Effects of Human Antithrombin III on Mortality and Blood Coagulation Induced in Rabbits by Endotoxin

Summary

Twenty-one rabbits were infused with 20μg/kg/hr of E. coli endotoxin for 6 hr. Eight of the animals were preinjected immediately before the infusion of endotoxin, with a bolus dose of human AT III calculated to increase the antithrombin content of the plasma by about 4 units/ml. All eight animals which were preinjected with AT III survived, while 5 of the 13 control rabbits infused with endotoxin alone died. The changes in coagulation parameters from the baseline values, between the 8 control rabbits which survived and the 8 animals which were preinjected with AT III were compared. The concentration of the preinjected human AT III declined significantly faster (P: <0.01) than that of the native rabbit AT III. AT III prevented the decline of F.XII throughout the infusion of the endotoxin. However, the decline in F.V, fibrinogen, prothrombin and platelets was not affected (P: >0.5) by the injection of AT III.

Keywords

Antithrombin III - Endotoxin - Intravascular coagulation

• References

• 1 Petersdorf RG. Septic shock. In: Harrison’s Principles of Internal Medicine. Petersdorf RG, Adams RD, Braunwald E, Isselbacher KJ, Martin JB, Wilson JD. (Eds) Me Graw Hill Book Co; New York: 1983
• 2 Morrison DC, Cochrane CG. Direct evidence for Hageman factor (factor XII) activation by bacterial lipopolysaccharides (endotoxins). J. Exper Med 1974; 140: 797-811
• 3 Rietschel ET, Schade U, Jensen M, Wollenweber HW, Luderitz O, Greisman SG. Bacterial endotoxins: Chemical structure, biological activity and role in septicemia. Scand J Infect Dis 1982; suppl (Suppl. 31) 8-21
• 4 Osterud B, Bjorklid E. Human factor VII associated with endotoxin stimulated monocytes in whole blood. Biochem Biophys Res Commun 1982; 108: 620-626
• 5 Colucci M, Balconi G, Lorenzet R, Pietra A, Donati MB, Semeraro N. Evidence that cultured human endothelial cells (EC) generate tissue factor in response to endotoxin. Thromb Haemostas 1983; 50: 253 (Abstr)
• 6 Damus PS, Hicks M, Rosenberg RD. Anticoagulant action of heparin. Nature 1973; 246: 355-357
• 7 Lahiri B, Rosenberg R, Talamo RC, Mitchell B, Bagdasarian A, Colman RW. Antithrombin III: An inhibitor of human plasma kallikrein. Fed Proc 1974; 33: 642
• 8 Rosenberg JS, McKenna PW, Rosenberg RD. Inhibition of human factor IXa by human antithrombin. J Biol Chem 1975; 250: 8883-8888
• 9 Seegers WH, Marciniak E. Inhibition of autoprothrombin C activity with plasma. Nature 1962; 193: 1188-1190
• 10 Highsmith RF, Rosenberg RD. The inhibition of human plasmin by human antithrombin-heparin cofactor. J Biol Chem 1974; 249: 4335-4338
• 11 Miller-Andersson M, Borg H, Andersson LO. Purification of antithrombin III by affinity chromatography. Thromb Res 1974; 5: 439-452
• 12 Wickerhauser M, Williams C. Isolation of antithrombin III without interfering with ethanol fractionation system. Thromb Haemostas 1979; 42: 168 (Abstr)
• 13 Holleman WH, Coen LJ, Capobianco JO, Barlow GH. Isolation of human antithrombin III by affinity chromatography on heparin- agarose. Thromb Haemostas 1977; 38: 201 (Abstr)
• 14 Ware AG, Seegers WH. The two stage procedure for the quantitative determination of prothrombin concentration. Am J Clin Path 1949; 19: 471-478
• 15 Blombäck B, Blombäck M. Purification of human and bovine fibrinogen. Arkiv Kemi 1956; 10: 415-413
• 16 Huseby RM, Bang NU. Fibrinogen. In: Thrombosis and Bleeding Disorders. Theory and Methods. Bang NU, Beller FK, Deutsch E, Mammen EF. (Eds) Academic Press; New York: 1971. pp 222-247
• 17 Odegard OR, Lie M, Abildgaard U. Heparin cofactor activity measured with an amidolytic method. Thromb Res 1975; 6: 287-294
• 18 Klein PD, Seegers WH. The nature of plasma antithrombin activity. Blood 1950; 5: 742-752
• 19 Lämmle B, Tran TH, Duckert F. Plasma prekallikrein (PPK), factor XII (F XII), antithrombin III (AT III) in intensive care patients with suspected disseminated intravascular coagulation. Thromb Haemostas 1983; 50: 290 (Abstr)
• 20 Griffin JH. The role of surface-dependent activation of Hageman factor (factor XII). Proc Nat Acad Sci 1978; 75: 1998-2002
• 21 Griffin JH, Cochrane CG. Recent advances in the understanding of contact activation reactions. Semin Thromb Hemost 1979; 5: 254-273
• 22 Wiggins RC, Cochrane CC. The autoactivation of rabbit Hageman factor. J Exp Med 1979; 150: 1122-1133
• 23 Saito H, Goldsmith G, Ratnoff OD. Fletcher factor activity in plasmas of various species. Proc Soc Exp Biol Med 1974; 147: 519-523
• 24 Alving BM, Tankersley DL, Mason BL. Plasma prekallikrein: Quantitative determination by direct activation with Hageman factor fragment (β-XIIa). J Lab Clin Med 1983; 101: 226-241
• 25 Triantaphyllopoulos DC. Antithrombin III (AT III) offers no advantage in treatment of tissue factor-induced intravascular coagulation. Fed Proc 1982; 41: 290
• 26 Mann LT, Simonsen M, Abildgaard U. Antithrombin III: Protection against death after injection of thromboplastin. Science 1969; 166: 517-518