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von Willebrand factor is not altered in azotemic dogs with prolonged bleeding time
1Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California.
Abstract:
The effects of azotemia on von Willebrand factor (vWf) plasma concentration, structure, and function were studied by utilizing canine models for both uremic bleeding and type I vWf deficiency (vWd). Seventy-five percent to 80% renal mass reduction in eight mixed-breed dogs induced marked azotemia (blood urea nitrogen [BUN] 103 +/- 7 mg/dl [mean +/- SEM]; creatinine 5.8 +/- 1 mg/dl) and prolonged mean buccal mucosal bleeding time (BMBT) from 1.8 +/- 0.2 minutes to 7.0 +/- 0.4 minutes. The mean vWf plasma concentration increased from 0.88 +/- 0.11 U/ml to 1.26 +/- 0.14 U/ml. The pre- and postsurgical sodium dodecyl sulfate-agarose gel electrophoresis multimeric patterns were similar in all dogs. Administration of cryoprecipitate from pooled azotemic mixed-breed dog plasma to five Doberman pinschers with type I vWd increased the mean plasma vWf from 0.14 +/- 0.01 U/ml to 0.48 +/- 0.04 U/ml and decreased the BMBT from 7.1 +/- 0.6 minutes to 3.14 +/- 0.09 minutes. After renal mass reduction, five type I vWd Dobermans developed marked azotemia (BUN 79 +/- 8.6 mg/dl; creatinine 3.7 +/- 0.6 mg/dl) and prolonged BMBT (16.1 +/- 3.6 minutes). Findings in the eight azotemic mixed-breed dogs indicated that (1) vWf plasma levels were normal to increased in azotemic dogs; (2) vWf structure and multimeric distribution were not altered in canine azotemia; and (3) vWf was functional when placed in a non-azotemic environment. The prolongation of the BMBT in azotemic vWd dogs indicated that factors other than alteration of vWf function were responsible for the prolonged BMBT in canine azotemia.