial diagnosis.

• Type 2

• is less common, representing approximately 17% of the reported cases,

• characterized by a qualitatively abnormal vWF which can also be associated with thrombocytopenia and decreased Factor VIII.

Type 2A

lacks a normal vWF multimer because of abnormal proteolysis or reduced secretion of the factor.

Type 2B

• is a mutation which causes the vWF to be hyperactive and have an increased binding affinity to platelets c

• resulting in thrombocytopenia.

Type 2M

possesses a decreased platelet binding ability to vWF with depleted factor levels

Type 2N

exhibits a decrease in binding of vWF to Factor VIII.

Type 3

• is the rarest and the most severe form of the disease representing approximately 3% of the cases,

• where there are markedly diminished levels of vWF and FVIII.