Thromb Haemost 1962; 08(01): 001-020
DOI: 10.1055/s-0038-1655408
Originalarbeiten — Original Articles — Travaux Originaux
Schattauer GmbH

Autoprothrombin C in Irregular Blood Clotting[*]

Walter H. Seegers
1   Department of Physiology and Pharmacology Wayne State University, College of Medicine, Detroit, Michigan, USA
,
Eva Marciniak**
1   Department of Physiology and Pharmacology Wayne State University, College of Medicine, Detroit, Michigan, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
14 May 2019 (online)

Summary

In this study autoprothrombin C was considered in relationship to the hemorrhagic diseases. Concentrates of autoprothrombin C were made from purified prothrombin known to be homogeneous by several criteria. These autoprothrombin C preparations were free of thrombin, and were almost a single component when analyzed by centrifugation. Autoprothrombin C corrected the partial thromboplastin time and produced prothrombin consumption in all the plasmas obtained from patients with hemorrhagic diseases except parahemophilia. In the case of hemophilia B prothrombin consumption was obtained with the addition of purified prothrombin or purified autoprothrombin II. In the case of Stuart plasma prothrombin consumption was rapid after the addition of purified prothrombin or purified prothrombin chromatographed on Amberlite ICR-50, but not after the addition of purified prothrombin that was chromatographed on DEAE cellulose. The latter prothrombin is an abnormal prothrombin molecule and does not readily yield autoprothrombin C. It is concluded that Stuart prothrombin is abnormal and that this is a molecular disease. There is no need to postulate the existence of factor X to account for the irregular prothrombin activation in Stuart plasma. The most important question considered was how can autoprothrombin C be generated from prothrombin to promote the autocatalytic activation of prothrombin. Certain prothrombin molecules do not yield this enzyme, but normal prothrombin does. However, it does so only under certain conditions of activation. By applying the new knowledge of prothrombin chemistry to blood clotting irregularities in hemorrhagic diseases the following main considerations highlight the common deviations: 1. Abnormal prothrombin molecule, 2. Changes related to the derivatives of prothrombin, 3. Accessories needed for the generation of autoprothrombin C so it can function in auto-catalysis are irregular, and 4. Accessories needed for the function of autoprothrombin C after it is out of the prothrombin molecule are irregular. In the first group is Stuart Plasma. In the second group falls hemophilia B (autoprothrombin II) and the so-called factor VII deficiency (autoprothrombin I). In the third group is hemophilia A. In the fourth group is parahemophilia, and the platelet abnormalities.

* This investigation was supported by a research grant H-5141 from the National Heart Institute, National Institutes of Health, U.S. Public Health Service.


** Rockefeller Foundation Research Fellow.


 
  • References

  • 1 Seegers W. H, Alkjaersig N. Comparative Properties of Purified Human and Bovine Prothrombin.. Amer. J. Physiol. 1953; 172: 731
  • 2 Seegers W. H. The Purification of Prothrombin.. Rec. Chem. Progress 1952; 13: 143
  • 3 Seegers W. H. Prothrombin.. Havard University Press; Cambridge, Massachusetts: 1962
  • 4 Marciniak E, Seegers W. H. Autoprothrombin C: A Second Enzyme from Prothrombin.. Canad. J. Biochem. and Physiol. 1962; 40: 597
  • 5 Miller K. D. Chromatographic Isolation of Plasma Prothrombin and Trans-a-gluco-sylase.. J. Biol. Chem. 1958; 231: 987
  • 6 Seegers W. H, Landaburu R. H. Purification of Prothrombin and Thrombin by Chromatography on Cellulose.. Canad. J. Biochem. and Physiol. 1960; 38: 1405
  • 7 Seegers W. H, Levine W. G, Shepard R. S. Further Studies on the Purification of Thrombin.. Canad. J. Biochem. and Physiol. 1958; 36: 603
  • 8 Mammen E. F, Thomas W. R, Seegers W. H. Activation of Purified Prothrombin to Autoprothrombin I or Autoprothrombin II (Platelet Cofactor II) or Autoprothrombin II-A.. Thrombos. Diathes. haemorrh. 1960; 5: 218
  • 9 Harmison C. R, Seegers W. H. Some Physicochemical Properties of Bovine Autoprothrombin II.. J. Biol. Chem. in press 1962
  • 10 Ware A. G, Seegers W. H. Two-stage Procedure for the Quantitative Determination of Prothrombin Concentration.. Amer. J. Clin. Path. 1949; 19: 471
  • 11 Seegers W. H, Smith H. P. Factors which Influence the Activity of Purified Thrombin.. Amer. J. Physiol. 1942; 137: 348
  • 12 Langdell R. D, Wagner R. H, Brinkhous K. M. Effect of Antihemophilic Factor on One-stage Clotting Test. A Presumptive Test for Hemophilia and A Simple One-stage Antihemophilic Factor Assay Procedure.. J. Lab. Clin. Med. 1953; 41: 637
  • 13 Brinkhous K. M. A Study of the Clotting Defect in Hemophilia: The Delayed Formation of Thrombin.. Amer. J. Med. Sci. 1939; 198: 509
  • 14 Hougie C, Barrow E. M, Graham J. B. Stuart Clotting Defect. I. Segregation of a Hereditary Hemorrhagic State from the Heterogeneous Group Heretofore Called “Stable Factor” (SPCA, Proconvertin, Factor VII) Deficiency.. J. Clin. Invest. 1957; 36: 485
  • 15 Kowarzyk H, Marciniak E, Czerwinska B. Factor V and Autoprothrombin C.. Arch. Immun. i Terapii Dosw. 1961; 9: 719
  • 16 Owren P. A. Parahemophilia: Hemorrhagic Diathesis Due to Absence of a Previously Unknown Clotting Factor.. Lancet 1947; 1: 446
  • 17 Kowarzyk H, Marciniak E. The Significance of Prothrombin Derivatives Proceedings of the Eighth Congress of the European Society of Haematology. Vienna 1961: 402
  • 18 Kowarzyk H, Marciniak E. Trombinogeneza.. Pol. Tyg. Lek. 1961; 16: 1641
  • 19 Marciniak E. Autoprothrombin Activation in Serum.. Bull. Acad. Polon. Sci. 1961; 9: 381
  • 20 Thomas W. R, Seegers W. H. Terminal Amino Acids of Bovine Prothrombin and Thrombin Preparations.. Biochim. Biophys. Acta 1960; 42: 556
  • 21 Warner E. D, Brinkhous K. M, Smith H. P. A Quantitative Study on Blood Clotting: Prothrombin Fluctuations Under Experimental Conditions.. Amer. J. Physiol. 1936; 114: 667
  • 22 Seegers W. H, Alkjaersig N, Johnson S. A. On the Nature of the Blood Coagulation Mechanisms in Certain Clinical States.. Amer.J. Clin. Path. 1955; 25: 983