Thromb Haemost 1985; 54(03): 635-638
DOI: 10.1055/s-0038-1660087
Original Article
Schattauer GmbH Stuttgart

Turnover Study of Heparin Cofactor II in Healthy Man

P Sié
The Laboratoire d’Hémostase, Centre de Transfusion Sanguine, Toulouse, France
,
D Dopouy
The Laboratoire d’Hémostase, Centre de Transfusion Sanguine, Toulouse, France
,
J Pichon
The Laboratoire d’Hémostase, Centre de Transfusion Sanguine, Toulouse, France
,
B Boneu
The Laboratoire d’Hémostase, Centre de Transfusion Sanguine, Toulouse, France
› Author Affiliations
Further Information

Publication History

Received 14 June 1985

Accepted 29 July 1985

Publication Date:
19 July 2018 (online)

Summary

Heparin cofactor II (HC II) is a heparin-dependent inhibitor of thrombin, distinct from antithrombin III (AT III). This study was designed to evaluate its metabolism in healthy subjects. Purified HC II was labelled with 125I by the lactoperoxidase-glucose oxidase technique. The biological activity of the HC II was unchanged after labelling as was its migratory pattern by crossed immunoelectrophoresis in the presence of heparin or dermatan sulfate.

Three healthy volunteers were injected with 10 uCi and the plasma radioactivity was measured daily. The data were approximated by a sum of two exponential terms and the metabolism of HC II was described by a two compartment mamillary system.

The mean values of fractional catabolic rate, intravascular fraction and half-life of the elimination phase were respectively: 0.44 d-1, 0.60 and 2.53 d. These parameters are of the same order of magnitude as those reported in the literature for AT III. The plasma HC II concentration in the 3 subjects ranged from 61 to 82 ug/ml as estimated using our purified preparation. Accordingly, the absolute catabolic rate ranged from 1.17 to 1.36 mg · kg-1 · d-1.

 
  • References

  • 1 Briginshaw GF, Shanberge JN. Identification of two distinct heparin cofactors in human plasma. Separation and partial purification. Arch Biochem Biophys 1974; 161: 683-690
  • 2 Tollefsen DM, Blank MK. Detection of a new heparin-dependent inhibitor of thrombin in human plasma. J Clin Invest 1981; 68: 589-596
  • 3 Wunderwald P, Schrenk WJ, Port H. Antithrombin BM from human plasma: an antithrombin binding moderately to heparin. Thromb Res 1982; 25: 177-191
  • 4 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
  • 5 Tollefsen DM, Pestka CA, Monfao WJ. Activation of heparin cofactor II by dermatan sulfate. J Biol Chem 1983; 258: 6713-6716
  • 6 Yamagishi R, Niwa M, Kondo SI, Sakuragawa N, Koide T. Purification and biological property of heparin cofactor II: activation of heparin cofactor II and antithrombin III by dextran sulfate and various glycosaminoglycans. Throtnb Res 1984; 36: 633-642
  • 7 Collen D, Schetz J, De Cock F, Holmer E, Verstraete M. Metabolism of antithrombin III (heparin cofactor) in man: effects of venous thrombosis and of heparin administration. Eur J Clin Invest 1977; 7: 27-35
  • 8 Scully MF, De Haas H, Chan P, Kakkar VV. Hereditary antithrombin III deficiency in an English family. Br J Haematol 1981; 47: 235-240
  • 9 Chan V, Lai CL, Chan K. Metabolism of antithrombin III in cirrhosis and carcinoma of the liver. Clin Science 1981; 60: 681-688
  • 10 Ambruso DR, Leonard BD, Bies RD, Jacobson L, Hathaway WM E, Reeve EB. Antithrombin III deficiency: decreased synthesis of a biochemically normal molecule. Blood 1982; 60: 78-83
  • 11 Swart CAM, Nijmeyer B, Andersson LO, Holmer E, Sixma JJ, Bouma BN. Elimination of intravenously administered radiolabelled antithrombin III and heparin in humans. Thromb Haemostas 1984; 52: 66-70
  • 12 Knot E, Ten Cate JW, Drijfhout HR, Kahle LH, Tytgat GN. Antithrombin III metabolism in patients with liver disease. J Clin Pathol 1984; 37: 523-530
  • 13 Sie P, Dupouy D, Pichon J, Boneu B. Constitutional heparin cofactor II deficiency associated to recurrent venous thrombosis. Lancet 1985; 2: 414-416
  • 14 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T 4. Nature 1970; 227: 680-685
  • 15 Wolf M, Boyer C, Lavergne JM, Larrieu MJ. A new familial variant of antithrombin III: antithrombin III Paris’. Br J Haematol 1982; 51: 285-295
  • 16 Matthews GM E. Theory of tracer experiments with 131I-labelled plasma proteins. Phys Med Biol 1957; 2: 36-53
  • 17 Allen TH, Peng MT, Cheng KP, Huang TF, Chang C, Fang HS. Prediction of blood volume and adiposity in man from body weight and cube of height. Metabolism 1956; 5: 328-332
  • 18 Reeve EB, Leonard B, Wentland SM, Damus P. Studies with 131I-labelled antithrombin III in dogs. Thromb Res 1980; 20: 375-389
  • 19 Reeve EB, Leonard B, Carlson T. Kinetic studies in vivo of antithrombin III. Ann NY Acad Sci 1981; 370: 680-694
  • 20 Carlson TH, Atencio AC, Simon TL. In vivo behavior of radioiodinated rabbit antithrombin III. Demonstration of a noncirculating vascular compartment. J Clin Invest 1984; 74: 191-199