The Potential Use of Chromogenic Assays in the Routine Monitoring of Oral Anticoagulant Therapy

  • R. M. Bertina
  • E. A. Loeliger
Part of the Developments in Hematology book series (DIHI, volume 1)


The treatment of patients with oral anticoagulants proceeds in two phases. After an initial loading dose of anticoagulant the plasma concentration of the factors VII, IX, X and II decreases each according to its own half life (1–3). This is schematically illustrated in Figure 1. The factor VII activity rapidly disappears from the plasma, while the half life of factor II is about 10 times higher. After this loading dose, anticoagulant administration is gradually decreased until a maintenance dose is reached that result in the desired level of anticoagulation. In these so-called stabilized patients the administrations of the anticoagulant is such that the percentage of inhibition of the synthesis of procoagulant factors VII, II, IX and X is virtually the same for each factor (4).


Chromogenic Substrate Spectrophotometric Assay Oral Anticoagulant Therapy Chromogenic Assay Adequate Monitoring 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hellemans J, Vorlat M, and Verstraete M. 1963. Survival time of prothrombin and factors VII, IX and X after completely synthesis blocking doses of coumarin derivatives. Brit. J.Haemat. 9, 506–512.PubMedCrossRefGoogle Scholar
  2. 2.
    Hjort PF, Egeberg O, and Mikkelsen S. 1961. Turnover of prothrombin, factor VII and factor IX in a patient with haemophilia A. Scand.J.Clin.Lab. Invest. 13, 668–672.PubMedCrossRefGoogle Scholar
  3. 3.
    Kazmier FJ, Spittell JA, Thompson JJ, and Owen CA. 1965. Effect of oral anticoagulants on factors VII, IX, X and II. Arch. Intern. Med. 115, 667–673.PubMedGoogle Scholar
  4. 4.
    Loeliger EA, Esch B van der, Mattern MJ, and Brabander ASA den. 1963. Behaviour of factors II, VII, IX, and X during longterm treatment with coumarin. Thromb.Diath.Haemorrh. 9, 74–89.PubMedGoogle Scholar
  5. 5.
    Stockley IH. 1973. Interactions with oral anticoagulants–Part I.Pharmaceut.J. 210, 339–343.Google Scholar
  6. 6.
    Stockley IH. 1973. Interactions with oral anticoagulants–Part II.Pharmaceut.J. 210, 395–399.Google Scholar
  7. 7.
    Marder VJ and Shulman NR. 1964. Clinical aspects of congenital factor VII deficiency. Amer.J.Med. 37, 182–194.PubMedCrossRefGoogle Scholar
  8. 8.
    Amstel WJ van, Boekhout-Mussert MJ, and Loeliger EA. 1978. Successful prevention of coumarin-induced hemorrhagic skin necrosis by timely administration of vitamin K -1. Blut 36, 89– 93.PubMedCrossRefGoogle Scholar
  9. 9.
    Axelsson G, Korsan-Bengtsen K, and Waldenstrom J. 1976. Prothrombin determination by means of a chromogenic peptide substrate. Thromb.Haemostas. 36, 517–524.Google Scholar
  10. 10.
    Bergström K and Egberg N. 1978. Determination of vitamin K sensitive coagulation factors in plasma. Studies on three methods using synthetic chromogenic substrates. Thromb.Res. 12, 531–547.PubMedCrossRefGoogle Scholar
  11. 11.
    Kirchhof BR J, Muller AD, Vermeer C, and Hemker HC. 1979. Control of anticoagulant therapy with a chromogenic substrate. Haemostasis 8, 1–7.PubMedGoogle Scholar
  12. 12.
    Lämmle B, Eichlisberger R, Hänni L, Bounameaux H, Marbet GA, and Duckert F. 1979. Kontrolle der oralen Antikoagulation: Vergleich zwischen Quick- und kolorimetrischer Factor-X-Bestimmung bei 107 Patiënten. Schweiz.Med.Wschr. 109, 1115–1119.PubMedGoogle Scholar
  13. 13.
    Mibashan RS, Scully MF, Birch AJ, Thumpston J, MacGregor IR, and Kakkar VV. 1979. Automated control of coumarin therapy by chromogenic factor X assay. Thromb.Haemostas. 42, 291.Google Scholar
  14. 14.
    Witt I. 1977. Determination of plasma prothrombin with chromozym TH. In: Witt I (Ed), New methods for the analysis of coagulation using chromogenic substrates. Walter De Gruyter, Berlin- New York, pp. 155–169.Google Scholar
  15. 15.
    Róka L, Koch R, and Bleyl H. 1977. Studies on the determination of prothrombin with S-2160. In: Witt I (Ed), New methods for the analysis of coagulation using chromogenic substrates. Walter De Gruyter, Berlin-New York, pp 171–179.Google Scholar
  16. 16.
    Baughan DJ and Lytwyn A. 1979. A novel chromogenic assay equivalent to the one stage prothrombin time (PT). Thromb.Haemostas. 42, 291.Google Scholar
  17. 17.
    Kirchhof BR J, Vermeer C, and Hemker HC. 1978. The determination of prothrombin using synthetic chromogenic substrates; choice of a suitable activator. Thromb.Res. 13, 219–232.PubMedCrossRefGoogle Scholar
  18. 18.
    Bertina RM, Marel-van Nieuwkoop W van der, Loeliger EA. 1979. Spectrophotometric assays of prothrombin in plasma of patients using oral anticoagulants. Thromb.Haemostas. 72, 1296–1305.Google Scholar
  19. 19.
    Lindhout MJ, Kop-Klaassen BHM, and Hemker HC. 1978. Activation of decarboxyfactor X by a protein from Russell’s Viper Venom. Purification and partial characterization of activated decarboxyfactor X. Biochim.Biophys.Acta 533, 327–341.PubMedGoogle Scholar
  20. 20.
    WHO Expert Committee on Biological Standardisation. 1977. 28th Report. Technical Report Series World Health Organisation, no 610, p. 48.Google Scholar

Copyright information

© Martinus Nijhoff Publishers bv, The Hague 1980

Authors and Affiliations

  • R. M. Bertina
    • 1
  • E. A. Loeliger
    • 1
  1. 1.Hemostasis and Thrombosis Research Unit, Department of MedicineUniversity Hospital LeidenLeidenThe Netherlands

Personalised recommendations