Kinetic Analysis of Bovine Factor VIII in the Hemophilic Dog

Patricia A Gentry; Edward P Kirby; Rodney D Gentry

doi:10.1055/s-0038-1653393

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1981; 46(02): 485-488
DOI: 10.1055/s-0038-1653393

Original Article

Schattauer GmbH Stuttgart

Kinetic Analysis of Bovine Factor VIII in the Hemophilic Dog

Authors

Patricia A Gentry

The Depts. of Biomedical Sciences and of Mathematics and Statistics, University of Guelph, Guelph, Ontario, Canada and Dept, of Biochemistry and Thrombosis Research Center, Temple University Health Sciences Center, School of Medicine, Philadelphia, Pennsylvania, U.S.A.
Edward P Kirby

The Depts. of Biomedical Sciences and of Mathematics and Statistics, University of Guelph, Guelph, Ontario, Canada and Dept, of Biochemistry and Thrombosis Research Center, Temple University Health Sciences Center, School of Medicine, Philadelphia, Pennsylvania, U.S.A.
Rodney D Gentry

The Depts. of Biomedical Sciences and of Mathematics and Statistics, University of Guelph, Guelph, Ontario, Canada and Dept, of Biochemistry and Thrombosis Research Center, Temple University Health Sciences Center, School of Medicine, Philadelphia, Pennsylvania, U.S.A.

Abstract

PDF Download

Summary

Bovine factor VIII, which did not contain platelet aggregating factor activity, was infused into hemophilic dogs. Factor VIII procoagulant (VIII: C) levels in the dogs increased dramatically, then decreased in a biphasic manner. The half-life of the longest component was 3-7 hrs. The infusions were hemostatically effective and also caused a prolonged shortening of the activated partial thromboplastin time. These studies demonstrate that the platelet aggregating factor activity of bovine factor VIII is not essential for its maintenance in the circulation and that preparations lacking this activity may be clinically useful. When concentrates of partially purified factor VIII: C (essentially free of both platelet aggregating factor and factor VIII-related antigen) were infused, marked increases in VIII: C levels were also observed, but the half-life was significantly shorter (T_1/2 of approximately 1 hr).

Keywords

Factor VIII - Factor VIII turnover - Bovine - Dog - Hemophilia

PDF (302 kb)

References

References
1 Owen WG, Wagner RH. Antihemophilic factor: Separation of an active fragment following dissociation by salts or detergents. Thromb Diath Haem 1972; 27: 502-515
2 Koutts J, Stott L, Sawers RJ, Firkin BG. Variant patterns in von Willebrand’s disease. Thromb Res 1972; 5: 557-564
3 Kirby EP. Characterization of a form of bovine Factor VIII which does not aggregate human platelets. Thromb Haemostas 1981; 46: 479-484
4 Macfarlane RG, Biggs R, Bidwell E. Bovine antihaemophilic globulin in the treatment of haemophilia. Lancet 1954; 01: 1316
5 Dodds WJ. Hereditary and acquired hemorrhagic disorders in animals. Progress in Hemostasis and Thrombosis 1974; 2: 215-247
6 Gentry PA, Johnstone IB, Sanford SW. Diagnosis of classic hemophilia (hemophilia A) in a standard poodle. Canad Vet J 1977; 18: 79-81
7 Benn DM, Gentry PA, Johnstone IB. Classic hemophilia (hemophilia A) in a family of collies. Canad Vet J 1978; 19: 221-225
8 Legaz ME, Schmer G, Counts RB, Davie EW. Isolation and characterization of human Factor VIII (Antihemophilic Factor). J Biol Chem 1973; 248: 3946-3955
9 Bouma BN, Dodds WJ, van Mourik JA, Sixma JJ, Webster WP. Infusion of human and canine Factor VIII in dogs with von Willebrand disease. Scand J Haem 1976; 17: 263-275
10 Thompson AR, Forrey AW, Gentry PA, Smith KJ, Harker LA. Human factor IX in animals: Kinetics from isolation, radiolabeled protein and platelet destruction following crude concentrate infusions. Brit J Haemat 1980; 45: 329-342
11 Laurell C-B. Antigen-antibody crossed electrophoresis. Anal Biochem 1965; 10: 358-361
12 Johnson AJ, MacDonald VE, Semar M, Fields JE, Schuck J, Lewis C, Blind J. Preparation of the major plasma fractions by solid-phase polyelectrolytes. J Lab Clin Med 1978; 92: 194-210
13 More JJ. The Levenberg-Marquardt Algorithm: Implementation and Theory. In Numerical Analysis, Proceedings, Biennial Conference, Dundee 1977. ed. by Watson GA. Springer-Verlag; New York: 1978. pp 105-116
14 Golub GH, Pereyra V. The differentiation of pseudo-inverses and nonlinear least squares problems whose variables separate. SIAM J Numer Anal 1973; 10: 413-432
15 Brinkous KM, Thomas BD, Ibrahim SA, Read MS. Plasma levels of platelet aggregating factor/von Willebrand factor in various species. Thromb Res 1977; 11: 345-355
16 Vehar GA, Davie EW. Preparation and Properties of Bovine Factor VIII (Antihemophilic Factor). Biochem 1980; 19: 401-410
17 Biggs R, Denson KW E. The fate of prothrombin and Factor VIII, IX and X transfused to patients deficient in these factors. Brit J Haematol 1963; 9: 532-547
18 Pool JG, Shannon AE. Production of high potency concentrates of anti-hemophilic globulin in a closed-bag system: Assay in vitro and in vivo. N Eng J Med 1965; 273: 1443-1447
19 Bennett B, Ratnoff OD. Studies on the responses of patients with classic hemophilia to transfusions with concentrates of antihemophilic factor. J Clin Invest 1972; 51: 2593-2595
20 Sheppard CW, Uffer MB, Merker PC, Halikas G. Circulation and recirculation of injected dye in the anesthetized dog. J Appl Physiol 1968; 25: 610-618
21 Handbook of Physiology, Circulation Section 2. American Physiology Society. 1963 Volume 02.
22 Sodetz JM, Pizzo SV, McKee PA. Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein. J Biol Chem 1977; 252: 5538-5546
23 Aufderheide AW H, Skinner SF, Kaneko JJ. Clearance of cryoprecipitated Factor VIII in canine hemophilia A. Am J Vet Res 1975; 36: 367-370
24 Allain JP, Cooper HA, Wagner RH. Disappearance of canine small active Factor VIII fragment following transfusion in hemophilic dogs. Thromb Diath Haem 1975; 34: 607-608
25 Weiss HG, Sussman II, Hoyer LW. Stabilization of Factor VIII in plasma by the von Willebrand Factor. J Clin Invest 1977; 60: 390-404