Studies on the prolonged bleeding time in von Willebrand's disease

Area of Science:

• Hematology
• Vascular Biology
• Hemostasis and Thrombosis

Background:

• Von Willebrand's disease (vWd) is characterized by prolonged bleeding times.
• The precise mechanism linking factor VIII-associated properties to bleeding time in vWd remains unclear.

Purpose of the Study:

• To investigate the relationship between bleeding time and plasma levels of factor VIII procoagulant activity (VIIIAHF), factor VIII-related antigen (VIIIAGN), and Willebrand factor (VIIIVWF) in vWd patients.
• To explore the role of factor VIII in primary hemostasis at the vessel wall level.

Main Methods:

• Administration of 1-deamino-8-D-arginine vasopressin (DDAVP) to normal volunteers and vWd patients to induce endogenous factor VIII increases.
• Infusion of cryoprecipitate in vWd patients prior to dental surgery to achieve exogenous increases in factor VIII-associated properties.
• Direct immunofluorescence of gum biopsy specimens to assess VIIIAGN presence in the vessel wall.

Main Results:

• DDAVP administration increased factor VIII-associated properties in normal subjects and most vWd patients, but bleeding time remained unchanged.
• Cryoprecipitate infusion in vWd patients significantly increased VIIIAHF, VIIIAGN, and VIIIVWF, yet did not shorten bleeding time.
• Immunofluorescence showed VIIIAGN localized to venules and arterioles in moderate vWd but not in severe recessive vWd; vessel wall staining did not correlate with bleeding time correction.

Conclusions:

• Elevated plasma levels of factor VIII-associated properties do not necessarily correct the prolonged bleeding time in von Willebrand's disease.
• The study suggests that the mechanism of prolonged bleeding time in vWd may involve factors beyond plasma concentrations of factor VIII-associated properties, potentially related to vessel wall interactions.