PDF herunterladen
Thromb Haemost 1987; 57(03): 263-268
DOI: 10.1055/s-0038-1651113
Original Article
Schattauer GmbH Stuttgart

Antithrombin III and Heparin Cofactor II in Patients with Chronic Renal Failure Undergoing Regular Hemodialysis

P Toulon
1   The Laboratoire d’hématologie, UER de Biologie expérimentale et humaine, Paris, France
,
C Jacquot
2   The AURA, Paris, France
,
L Capron
3   The Centre de recherche Claude-Bernard en Pathologie vasculaire (Pr Housset), Hôpital Broussais, Paris, France
,
M -O Frydman
2   The AURA, Paris, France
,
D Vignon
4   The Poste de transfusion, Hôpital Foch, Suresnes, France
,
M Aiach
1   The Laboratoire d’hématologie, UER de Biologie expérimentale et humaine, Paris, France
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 05. Dezember 1986

Accepted after revision 10. Februar 1987

Publikationsdatum:
06. Juli 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

Heparin enhances the inhibition rate of thrombin by both antithrombin III (AT III) and heparin cofactor II (HC II). We studied the activity of these two plasma proteins in patients with chronic renal failure (CRF) undergoing regular hemodialysis as their heparin requirements varied widely. In 77 normal blood donors, normal ranges (mean ± 2 SD) were 82-122% for AT III and 65-145% for HC II. When compared with these controls 82 dialyzed CRF patients had a subnormal AT III activity and a significantly (p <0.001) lower HC II activity. To evaluate the effect of hemodialysis we compared AT III, HC II and total proteins in plasma before and after dialysis in. 24 patients (12 with normal and 12 with low basal HC II activity). AT III and HC II activities significantly (p <0.001) increased in absolute value. When related to total plasma proteins, in order to suppress the influence of hemoconcentration induced by dialysis, AT III decreased significantly (p <0.01) whereas HC II increased slightly but significantly (p <0.01) in the 12 patients with low initial HC II activity. The decrease of AT III induced by heparin administrated during dialysis is likely to account for this relative decrease of AT III activity. A modification of the distribution of both HC II and heparin between the vascular wall and the circulating blood is evoked to explain the relative increase in HC II activity and the need for higher heparin dosage in patients with low HC II levels.

Keywords

Antithrombin III - Heparin cofactor II - Chronic renal failure - Hemodialysis - Heparin
 

  • References

  • 1 Abildgaard U. Highly purified antithrombin III with heparin cofactor activity prepared by disc electrophoresis. Scand J Clin Lab Invest 1968; 21: 89-91
    CrossrefPubMedGoogle Scholar
  • 2 Yin ET, Wessler S, Stoll PJ. Identity of plasma-activated factor X inhibitor with antithrombin III and heparin cofactor. J Biol Chem 1971; 246: 3712-3719
    PubMedGoogle Scholar
  • 3 Briginshaw GF, Shanberge JN. Identification of two distinct heparin cofactors in human plasma. Arch Biochem Biophys 1974; 161: 683-690
    CrossrefPubMedGoogle Scholar
  • 4 Briginshaw GF, Shanberge JN. Identification of two distinct heparin cofactors in human plasma: II. Inhibition of thrombin and activated factor X. Thromb Res 1974; 4: 463-477
    CrossrefPubMedGoogle Scholar
  • 5 Tollefsen DM, Blank MK. Detection of a new heparin-dependent inhibitor of thrombin in human plasma. J Clin Invest 1981; 68: 589-596
    CrossrefPubMedGoogle Scholar
  • 6 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
  • 7 Wunderwald P, Schrenk WJ, Port H. Antithrombin BM from human plasma: an antithrombin binding moderately to heparin. Thromb Res 1982; 25: 177-191
    CrossrefPubMedGoogle Scholar
  • 8 Witt I, Kaiser C, Schrenk WJ, Wunderwald P. Amino acid composition and N-terminal sequence of antithrombin BM. Thromb Res 1983; 32: 513-518
    CrossrefPubMedGoogle Scholar
  • 9 Griffith MJ, Carraway T, White GC, Dombrose FA. Heparin cofactor activities in a family with hereditary antithrombin III deficiency: Evidence for a second heparin cofactor in human plasma. Blood 1983; 61: 111-118
    PubMedGoogle Scholar
  • 10 Griffith MJ. Heparin-catalyzed inhibitor/protease reactions: kinetic evidence for a common mechanism of action of heparin. Proc Natl Acad Sci USA 1983; 80: 5460-5464
    CrossrefPubMedGoogle Scholar
  • 11 Griffith MJ, Noyes CM, Church FC. Reactive site peptide structural similarity between heparin cofactor II and antithrombin III. J Biol Chem 1985; 260: 2218-2225
    PubMedGoogle Scholar
  • 12 Yin ET, Wessler S, Stoll PJ. Rabbit plasma inhibitor of the activated species of blood coagulation factor X. J Biol Chem 1971; 246: 3694-3702
    PubMedGoogle Scholar
  • 13 Rosenberg RD, Damus PS. The purification and mechanism of action of human antithrombin - heparin cofactor. J Biol Chem 1973; 248: 6490-6505
    PubMedGoogle Scholar
  • 14 Parker KA, Tollefsen DM. The protease specificity of heparin cofactor II. Inhibition of thrombin generated during coagulation. J Biol Chem 1985; 260: 3501-3505
    PubMedGoogle Scholar
  • 15 Tran TH, Marbet GA, Duckert F. Association of hereditary heparin cofactor II deficiency with thrombosis. Lancet 1985; II: 413-414
    PubMedGoogle Scholar
  • 16 Sié P, Pichon J, Dupouy D, Boneu B. Constitutional heparin cofactor II deficiency associated with recurrent thrombosis. Lancet 1985; II: 414-416
    PubMedGoogle Scholar
  • 17 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516-530
    PubMedGoogle Scholar
  • 18 Jorgensen KA, Stoffersen E. Antithrombin III in uremia. Scand J Urol Nephrol 1979; 13: 299-303
    CrossrefPubMedGoogle Scholar
  • 19 Brandt P, Jespersen J, Sorensen LH. Antithrombin-III and platelets in haemodialysis patients. Nephron 1981; 28: 1-3
    CrossrefPubMedGoogle Scholar
  • 20 Turney JH, Fewell M, Williams LC, Dodd N, Weston MJ. Paradoxical behaviour of antithrombin III during hemodialysis and its prevention with prostacyclin. Clin Nephrol 1982; 17: 31-35
    PubMedGoogle Scholar
  • 21 Jorgensen M, Eriksen HO, Tranebjoerg L. Plasma antithrombin III concentration in patients on regular haemodialysis treatment. Nephron 1985; 40: 22-24
    CrossrefPubMedGoogle Scholar
  • 22 Woo KT, Wei SS, Lee E JC, Lau YK, Lim JC. Effects of hemodialysis and peritoneal dialysis on antithrombin III and platelets. Nephron 1985; 40: 25-28
    CrossrefPubMedGoogle Scholar
  • 23 Knudsen F, Dyerberg J. Platelets and antithrombin III in uremia: the acute effect of haemodialysis. Scand J Clin Lab Invest 1985; 45: 341-347
    CrossrefPubMedGoogle Scholar
  • 24 Friberger P, Egberg N, Holmer E, Hellgren M, Blomback M. Antithrombin assay - The use of human of bovine thrombin and the observation of a “second” heparin cofactor. Thromb Res 1982; 25: 433-436
    CrossrefPubMedGoogle Scholar
  • 25 Tollefsen DM, Pestka CA, Monafo WJ. Activation of heparin cofactor II by dermatan sulfate. J Biol Chem 1983; 258: 6713-6716
    PubMedGoogle Scholar
  • 26 Tollefsen DM. Activation of heparin cofactor II by heparin and dermatan sulfate. Nouv Rev Fr Hematol 1984; 26: 233-237
    PubMedGoogle Scholar
  • 27 Kindness G, Long WF, Williamson FB. The anticoagulant activity of dermatan sulphates: evidence against the involvement of antithrombin III. Br J Pharmac 1981; 72: 81-88
    CrossrefPubMedGoogle Scholar
  • 28 Teien AN, Abildgaard U, Hook M. The anticoagulant effect of heparan sulfate and dermatan sulfate. Thromb Res 1976; 8: 859-867
    CrossrefPubMedGoogle Scholar
  • 29 Aiach M, Léon M, Michaud A, Capron L. Adaptation of synthetic peptide substrate-based assays on a discrete analyzer. Semin Thromb Hemost 1983; 9: 206-216
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 30 Abildgaard U, Lie-Larsen M. Assay of dermatan sulfate cofactor (heparin cofactor II) activity in human plasma. Thromb Res 1984; 35: 257-266
    CrossrefPubMedGoogle Scholar
  • 31 Fagerhol MK, Abildgaard U. Immunological studies on human antithrombin III. Influence of age, sex and use of oral contraceptives on serum concentration. Scand J Haematol 1970; 7: 10-17
    PubMedGoogle Scholar
  • 32 Odegard OR, Fagerhol MK, Lie M. Heparin cofactor activity and antithrombin III concentration in plasma related to age and sex. Scand J Haematol 1976; 17: 258-262
    PubMedGoogle Scholar
  • 33 Panicucci F, Sagripanti A, Conte B, Pinori E, Vispi M, Lecchini L. Antithrombin III, heparin cofactor and anticofactor Xa in relation to age, sex and pathological condition. Haemostasis 1980; 9: 297-302
    PubMedGoogle Scholar
  • 34 Tran TH, Duckert F. Heparin cofactor II determination - Levels in normals and patients with hereditary antithrombin III deficiency and disseminated intravascular coagulation. Thromb Haemostas 1984; 52: 112-116
    PubMedGoogle Scholar
  • 35 Tollefsen DM, Pestka CA. Heparin cofactor II activity in patients with disseminated intravascular coagulation and hepatic failure. Blood 1985; 66: 769-774
    PubMedGoogle Scholar
  • 36 Marciniak E, Gockerman JP. Heparin-induced decrease in antithrombin III. Lancet 1977; I: 581-584
    PubMedGoogle Scholar
  • 37 Léon M, Aiach M, Coezy E, Guennec JY, Fiessinger JN. Antithrombin III synthesis in rat liver parenchymal cells. Thromb Res 1983; 30: 369-375
    CrossrefPubMedGoogle Scholar
  • 38 Lijnen HR, Hoylaerts M, Collen D. Heparin binding properties of human HRG. Mechanism and role in the neutralization of heparin in plasma. J Biol Chem 1983; 258: 3803-3808
    PubMedGoogle Scholar
  • 39 Andersen P, Godal HC. The antiheparin effect of α1-acid glycoprotein and platelet material, evaluated by the heparin thrombin clotting time. Haemostasis 1977; 6: 339-346
    PubMedGoogle Scholar
  • 40 Handin RI, Cohen HJ. Purification and binding properties of human platelet factor 4. J Biol Chem 1976; 251: 4273-4283
    PubMedGoogle Scholar
  • 41 Sié P, Ofosu F, Fernandez F, Buchanan MR, Petitou M, Boneu B. Respective role of antithrombin III and heparin cofactor II in the in vitro anticoagulant effect of heparin and various sulphated polysaccharides. Brit J Haematol. 1986 64. (in press)
    PubMedGoogle Scholar
  • 42 Sié P, Dupouy D, Pichon J, Boneu B. Turnover study of heparin cofactor II in healthy man. Thromb Haemostas 1985; 54: 635-638
    PubMedGoogle Scholar
  • 43 Barzu T, Van Rijn J LM L, Petitou M, Molho P, Tobelem G, Caen JP. Endothelial binding sites for heparin. Biochem J. 1986 238. (in press)
    PubMedGoogle Scholar