Bleeding is a complication of uremia that may be due, in part, to altered platelet function that can be partially attributed to changes in von Willebrand's factor (VWF). To test this hypothesis, uremic dogs and dogs with an inherited deficiency (Doberman pinschers) or complete absence (Scottish terriers) of VWF will be used. Canine VWF deficiency will be characterized by quantitating plasma and platelet von Willebrand antigen (VIII:AG) with an immunoradiometric assay. The multimeric pattern of VIII:AG from control dogs and from Doberman pinschers will be determined by SDS-agarose electrophoresis of unreduced VWF followed by detection with 125I-labeled antibodies to VIII:AG and autoradiography. Presence of VIII:AG in endothelial cells and the subendothelium and their relationship with plasma VIII:AG will be described using immunofluorescence and electron microscopic immunocytochemistry. Response of VWF deficient dogs to treatments that increase VWF in humans will be determined as will synthesis and relase of VIII:AG from cultured endothelial cells. A canine model of chronic renal failure with decrease renal mass will be developed. Uremia will be validated by routine clinical tests and hemostatic function evaluated. Bleeding times, platelet glass-bead retention and aggregation, PGI 2, and factor VIII:AG VIII:RCo and multimeric pattern will be measured. Effects of treatments to increase VWF will be evaluated. These models will be used to describe the contribution of VWF to uremic bleeding. VWF correction of uremic bleeding will be determined by treating uremic dogs with cryoprecipitate from control and VWD dogs and from VWD Doberman pinschers treated to increase plasma VWD. To determine if plasma VWF is altered in uremia and to what extent uremic bleeding can be attributed to VWF, the effectiveness of plasma and cryoprecipitate from uremic dogs in correcting the bleeding defect in VWD dogs will be determined as will the hemostatic alterations in uremic VWD dogs and their correction by addition of VWF.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037485-03
Application #
3353173
Study Section
(SRC)
Project Start
1986-09-30
Project End
1989-09-29
Budget Start
1988-09-30
Budget End
1989-09-29
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Washington State University
Department
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164