Thromb Haemost 1979; 42(03): 1022-1032
DOI: 10.1055/s-0038-1656993
Original Article
Schattauer GmbH Stuttgart

Studies on the Thrombogenic Activities in Two Prothrombin Complex Concentrates

Ulla Hedner
The Coagulation Laboratory, University of Lund, Allmänna Sjukhuset, Malmö, Sweden
,
Inga Marie Nilsson
The Coagulation Laboratory, University of Lund, Allmänna Sjukhuset, Malmö, Sweden
,
Sven-Erik Bergentz
The Coagulation Laboratory, University of Lund, Allmänna Sjukhuset, Malmö, Sweden
› Institutsangaben
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Publikationsverlauf

Received 13. August 1978

Accepted 16. März 1979

Publikationsdatum:
23. August 2018 (online)

Summary

The effect on the coagulation and fibrinolytic systems of various factor IX concentrates after addition of heparin, antithrombin III or Trasylol to the concentrate before infusion into dogs was studied in an attempt to characterize the clot-promoting activity or activities in these concentrates. After infusion of Preconativ (AB Kabi; 100 u factor IX/kg bodyweight) only small decreases of fibrinogen and platelet count in the samples taken 1 and 4 hrs after infusion were found. Addition of heparin (10 u/ml; 5 dogs) or Trasylol (40 u/u factor IX initially followed by 10,000 u/h; 3 dogs) had no effect but addition of antithrombin III (100 u/kg; 3 dogs) prevented all changes. Infusion of Konyne (Cutter Laboratories; 100 u/kg bodyweight) induced marked decreases of both fibrinogen and the platelet count at 1, 4 and 24 hrs after infusion and the ethanol gelation test became positive. Addition of heparin (10 u/ml; 5 dogs) diminished the changes but did not completely counteract them. Antithrombin III (100 u/kg; 3 dogs) added to the concentrate before infusion also reduced the induced changes to about the same extent as heparin. Trasylol (40 u/u factor IX initially followed by 10,000 u/h; 3 dogs) did not seem to have any effect. Addition of both antithrombin III and Trasylol (4 dogs) did, however, prevent almost all changes.

It is thus obvious that the two commercial factor IX concentrates used may contain clot promoting activities and that these activities may differ between various concentrates.

 
  • References

  • 1 Blatt PM, Lundblad RL, Kingdon HS, McLean G, Roberts HR. 1974; Thrombogenic materials in prothrombin complex concentrates. Annals of Internal Medicine 81: 766
  • 2 Cederbaum AI, Blatt PM, Roberts H. 1976; Intravascular coagulation with use of human prothrombin complex concentrates. Annals of Internal Medicine 84: 683
  • 3 Cederbaum AI, Roberts HR. 1973; Complications of the use of prothrombin complex concentrates in liver disease. Clinical Research 21: 92
  • 4 Elsinger F. 1977; Feiba Immuno. A preparation with factor eight inhibitor bypassing activity Thrombosis and Haemostasis 38: 346 (abstr.)
  • 5 Fagerhol MK, Abildgaard U. 1970; Immunological studies on human antithrombin III. Influence of age, sex and use of oral contraceptives on serum concentration Scandinavian Journal of Haematology 7: 10
  • 6 Ganrot PO. 1966; Determination of α2-macroglobulin as trypsinprotein esterase. Clinica Chimica Acta 14: 493
  • 7 Godal HC, Abildgaard U, Kierulf P. 1971; Ethanol gelation and fibrin monomers in plasma. Scandinavian Journal of Haematology Suppl 13: 189
  • 8 Hedner U, Nilsson IM, Bergentz S-E. 1976; Various prothrombin complex concentrates and their effect on coagulation and fibrinolysis in vivo. Thrombosis and Haemostasis 35: 386
  • 9 Kasper CK. 1973; Postoperative thrombosis in haemophilia B. New England Journal of Medicine 289: 160
  • 10 Kingdon HS, Lundblad RL, Veltkamp JJ, Aronson DL. 1975 Potentially thrombogenic materials in factor IX concentrates. Thrombosis et Diathesis Haemorrhagica (Stuttg.).
  • 11 Kurachi K, Fujikawa K, Schmer G, Davie EW. 1976; Inhibition of bovine factor IXa and factor Xaβ by antithrombin III. Biochemistry 15: 373
  • 12 Latallo ZS, Wegrzynowicz E, Teisseyre E, Kopec M. 1970; Simple and rapid evaluation of the intravascular coagulation and fibrinolytic status by application of protamine sulphate and Reptilase. Scandinavian Journal of Haematology, Suppl 13: 387
  • 13 Leandoer L, Bergentz S-E, Nilsson IM. 1968; Coagulation factors and components of the fibrinolytic system in lymph and blood in dogs. Thrombosis et Diathesis Haemorrhagica 19: 129
  • 14 MéNaché D, Guillin MC. 1975; The use of factor IX concentrates for patients with conditions other than factor IX deficiency. British Journal of Haematology Suppl 31: 247
  • 15 Miller-Andersson M, BORG H, Andersson L-O. 1974; Purification of antithrombin III by affinity chromatography. Thrombosis Research 5: 439
  • 16 Niléhn J-E. 1967; Separation and estimation of “split products” of fibrinogen and fibrin in human serum. Thrombosis et Diathesis Haemorrhagica 18: 487
  • 17 Nilsson IM. 1974. Haemorrhagic and Thrombotic Diseases. John Wiley & Sons, Ltd; London: 1974
  • 18 Nilsson IM, Ahlberg A, Bjorlin G. 1971; Clinical experience with a Swedish factor IX concentrate. Acta Medica Scandinavica 190: 257
  • 19 Nilsson IM, Hedner U, Ahlberg A, Larsson SA, Bergentz S-E. 1977; Surgery of hemophiliacs - 20 years experience. World Journal of Surgery 1: 55
  • 20 Nilsson IM, Hedner U, Bjorlin G. 1973; Suppression of factor IX antibody in hemophilia B by factor IX and cyclophosphamide. Annals of Internal Medicine 78: 91
  • 21 Nilsson IM, Olow B. 1962; Determination of fibrinogen and fibrinogenolytic activity. Thrombosis et Diathesis Haemorrhagica 8: 297
  • 22 Paraskevas M, Nilsson IM, Martinsson G. 1962; A method for determining serum inhibitors of plasminogen activation. Scandinavian Journal of Clinical and Laboratory Investigation 14: 138
  • 23 Pepper DS, Banhegyi D, Howie A, Cash JD. 1977; a In vitro thrombogenicity tests of factor IX concentrates. British Journal of Haematology 36: 573
  • 24 Pepper DS, Banhegyi D, Howie A. 1977; a Spectrophotometric determination of factor Xa generation in factor IX concentrates. Thrombosis and Haemostasis 37: 535
  • 25 Sakuragawa N, Takahashi K, Hoshiyama M, Nirya K, Itoh M, Matsuoko M, Ohniski Y. 1977; Characteristics and thrombogenicity of prothrombin complex concentrates. Thrombosis Research 1: 315
  • 26 Sas G, Owens RE, Smith JK, Middleton S, Cash J. 1975; In vitro spontaneous thrombin generation in human factor IX concentrates. British Journal of Haematology 31: 25
  • 27 Smith JK, Snape TJ, Bidwell E, Edwards R, Gunson HH. 1977; Preparation of factor IX concentrate from platelet-rich plasma. Thrombosis and Haemostasis 37: 363
  • 28 Tullis JL, Melin M, Jurgian P. 1965; Clinical use of human prothrombin complexes. New England Journal of Medicine 273: 667
  • 29 Vermylen J, Schetz J, Semeraro N, Verstraete M. 1976; Clinical and laboratory experience with fraction R: Attempts at identifying the active principle. Workshop on Inhibitors of Factors VIII and IX (Facultas-Verlag, Wien), Wien, Jan. 26-26 p 110