Thromb Haemost 1965; 14(03/04): 473-489
DOI: 10.1055/s-0038-1654884
Originalarbeiten — Original Articles — Travaux Originaux
Schattauer GmbH

On the Natural Blood Coagulation Inhibitor System Investigations of Inhibitor Factors Based on Antithrombin Deficient Blood

O Egeberg
1   The Institute for Thrombosis Research, Medical Department A, University Hospital, Bikshospitalet, Oslo, Norway
› Author Affiliations
Further Information

Publication History

Publication Date:
27 June 2018 (online)

Summary

Natural coagulation inhibitor factors were studied in sera, or in fractions of sera, from patients with congenital partial deficiency of antithrombin and from normal persons. In the patients’ sera the progressive antithrombin (antithrombin III) and heparin cofactor (antithrombin II) had both been measured around 50 per cent of normal level.

No decreased activity could be demonstrated in the patients’ sera as to antiprothrombinase, the inhibitor against blood intrinsic prothrombinase activity.

For anticonvertin, the inhibitor against the tissue convertin complex, the activity was found decreased to about the same level as that demonstrated for antithrombin III and II. The results lend strong support to the hypothesis that the activities measured as anticonvertin, antithrombin III and antithrombin II represent functions of the same blood protein, which on the other side appears to be distinct from antiprothrombinase. In accordance with this explanation, an antithrombin III concentrate had also antithrombin II and anticonvertin activity, and further, adsorption of a normal human serum with convertin appeared to specifically reduce its antithrombin III activity.

The inhibitor against activated antihemophilic C factor (AHC’ = activated f. XI) was studied in sera adsorbed with BaS04 and celite. The inhibitor activity was found at normal level in the patients’ sera, consistent with the view that anti-AHC’ is distinct from antithrombin III, II and from anticonvertin. No acceleration of the anti-AHC’ activity could be demonstrated after addition to the inhibition mixture of weak solutions of heparin.

The results are discussed.

 
  • References

  • 1 Berry G. G. Antithromboplastin : The degeneration of intrinsic thromboplastin in normal serum. J. clin. Path. 11: 39 1958;
  • 2 Biggs R, Douglas A. S, MacFarlane R. G. The formation of thromboplastin in human blood. J. Physiol. (Lond) 119: 89 1953;
  • 3 Davie E. W, Ratnoff O. D. Waterfall sequence for intrinsic blood clotting. Science 145: 1310 1964;
  • 4 Deutsch E, Fuchs H. Natürlich vorkommende Koagulationsinhibitoren. Acta haemat. (Basel) 20: 97 1958;
  • 5 Deutsch E, Mammen E. The inactivation of plasma-thromboplastin. Thrombos. Diathes. haemorrh. (Stuttg) 02: 324 1958;
  • 6 Egeberg O. Assay of antihemophilic A, B and C factors by one-stage cephalin systems. Scand. J. clin. Lab. Invest. 13: 140 1961; a.
  • 7 Egeberg O. Acquired circulating anticoagulant in classical hemophilia. Scand. J. clin. Lab. Invest. 13: 535 1961; b.
  • 8 Egeberg O. The blood coagulability in diabetic patients. Scand. J .clin. Lab. Invest. 15: 533 1963;
  • 9 Egeberg O. Changes in hemostatic system associated with tendency to thrombosis. Report Xth Congr. Int. Soc. Haemat., Stockholm. 1964
  • 10 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thrombos. Diathes. haemorrh. (Stuttg) 13: 516 1965;
  • 11 Egli H, Kesselre K, Klesper R. Über die Inaktivierung von Blutthrombinase. Acta haemat. (Basel) 17: 338 1957;
  • 12 Hensen A, Loeliger E. A. Antithrombin III. Its metabolism and its function in blood coagulation. Thrombos. Diathes. haemorrh. (Stuttg) 09: 1 1963;
  • 13 Hermansky F, Vitek J. The role of proconvertin and Stuart factor in the inactivation of tissue thromboplastin by serum. Experientia 16: 455 1960;
  • 14 Hermansky F, Vitek J. Beitrag zur Problematik der Anti-Thromboplastine. Abstracts of the 8th Congr. Europ. Soc. Haemat. Wien 1961. 104 R. Spieß & Co; Wien: 1961
  • 15 Hjort P. F. Intermediate reactions in the coagulation of blood with tissue thromboplastin. Convertin, accelerin, prothrombinase. Scand. J. clin. Lab. Invest. 09. Suppl. 27 1957
  • 16 Hjort P. F, Rapaport S. I, Owren P. A. A simple one-stage prothrombin assay using Russell’s viper venom in cephalin suspension. J. Lab. clin. Med. 46: 89 1955;
  • 17 Iatridis S. G, Ferguson J. H, latridis P. G, Maudlin R. Thrombogenic properties of surface factor; evidence for an anti-surface factor activity in canine plasma. Thrombos. Diathes. haemorrh. (Stuttg) 12: 35 1964;
  • 18 Jürgens J. Factor VII-inhibitor. A new physiological serum accelerator inactivation principle. Actahaemat. (Basel) 14: 57 1955;
  • 19 Lasch H. G. Über die Hemmung von Antithrombin durch Faktor VII. Dtsch. Arch. klin. Med. 201: 671 1955;
  • 20 Lanchantin G. F, Ware A. G. Identification of a thromboplastin inhibitor in serum and in plasma. J. clin. Invest. 32: 381 1953;
  • 21 Margolis J. Glass surface blood coagulation. Nature No 4537: 10 1956;
  • 22 Margolis J. Plasma pain-producing substance and blood clotting. Nature No. 1464: 16 1957; a.
  • 23 Margolis J. Initiation of blood coagulation by glass and related surfaces. J. Physiol. 137: 95 1957; b.
  • 24 McClaughry R. I. The specificity of antithromboplastic activity. J. Mich med. Soc. 49: 685 1950;
  • 25 Morawitz P. The chemistry of blood coagulation. Charles C. Thomas; Springfield, Ill., U. S. A: 1905
  • 26 Olsson P. Variations in antithrombin activity in plasma after major surgery. Acta chir. scand. 126: 24 1963;
  • 27 Owren P. A. The coagulation of blood. Investigations on a new clotting factor. Acta med. scand. 128. Suppl. 194 1947
  • 28 Owren P. A. Le complexe activateur de la prothrombine et son intérêt clinique. Rev. Hémat. 06: 135 1951;
  • 29 Owren P. A. The present state of the converting and accelerator factors in prothrombin conversion. Int. Conference on Thrombosis and Embolism. P. 65; Schwabe & Co, Basel: 1955
  • 30 Ratnoff O. D, Davie E. W. The activation of Christmas factor (factor IX) by activated plasma thromboplastin antecedent (activated factor XI). Biochemistry 01: 677 1962;
  • 31 Ratnoff O. D, Davie W, Mallett D. L. Studies on the action of Hageman factor: Evidence that activated Hageman factor in turn activates plasma thromboplastin antecedent. J. clin. Invest. 40: 803 1961;
  • 32 Ratnoff R. D, Rosenblum J. M. Role of Hageman factor in the initiation of clotting by glass. Evidence that glass frees Hageman factor from inhibition. Amer. J. Med. 20: 160 1958;
  • 33 Schimpf K. l, Mülhäuser W, Tenpel R. La place de Tantithrombokinase tissulaire dans la coagulation sanguine. Hémostase. I: 63 1961;
  • 34 Schneider C. L. The inactivation of placental toxin by human serum. Amer. J. Physiol. 146: 140 1946;
  • 35 Seegers W. H. Prothrombin. 342 350. Harvard Univ. Press; Cambridge: 1962
  • 36 Seegers W. H, Marciniak E. Inhibition of autoprothrombin C activity with plasma. Nature 193: 1188 1962;
  • 37 Seegers W. H, Schröer H, Kagami M. Inactivation of purified autoprothrombin I with antithrombin. Canad. J. Biochem. 42: 1425 1964;
  • 38 Soulier J. P. Les inhibiteur natural de la coagulation. Sang. 30: 262 1959;
  • 39 Soulier J. P. Natural inhibitors. Progress in coagulation. 38 Schattauer, Stuttgart: 1962
  • 40 Soulier J. P, Wartelle O, Ménaché D. Hageman trait and PTA deficiency ; the role of contact of blood with glass. Brit. J. Haemat. 05: 121 1959;
  • 41 Spaet T. H, Garner E. S. Inactivation of thromboplastin in human blood. J. clin Invest. 34: 1807 1955;
  • 42 Spaet T. H, Cintron J. Induction in rabbits of activity against human blood thromboplastin. Blood 15: 772 1960;
  • 43 Spurling C. L, King PDW. Studies on thromboplastin generation. J. Lab. clin. Med. 44: 336 1954;
  • 44 Straub W, Duckert F. The formation of extrinsic prothrombin activation. Thrombos. Diathes. haemorrh. (Stuttg) 05: 402 1961;
  • 45 Thomas L. Studies on the intravascular thromboplastic effect of tissue suspensions in mice. Bull. John Hopk. Hosp. 81: 23 1947;
  • 46 Wagner R. H, Brannon Jr. WM, Brinkhous K. M. Anti-accelerator (anticonvertin) activity of canine plasma and serum fractions. Fed. Proc. 12: 405 1953;
  • 47 Wagner B. H, Brannon Jr. WM, Brinkhous K. M. Anti-accelerator (anticonvertin) activity of canine plasma and serum. Proc. Soc. exp. Biol. (N. Y) 89: 266 1955;
  • 48 Waaler B. A. Contact activation in the intrinsic blood clotting system. Scand. J. clin. Lab. Invest. 11. Suppl. 37 1959