The Turnover in Normal Dogs of Prothrombin and Its Fragments; Effect of Induced Intravascular Coagulation

Summary

When ¹²⁵I-labeled canine prothrombin was given to normal adult dogs intravenously, it was calculated that 240% of the plasma prothrombin crossed the capillary barrier per day, 410% of the interstitial prothrombin returned to the blood stream daily, and 79% of the plasmatic prothrombin was catabolized per day. These data are in close agreement with those observed for bovine prothrombin in calves by Takeda (1970).

When derived from normal dog prothrombin, prethrombin-1 is a mixture of 2 polypeptides, one larger than the other, and both present in about equal amounts. The longer peptide, “prethrombin-1-long,” was catabolized twice as fast as prothrombin, and the shorter, “prethrombin-1-short,” 4 times faster. Prothrombin fragment-1 was catabolized by the normal dog still more rapidly.

The catabolism of prothrombin was not accelerated in 3 dogs receiving continuous infusions of a thromboplastic emulsion of dog brain. Nor was the level of prothrombin in their plasma remarkably altered.

• References

• 1 Butkowski RJ. 1974. Prothrombin Activation: Studies in Purified and in Paravivo Systems. M.S. Thesis, University of Minnesota; U.S.A.:
• 2 Butkowski RJ, Bajaj SP, Mann KG. 1974; The preparation and activation of [sialyl-³H]prothrombin. Journal of Biological Chemistry 249: 6562
• 3 Cooper HA, Bowie EJ W, Didisheim PA, Owen Jr CA. 1971; Paradoxic changes in platelets and fibrinogen in chronically induced intravascular coagulation. Mayo Clinic Proceedings 46: 521
• 4 Cooper HA, Bowie EJ W, Owen Jr CA. 1973; Chronic induced intravascular coagulation in dogs. American Journal of Physiology 225: 1355
• 5 Fuster V, Bowie EJ W, Kazmier FJ, Owen Jr CA. 1974; a Plasma platelet 4-like activity reflecting rate of platelet consumption in chronically induced intravascular coagulation in dogs. Thrombosis Research 4: 241
• 6 Fuster V, Owen Jr CA, Pintado T. 1974; b Platelet kinetics and the effect of aspirin in chronically induced intravascular coagulation in dogs. Thrombosis et Diathesis Haemorrhagica suppl (Suppl. 60) 371
• 7 Greenwood FC, Hunter WM, Glover JS. 1963; The preparation of 131I-labeled human growth hormone of high specific activity. Biochemical Journal 89: 114
• 8 Hellemans J, Vorlat MA, Verstraete M. 1963; Survival time of prothrombin and factors VII, IX and X after completely synthesizing blocking doses of coumarin derivatives. British Journal of Haematology 9: 506
• 9 Jackson CM. 1977; Recommended nomenclature for blood clotting zymogens and zymogen activation products of the International Committee on Thrombosis and Haemostasis. Thrombosis and Haemostasis 38: 567
• 10 Mann KG. 1976. Prothrombin. In Lorand L. (editor) Methods in Enzymology, Volume 45, Proteolytic Enzymes (Part B). New York: Academic Press, U.S.A; p 123
• 11 Owen Jr CA, Bowie EJ W. 1974; ¹²⁵I versus⁷⁵Se labeling of fibrinogen for measuring turnover of canine fibrinogen. Proceedings of the Society for Experimental Biology and Medicine 146: 349
• 12 Owen Jr CA, Bowie EJ W. 1975; Effect of heparin on chronically induced intravascular coagulation in dogs. American Journal of Physiology 229: 449
• 13 Owen Jr CA, Bowie EJ W. 1978; Intravascular coagulation in the dog induced by means of continuous infusion of thromboplastic emulsion. Excerpta Medica International Congress Series 415: 782
• 14 Owen Jr CA, Bowie EJ W, Cooper HA. 1973; Turnover of fibrinogen and platelets in dogs undergoing induced intravascular coagulation. Thrombosis Research 2: 251
• 15 Owen Jr CA, Bowie EJ W, Didisheim P, Thompson Jr JH. 1969. Diagnosis of Bleeding Disorders, first edition. Little, Brown & Company; U.S.A: p 188
• 16 Owen Jr CA, Bowie EJ W, Thompson Jr JH. 1975. The Diagnosis of Bleeding Disorders, second edition. Little, Brown & Company; U.S.A.: Pp 85-154
• 17 Owen Jr CA, Hurn MM, Mann FD. 1955; Dextran as a substitute for acacia in assay of plasma prothrombin. American Journal of Clinical Pathology 25: 1279
• 18 Shapiro SS, Martinez J. 1969; Human prothrombin metabolism in normal man and in hypocoagulable states. Journal of Clinical Investigation 48: 1292
• 19 Sun NC J, Bowie EJ W, Titus JL, Owen Jr CA. 1974; Effect of induced chronic intravascular coagulation on plasminogen activator in dogs. Thrombosis et Diathesis Haemorrhagica 32: 189
• 20 Takeda Y. 1970; Studies of the effect of heparin, Coumadin, and vitamin K on prothrombin metabolism and distribution in calves with the use of iodine-125-prothrombin. Journal of Laboratory and Clinical Medicine 75: 355
• 21 Takeda Y. 1972; Studies of the metabolism and distribution of prothrombin in healthy men with autologous¹²⁵I-prothrombin. Thrombosis et Diathesis Haemorrhagica 27: 472
• 22 Oosterom AT Van, Mattie H, Hermens WT, Veltkamp JJ. 1976; The influence of the thyroid function on the metabolic rate of prothrombin, factor VII and factor X in the rat. Thrombosis and Haemostasis 35: 607