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Veterinary research communications1989; 13(1); 31-46; doi: 10.1007/BF00366851

Antithrombin III activity (residual thrombin activity) in plasma from non-medicated or heparinized horses.

Abstract: Two synthetic substrate assays (fluorometric and chromogenic) were used to measure antithrombin-III (AT-III) activity (residual thrombin activity) in non-medicated and heparin (sodium) treated horses. In 18 non-medicated horses the fluorometric substrate assay (FSA) values were similar to previous reports but they reflected inconsistent trends and larger deviations in the heparin-treated groups (Group 2: 40 and 100 U/kg IV, n = 6; Group 3: 240 U/kg IV, n = 5; Group 4: 80 U/kg IV followed by 160 U/kg SC, n = 8) when compared to the chromogenic substrate assay (CSA) values. The CSA values for the 18 non-medicated horses indicated a higher AT-III activity (lower residual thrombin activity) than the FSA. AT-III activity was quantified in 18 non-medicated horses (29 mg/dl) and compared well with values for humans (30 mg/dl) and dogs (40 mg/dl). Plasma heparin concentrations, determined by the FSA, correlated well with the 'therapeutic range' (1.5 fold to 2.5 fold prolongation of the activated partial thromboplastin time (APTT) normal value) and values reported for humans. The effect of heparin therapy on AT-III activity in four treatment regimens was evaluated. AT-III activity was not significantly affected (with one exception) by a single dose of intravenous (IV) heparin (40 and 100 U/kg) nor by repeated subcutaneous (SC) injections of heparin (240 U/kg). A transient increase in residual thrombin activity was measured 12 h after an intravenous (80 U/kg) injection of heparin. Large doses of heparin (80 U/kg IV followed by 160 U/kg SC) given every 12 h produced a progressive prolongation of the APTT. In this group the APTT remained prolonged 48 h after the last treatment.
Publication Date: 1989-01-01 PubMed ID: 2773304DOI: 10.1007/BF00366851Google Scholar: Lookup
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  • Comparative Study
  • Journal Article

Summary

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This study focuses on the examination of antithrombin III activity (which is reflective of residual thrombin activity) in horses that have been either non-medicated or treated with heparin. The researchers used two synthetic substrate assays to gauge this activity and found inconsistent trends in heparin-treated groups when compared to non-medicated ones. They also assessed the effects of different heparin treatments on antithrombin III activity.

Assessment of Antithrombin III Activity

  • Two synthetic substrate assays, fluorometric and chromogenic, were used to measure residual thrombin activity in non-medicated and heparin-treated horses.
  • The assays revealed similar values of AT-III activity for the non-medicated horses when compared with prior reports.
  • However, the assays showed larger deviations and inconsistent trendlines in the groups treated with heparin when compared to non-medicated groups.

Comparison of Assays

  • The chromogenic substrate assay indicated a higher AT-III activity among the non-medicated horses than the fluorometric substrate assay.
  • The AT-III activity in non-medicated horses measured via the CSA correlated well with values derived from humans and dogs.

Impact of Heparin Therapy

  • The researchers looked at the effects of four different regimes of heparin therapy on AT-III activity.
  • A single dose of intravenous heparin or regular subcutaneous injections didn’t significantly impact AT-III activity, with only one slight deviation.
  • A temporary increase in residual thrombin activity was recorded 12 hours after an injection of heparin intravenously.

Large Heparin Doses and Antithrombin III Activity

  • Higher doses of heparin administered intravenously and then subcutaneously every twelve hours resulted in a continued lengthening of the activated partial thromboplastin time (APTT).
  • In this group, the APTT remained considerably prolonged even 48 hours after the last administration of heparin discounting the temporary increase.

Cite This Article

APA
Darien BJ, Potempa J, Moore JN, Travis J. (1989). Antithrombin III activity (residual thrombin activity) in plasma from non-medicated or heparinized horses. Vet Res Commun, 13(1), 31-46. https://doi.org/10.1007/BF00366851

Publication

ISSN: 0165-7380
NlmUniqueID: 8100520
Country: Switzerland
Language: English
Volume: 13
Issue: 1
Pages: 31-46

Researcher Affiliations

Darien, B J
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602.
Potempa, J
    Moore, J N
      Travis, J

        MeSH Terms

        • Animals
        • Antithrombin III / analysis
        • Chromogenic Compounds
        • Fluorometry
        • Heparin / administration & dosage
        • Heparin / blood
        • Horses / blood
        • Injections, Intravenous / veterinary
        • Injections, Subcutaneous / veterinary
        • Partial Thromboplastin Time
        • Reference Values

        References

        This article includes 57 references
        1. Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time.. N Engl J Med 1972 Aug 17;287(7):324-7.
          pubmed: 5041701doi: 10.1056/NEJM197208172870703google scholar: lookup
        2. Murano G. The "Hageman" connection: interrelationships of blood coagulation, fibrino(geno)lysis, kinin generation, and complement activation.. Am J Hematol 1978;4(4):409-17.
          pubmed: 362910doi: 10.1002/ajh.2830040412google scholar: lookup
        3. Stephens KA, Morcom E, Hood DM. Measurement of plasma antithrombin III activity in healthy horses.. Am J Vet Res 1984 Feb;45(2):351-3.
          pubmed: 6711961
        4. Hirsh J. Mechanism of action and monitoring of anticoagulants.. Semin Thromb Hemost 1986 Jan;12(1):1-11.
          pubmed: 3961504doi: 10.1055/s-2007-1003530google scholar: lookup
        5. Hegt VN, Brakmen P. Inhibition of fibrinolysis by the human vascular wall related to the presence of smooth muscle cells.. Haemostasis 1974;3(2):118-28.
          pubmed: 4140806doi: 10.1159/000214046google scholar: lookup
        6. Messmore HL Jr. Natural inhibitors of the coagulation system.. Semin Thromb Hemost 1982 Oct;8(4):267-75.
          pubmed: 6184781doi: 10.1055/s-2007-1005057google scholar: lookup
        7. Gerhards H. [The origin of thrombophlebitis in the horse--the contribution of acquired hypercoagulability].. Dtsch Tierarztl Wochenschr 1987 Mar 9;94(3):173-4.
          pubmed: 3552574
        8. Marcum JA, Rosenberg RD. Anticoagulantly active heparin-like molecules from vascular tissue.. Biochemistry 1984 Apr 10;23(8):1730-7.
          pubmed: 6232950doi: 10.1021/bi00303a023google scholar: lookup
        9. Johnstone IB, Crane S. Hemostatic abnormalities in equine colic.. Am J Vet Res 1986 Feb;47(2):356-8.
          pubmed: 3954219
        10. Marciniak E, Gockerman JP. Kinetics of elimination of antithrombin III concentrate in heparinized patients.. Br J Haematol 1981 Aug;48(4):617-25.
        11. Hellebrekers LJ, Slappendel RJ, van den Brom WE. Effect of sodium heparin and antithrombin III concentration on activated partial thromboplastin time in the dog.. Am J Vet Res 1985 Jul;46(7):1460-2.
          pubmed: 4026027
        12. Johnstone IB, Crane S. Haemostatic abnormalities in horses with colic--their prognostic value.. Equine Vet J 1986 Jul;18(4):271-4.
        13. Nilsen DW, Brosstad F, Kierulf P, Godal HC. Binding of various thrombin fractions to fibrin and the influence of AT-III on their adsorption.. Thromb Haemost 1986 Jun 30;55(3):352-6.
          pubmed: 3750265
        14. Bachmann F, Kruithof IE. Tissue plasminogen activator: chemical and physiological aspects.. Semin Thromb Hemost 1984 Jan;10(1):6-17.
          pubmed: 6422555doi: 10.1055/s-2007-1004403google scholar: lookup
        15. Holland M, Kelly AB, Snyder JR, Steffey EP, Willits N, McNeal D. Antithrombin III activity in horses with large colon torsion.. Am J Vet Res 1986 Apr;47(4):897-900.
          pubmed: 3963594
        16. Johnstone IB, McAndrew KH, Baird JD. Early detection and successful reversal of disseminated intravascular coagulation in a thoroughbred mare presented with a history of diarrhoea and colic.. Equine Vet J 1986 Jul;18(4):337-40.
        17. Hull RD, Raskob GE, Hirsh J, Jay RM, Leclerc JR, Geerts WH, Rosenbloom D, Sackett DL, Anderson C, Harrison L. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis.. N Engl J Med 1986 Oct 30;315(18):1109-14.
          pubmed: 3531862doi: 10.1056/NEJM198610303151801google scholar: lookup
        18. BLOMBAECK B, BLOMBAECK M, OLSSON P. STUDIES ON THROMBIN INACTIVATION IN NORMAL PLASMA, SERUM AND PLASMA FRACTIONS, AND ITS RELATION TO HEPARIN.. Thromb Diath Haemorrh 1963 Jul 15;143:368-86.
          pubmed: 14081260
        19. Ofosu FA, Modi G, Cerskus AL, Hirsh J, Blajchman MA. Heparin with low affinity to antithrombin III inhibits the activation of prothrombin in normal plasma.. Thromb Res 1982 Nov 15;28(4):487-97.
          pubmed: 7164033doi: 10.1016/0049-3848(82)90165-7google scholar: lookup
        20. Travis J, Salvesen GS. Human plasma proteinase inhibitors.. Annu Rev Biochem 1983;52:655-709.
        21. Suchman AL, Griner PF. Diagnostic uses of the activated partial thromboplastin time and prothrombin time.. Ann Intern Med 1986 Jun;104(6):810-6.
          pubmed: 3706933doi: 10.7326/0003-4819-104-6-810google scholar: lookup
        22. Irwin JF, Seegers WH, Andary TJ, Fekete LF, Novoa E. Blood coagulation as a cybernetic system: control of autoprothrombin C (Factor Xa) formation.. Thromb Res 1975 May;6(5):431-41.
          pubmed: 237339doi: 10.1016/0049-3848(75)90159-0google scholar: lookup
        23. Meyers K, Reed S, Keck M, Clem M, Bayly W. Circulating endotoxin-like substance(s) and altered hemostasis in horses with gastrointestinal disorders: an interim report.. Am J Vet Res 1982 Dec;43(12):2233-8.
          pubmed: 7165171
        24. Triplett DA, Banez EI, Harms CS. Fluorogenic substrate assay of antithrombin III: a clinical study.. Thromb Res 1983 Sep 15;31(6):855-62.
          pubmed: 6417828doi: 10.1016/0049-3848(83)90116-0google scholar: lookup
        25. Ofosu FA, Gray E. Mechanisms of action of heparin: applications to the development of derivatives of heparin and heparinoids with antithrombotic properties.. Semin Thromb Hemost 1988 Jan;14(1):9-17.
          pubmed: 2451294doi: 10.1055/s-2007-1002750google scholar: lookup
        26. Björk I, Jackson CM, Jörnvall H, Lavine KK, Nordling K, Salsgiver WJ. The active site of antithrombin. Release of the same proteolytically cleaved form of the inhibitor from complexes with factor IXa, factor Xa, and thrombin.. J Biol Chem 1982 Mar 10;257(5):2406-11.
          pubmed: 6977539
        27. Nalbandian RM, Henry RL. Platelet-endothelial cell interactions. Metabolic maps of structures and actions of prostaglandins, prostacyclin, thromboxane and cyclic AMP.. Semin Thromb Hemost 1978 Fall;5(2):87-111.
          pubmed: 216078doi: 10.1055/s-0028-1087147google scholar: lookup
        28. Fareed J, Messmore HL, Walenga JM, Bermes EW, Bick RL. Laboratory evaluation of antithrombin III: a critical overview of currently available methods for antithrombin III measurements.. Semin Thromb Hemost 1982 Oct;8(4):288-301.
          pubmed: 6817417doi: 10.1055/s-2007-1005059google scholar: lookup
        29. MacHarg MA, Becht JL. The pharmacology of heparin prophylaxis.. J Am Vet Med Assoc 1983 Jul 1;183(1):129-30.
          pubmed: 6874519
        30. Gerrard JM, White JG. Prostaglandins and thromboxanes: "middlemen" modulating platelet function in hemostasis and thrombosis.. Prog Hemost Thromb 1978;4:87-125.
          pubmed: 213813
        31. Chase T Jr, Shaw E. p-Nitrophenyl-p'-guanidinobenzoate HCl: a new active site titrant for trypsin.. Biochem Biophys Res Commun 1967 Nov 30;29(4):508-14.
          pubmed: 16496527doi: 10.1016/0006-291x(67)90513-xgoogle scholar: lookup
        32. Morris DD, Beech J. Disseminated intravascular coagulation in six horses.. J Am Vet Med Assoc 1983 Nov 15;183(10):1067-72.
          pubmed: 6643211
        33. Lynch DM, Leff LK, Howe SE. Preoperative AT-III values and clinical postoperative thrombosis: a comparison of three antithrombin-III assays.. Thromb Haemost 1984 Aug 31;52(1):42-4.
          pubmed: 6495264
        34. Mitchell GA, Hudson PM, Huseby RM, Pochron SP, Gargiulo RJ. Fluorescent substrate assay for antithrombin III.. Thromb Res 1978 Feb;12(2):219-25.
          pubmed: 416516doi: 10.1016/0049-3848(78)90293-1google scholar: lookup
        35. de Swart CA, Nijmeyer B, Andersson LO, Holmer E, Sixma JJ, Bouma BN. Elimination of intravenously administered radiolabelled antithrombin III and heparin in humans.. Thromb Haemost 1984 Aug 31;52(1):66-70.
          pubmed: 6495266
        36. Chiu HM, Hirsh J, Yung WL, Regoeczi E, Gent M. Relationship between the anticoagulant and antithrombotic effects of heparin in experimental venous thrombosis.. Blood 1977 Feb;49(2):171-84.
          pubmed: 831872
        37. Goodnight SH Jr, Schaeffer JL, Sheth K. Measurement of antithrombin III in normal and pathologic states using chromogenic substrate S-2238. Comparison with immunoelectrophoretic and factor Xa inhibition assays.. Am J Clin Pathol 1980 May;73(5):639-47.
          pubmed: 7377131doi: 10.1093/ajcp/73.5.639google scholar: lookup
        38. Machovich R, Borsodi A, Blaskó G, Orakzai SA. Inactivation of alpha- and beta-thrombin by antithrombin-III, alpha 2-macroglobulin and alpha 1-proteinase inhibitor.. Biochem J 1977 Nov 1;167(2):393-8.
          pubmed: 74248doi: 10.1042/bj1670393google scholar: lookup
        39. Highsmith RF, Rosenberg RD. The inhibition of human plasmin by human antithrombin-heparin cofactor.. J Biol Chem 1974 Jul 25;249(14):4335-8.
          pubmed: 4276455
        40. Bernard W, Morris DD, Divers TJ, Ramberg C. Plasma antithrombin-III values in healthy horses: effect of sex and/or breed.. Am J Vet Res 1987 May;48(5):866-8.
          pubmed: 3592391
        41. MacGregor IR, Lane DA, Kakkar VV. The heparin-accelerated neutralisation of bovine alpha and beta thrombins by antithrombin III.. Biochim Biophys Acta 1980 Sep 17;632(1):131-7.
          pubmed: 7417517doi: 10.1016/0304-4165(80)90256-1google scholar: lookup
        42. 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 Feb;7(1):27-35.
        43. Kaplan AP. Initiation of the intrinsic coagulation and fibrinolytic pathways of man: the role of surfaces, hageman factor, prekallikrein, high molecular weight kininogen, and factor XI.. Prog Hemost Thromb 1978;4:127-75.
          pubmed: 362477
        44. Salzman EW, Deykin D, Shapiro RM, Rosenberg R. Management of heparin therapy: Controlled prospective trial.. N Engl J Med 1975 May 15;292(20):1046-50.
          pubmed: 1091856doi: 10.1056/NEJM197505152922002google scholar: lookup
        45. Björk I, Nordenman B. Acceleration of the reaction between thrombin and antithrombin III by non-stoichiometric amounts of heparin.. Eur J Biochem 1976 Sep 15;68(2):507-11.
        46. Ofosu FA, Sie P, Modi GJ, Fernandez F, Buchanan MR, Blajchman MA, Boneu B, Hirsh J. The inhibition of thrombin-dependent positive-feedback reactions is critical to the expression of the anticoagulant effect of heparin.. Biochem J 1987 Apr 15;243(2):579-88.
          pubmed: 2443128doi: 10.1042/bj2430579google scholar: lookup
        47. Sié P, Lansen J, Lacheretz F, Verschuere B, Boneu B. Comparative turn-over of heparin cofactor II and antithrombin III in baboons. Influence of heparin and pentosan polysulfate administration.. Thromb Haemost 1986 Dec 15;56(3):302-7.
          pubmed: 2436331
        48. Collen D. On the regulation and control of fibrinolysis. Edward Kowalski Memorial Lecture.. Thromb Haemost 1980 Jun 18;43(2):77-89.
          pubmed: 6450468
        49. Feldman BF, Madewell BR, O'Neill S. Disseminated intravascular coagulation: antithrombin, plasminogen, and coagulation abnormalities in 41 dogs.. J Am Vet Med Assoc 1981 Jul 15;179(2):151-4.
          pubmed: 7263467
        50. Marciniak E, Gockerman JP. Heparin-induced decrease in circulating antithrombin-III.. Lancet 1977 Sep 17;2(8038):581-4.
          pubmed: 71399doi: 10.1016/s0140-6736(77)91429-5google scholar: lookup
        51. Fey MF, Lang M, Furlan M, Beck EA. Monitoring of heparin therapy with the activated partial thromboplastin time and chromogenic substrate assays.. Thromb Haemost 1987 Oct 28;58(3):853-5.
          pubmed: 3481140
        52. Scott CF, Schapira M, James HL, Cohen AB, Colman RW. Inactivation of factor XIa by plasma protease inhibitors: predominant role of alpha 1-protease inhibitor and protective effect of high molecular weight kininogen.. J Clin Invest 1982 Apr;69(4):844-52.
          pubmed: 7076850doi: 10.1172/jci110524google scholar: lookup
        53. Tollefsen DM, Pestka CA, Monafo WJ. Activation of heparin cofactor II by dermatan sulfate.. J Biol Chem 1983 Jun 10;258(11):6713-6.
          pubmed: 6687888
        54. Johnstone IB, Blackwell TE. Disseminated intravascular coagulation in a horse with postpartum ulcerative colitis and laminitis.. Can Vet J 1984 May;25(5):195-8.
          pubmed: 17422399
        55. Gerhards H, Eberhardt C. Plasma heparin values and hemostasis in equids after subcutaneous administration of low-dose calcium heparin.. Am J Vet Res 1988 Jan;49(1):13-8.
          pubmed: 3354959
        56. Rosenberg RD, Rosenberg JS. Natural anticoagulant mechanisms.. J Clin Invest 1984 Jul;74(1):1-6.
          pubmed: 6330171doi: 10.1172/JCI111389google scholar: lookup
        57. Tanaka H, Kobayashi N, Maekawa T. Effect of thrombin and endotoxin on the in vivo metabolism of antithrombin III (AT III) in dogs.. Thromb Res 1985 Nov 1;40(3):291-306.
          pubmed: 4082111doi: 10.1016/0049-3848(85)90265-8google scholar: lookup

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