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Thromb Haemost 1992; 68(02): 136-142
DOI: 10.1055/s-0038-1656338
Original Article
Schattauer GmbH Stuttgart

The Consumption of Antithrombin III During Coagulation, Its Consequences for the Calculation of Prothrombinase Activity and the Standardisation of Heparin Activity

S Béguin
The Department of Biochemistry and Cardiovascular Research Institute at the Rijksuniversiteit Limburg, Maastricht, The Netherlands
,
H Kessels
The Department of Biochemistry and Cardiovascular Research Institute at the Rijksuniversiteit Limburg, Maastricht, The Netherlands
,
F Dol
1   Hôpital Purpan, Lab. d'Hémostase, Toulouse, France
,
H C Hemker
The Department of Biochemistry and Cardiovascular Research Institute at the Rijksuniversiteit Limburg, Maastricht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 06 January 1992

Accepted after revision 25 March 1992

Publication Date:
03 July 2018 (online)

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Summary

The decay rate of thrombin in plasma is shown to be linearly proportional to the concentration of antithrombin III (AT III), not only in the absence but also in the presence of heparin. This is a consequence of partitioning of heparin between AT III and other plasma proteins.

In previous articles we calculated the prothrombin converting activity assuming a fixed concentration of AT III. Since AT III is consumed during the clotting process, prothrombinase activity is more accurately approximated using an algorithm that counts with the decrease of the AT III concentration. It is shown this leads to higher prothrombinase activities. The (absence of) inhibition of prothrombin conversion by prothrombinase in the presence of heparins found with the previous method is also found using the new algorithm.

From the results presented it is evident that characteristic parameters of heparin action have to be normalised to the AT III concentration. On this basis we define a Standard Independent Unit of the antithrombin activity of heparin.

 

  • References

  • 1 Hemker HC, Willems GM, Béguin SA. A computer assisted method to obtain the prothrombin activation velocity in whole plasma independent of thrombin decay processes. Thromb Haemostas 1986; 56: 9-17
    PubMedGoogle Scholar
  • 2 Béguin S, Lindhout T, Hemker HC. The mode of action of heparin in plasma. Thromb Haemostas 1988; 60: 457-462
    PubMedGoogle Scholar
  • 3 Tollefsen DM. Activation of heparin cofactor II by heparin and dermatan sulfate. N Rev Fr Hematol 1984; 26: 233-237
    PubMedGoogle Scholar
  • 4 Hensen A, Loeliger EA. Antithrombin III, its metabolism and its function in blood coagulation. Thromb Haemostas 1963 Suppl 1
    PubMedGoogle Scholar
  • 5 Fagerhol MK, Abilgaard U. Immunological studies on human antithrombin III. Influence of age, sex and use of oral anticonceptives on serum concentration. Scand J Haematol 1970; 7: 10-17
    PubMedGoogle Scholar
  • 6 Nesheim ME. A simple rate law that describes the kinetics of the heparin catalysed reaction between antithrombin III and thrombin. J Biol Chem 1982; 258: 14708-14717
    PubMedGoogle Scholar
  • 7 Griffith MJ. Kinetics of the heparin-enhanced antithrombin III-thrombin reaction. Evidence for a template model for the mechanism of action of heparin. J Biol Chem 1982; 257: 7360-7365
    PubMedGoogle Scholar
  • 8 Griffith MJ. The heparin enhanced antithrombin III-thrombin reaction is saturable with respect to both antithrombin III and thrombin. J Biol Chem 1982; 257: 13899-902
    PubMedGoogle Scholar
  • 9 Schoen P, Wielders S, Petitou M, Lindhout T. The effect of sulfation on the anticoagulant and antithrombin III-binding properties of a heparin fraction with low affinity for antithrombin III. Thromb Haemostas 1990; 57: 415-423
    PubMedGoogle Scholar
  • 10 Schoen P, Lindhout T. The in situ inhibition of prothrombinase-formed human α-thrombin and meizothrombin(des fragment 1) by antithrombin III and heparin. J Biol Chem 1987; 262: 11268-11274
    PubMedGoogle Scholar
  • 11 Josso F, Prou-Wartelle O. Exploration de l'hémostase. Techniques en Hématologie Flammarion; Paris: 1972: 101-108
    Google Scholar
  • 12 Owren P, Aas K. The control of dicumarol therapy and the quantitative determination of prothrombin and proconvertin. Scand J Clin Lab Invest 1951; 3: 201-218
    CrossrefPubMedGoogle Scholar
  • 13 Preissner KT, Jenne D. Structure of vitronectin and its biological role in haemostasis. Thromb Haemostas 1991; 66: 123-132
    PubMedGoogle Scholar
  • 14 Olson TS, Shore JD. Transient kinetics of heparin-catalyzed protease inactivation by antithrombin III. The reaction step limiting heparin turnover in thrombin neutralization. J Biol Chem 1986; 261: 13151-13159
    PubMedGoogle Scholar
  • 15 Lijnen HR, Hoylaerts M, Collen D. Heparin binding properties of human histidin-rich glycoprotein. Mechanism and role in the neutralisation of heparin in plasma. J Biol Chem 1983; 258: 3803-3808
    PubMedGoogle Scholar
  • 16 Lijnen HR, van Hoef B, Collen D. Histidin-rich glycoprotein modulates the anticoagulant activity of heparin in human plasma. Thromb Haemostas 1984; 51: 266-268
    PubMedGoogle Scholar
  • 17 Lane DA, Pejler G, Flynn AM, Thomson EA, Lindahl U. Neutralisation of heparin related saccharides by histidin-rich glycoprotein and platelet factor 4. J Biol Chem 1986; 261: 7387-7392
    PubMedGoogle Scholar
  • 18 Hemker HC, Béguin S. The mode of action of heparins in plasma in vivo and in vitro. In: Heparin and related polysaccharides. Plenum Publishing Corporation; 1992: 221-230
    Google Scholar