Download PDF
Thromb Haemost 1984; 51(02): 266-268
DOI: 10.1055/s-0038-1661073
Original Article
Schattauer GmbH Stuttgart

Histidine-Rich Glycoprotein Modulates the Anticoagulant Activity of Heparin in Human Plasma

H R Lijnen
The Center for Thrombosis and Vascular Research, Department of Medical Research, University of Leuven, Belgium
,
B Van Hoef
The Center for Thrombosis and Vascular Research, Department of Medical Research, University of Leuven, Belgium
,
D Collen
The Center for Thrombosis and Vascular Research, Department of Medical Research, University of Leuven, Belgium
› Author Affiliations
Further Information

Publication History

Received 09 January 1984

Accepted 22 February 1984

Publication Date:
19 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Addition of 0.05 IU of heparin per ml normal plasma prolongs its thrombin time from 20 to 27s, but that of plasma specifically depleted in histidine-rich glycoprotein (by immunoadsorption) from 20 to 180s. Reconstitution of the depleted plasma with normal plasma or with purified histidine-rich glycoprotein normalizes its thrombin time.

In 54 plasma samples from hospitalized patients a significant negative correlation was found between the anticoagulant activity of heparin measured by thrombin inhibition and the plasma level of histidine-rich glycoprotein (r = 0.69). It is concluded that the level of histidine-rich glycoprotein modulates the anticoagulant activity of heparin in human plasma to an extent which appears to be pharmacologically and possibly clinically relevant.

Keywords

Histidine-rich glycoprotein - Heparin - Anticoagulant activity
 

  • References

  • 1 Höök M, Björk I, Hopwood J, Lindahl U. Separation of high-activity and low-activity heparin-species by affinity chromatography on immobilized antithrombin. FEBS Lett 1976; 66: 90-93
    CrossrefPubMedGoogle Scholar
  • 2 Läm LH, Silbert JE, Rosenberg RD. The separation of active and inactive forms of heparin. Biochem Biophys Res Commun 1976; 69: 570-577
    CrossrefPubMedGoogle Scholar
  • 3 Tollefsen DM, Majerus DW, Blank MK. Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma. J Biol Chem 1982; 257: 2162-2169
    PubMedGoogle Scholar
  • 4 Lijnen HR, Hoylaerts M, Collen D. Heparin binding properties of human histidine-rich glycoprotein. Mechanism and role in the neutralization of heparin in plasma J Biol Chem 1983; 258: 3803-3808
    PubMedGoogle Scholar
  • 5 Lijnen HR, Rylatt DB, Collen D. Physicochemical, immunochemical and functional comparison of human histidine-rich glycoprotein and autorosette inhibition factor. Biochim Biophys Acta 1983; 742: 109-115
    CrossrefPubMedGoogle Scholar
  • 6 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-275
    PubMedGoogle Scholar
  • 7 Tollefsen DM, Pestka CA, Monafo WJ. Activation of heparin cofactor II by dermatan sulfate. J Biol Chem. 1983 (in press)
    PubMedGoogle Scholar
  • 8 Jordan R, Beeler D, Rosenberg R. Fractionation of low molecular weight heparin species and their interaction with antithrombin. J Biol Chem 1979; 254: 2902-2913
    PubMedGoogle Scholar
  • 9 Olson ST, Shore JD. Binding of high affinity heparin to antithrombin III. Characterization of the protein fluorescence enhancement. J Biol Chem 1981; 256: 11065-11072
    PubMedGoogle Scholar
  • 10 Lijnen HR, Jacobs G, Collen D. Histidine-rich glycoprotein in a normal and a clinical population. Thromb Res 1981; 22: 519-523
    CrossrefPubMedGoogle Scholar
  • 11 Lijnen HR, Van HoefB, Collen D. Interaction of heparin with histidine-rich glycoprotein and with antithrombin III. Thromb Res 1983; 50: 560-562
    PubMedGoogle Scholar