The effect of calcium administration on the blood coagulationmechanism during heparin infusion

헤파린 투여 중 칼슘 투여가 혈액응고 기전에 미치는 영향

  • 김일룡 (제주대학교 농과대학 수의학과) ;
  • 김근형 (싱가포르대학) ;
  • 김병선 (한국마사회) ;
  • 윤영민 (제주대학교 농과대학 수의학과) ;
  • 이경갑 (제주대학교 농과대학 수의학과)
  • Accepted : 2004.05.30
  • Published : 2004.09.30

Abstract

This study was performed to investigate the effects of calcium administration on the blood coagulation mechanism through APTT in the calf. Five male calves (70~90 kg) were used in this experiment. In the control group, heparinized normal saline (1 IU/kg/min) had been infusing into the jugular vein for 100 minutes. For the analysis of calcium effects on the APTT, the same solutions had been infusing during the first 40 minutes, subsequently the solution including calcium gluconate (3.3 mg/ml/min) had been infusing for 60 minutes. Blood samples were serially collected every 10 minutes for the APTT and platelets count and every 20 minutes for the calicum level during the infusion. In the calcium-treated group, after 70 minutes the APTT ratio (APTT heparin/APTT baseline) was higher than the therapeutic range. APTT was significantly increased at 50, 60 and 70 minutes in the calcium-treated group as compared to the control group (p<0.01). In the control group, calcium level was decreased significantly after heparin infusion (p<0.01). The platelet count was gradually decreased without significant variation in the both control and calcium-treated groups. These results suggested that APTT is slightly increased in combined heparin and calcium administration.

Keywords

References

  1. Abbott, T. R. Changes in serum calcium fractions and citrate concentrations during massive blood transfusions and cardiopulmonary bypass. Br. J. Anaesth. 1983, 55, 753-760
  2. Bain, B., Forster, T. and Sleigh, B. Heparin and activated partial thromboplastin time - A difference between the in-vitro and in-vivo effects and implicationsfor therapeutic range. Am. J. Clin. Pathol. 1980, 74, 668-673
  3. Beguin, S., Lindhout, T. and Hemker, H. C. The mode of action of heparin in plasma. Thromb. Haemost. 1988, 60, 457-462
  4. Capen, C. C. and Rosol, T. J. Calcium-regulating hormones and diseases of abnormal mineral. In Kaneko, J.J., ed., Clinical biochemistry of domestic animals, 4th ed., Academic press. p. 679, 1989
  5. Carlstedt, F., Lind, L., Joachimsson, P. O., Rastad, J., Wide, L. and Ljunghall, S. Circulating ionized calcium and parathyroid hormone levels following coronary artery by-pass surgery. Scand. J. Clin. Lab. Invest. 1999, 59, 47-53
  6. Carter, B. L. Therapy of acute thromboembolism with heparin and warfarin. Clin. Pharm. 1991, 10, 503-518
  7. Carter, B. L., Jones, M. E. and Waickman, L. A. Pathophysiology and treatment of deep-vein thrombosis and pulmonary embolism. Clin. Pharm. 1985, 4, 279-296
  8. Catinella, F. P., Cunningham, J. N. Jr., Strauss, E. D., Adams, P. X., Laschinger, J. C. and Spencer, F. C. Variations in total and ionized calcium during cardiac surgery. J. Cardiovasc. Surg. 1983, 24, 593-602
  9. Dodds, W. J. Hemostasis. In Kaneko, J.J., Clinical biochemistry of domestic animals, 4th ed., Academic press. pp. 274-315, 1989
  10. Fettman, M. J. Nutritional pharmacology. In Adams, H. R. Veterinary pharmacology and therapeutics. p. 724, 8th ed. Iowa state university press. 2001
  11. Greenberg, C. S., Adams, J. P., Mullen, P. E. and Koepke, J. A. The effect of calcium ions on the activated partial thromboplastin time of heparinized plasma. Am. J. Clin. Pathol. 1986, 86, 484-489
  12. Heras, M., Chesebro, J. H., Penny, W. J., Bailey, K. R., Lam, J. Y. T., Holmes, D. R., Reeder, G. S., Badimon, L. and Fuster, V. Importance of adequateheparin dosage in arterial angioplasty in a porcine model. Circulation 1988, 78, 654-660
  13. Hinkle, J. E. and Cooperman, L. H. Serum ionized calcium changes following citrated blood trasnfusion in anaesthetized man. Brit. J. Anaesth. 1971, 43, 1108-1112
  14. Hirsh, J. Drug therapy-heparin. N. Engl. J. Med. 1991, 324, 1565-1574
  15. Hirsh, J. and Fuster, V. Guide to anticoagulant therapy. Part 1: heparin. Circulation 1994, 89, 1449-1468
  16. Hirsh, J., Warkentin, T. E., Raschke, R., Granger, C., Ohman, E. M. and Dalen, J. E. Heparin and lowmolecular-weight heparin. Chest. 1998, 114, 489S-510S
  17. Holmes, D. R. Jr., Vlietstra, R. E., Reiter, S. J. and Bresnahan, D. R. Advances in interventional cardiology. Mayo. Clin. Proc. 1990, 65, 565-583
  18. King, D. J. and Kelton, J. G. Heparin-associated thrombocytopenia. Ann. intern. Med. 1984, 100, 535-540
  19. Landefeld, C. S., Cook, E. F., Flatley, M., Weisberg, M. and Goldman, L. Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy. Am. J. Med. 1987, 82, 703-713
  20. Ofosu, F. A., Hirsh, J., Esmon, C. T., Modi, G. J., Smith, L. M., Anvari, N., Buchanan, M. R., Fenton, J. W. and Blajchman, M. A. Unfractionated heparininhibits thrombin-catalyzed amplification reactions of coagulation more efficiently than those catalyzed by factor Xa. Biochem. J. 1989, 257, 143-150
  21. O’Reilly, R. A. Drugs used in disorders of coagulation. In Katzung, B. G., ed., Basic and clinical pharmacology. pp. 406-407, 4th ed., Appleton & lange, 1989
  22. Salzman, E. W., Rosenberg, R. D., Smith, M. H., Lindon, J. N. and Favreau, L. Effect of hepairn and hepairn fractions on platelet aggregation. J. Clin. Invest.1980, 65, 64-73
  23. Schiele, F., Vuillemenot, A., Kramarz, P., Kieffer, Y., Anguenot, T., Bernard, Y. and Bassand, J. P. Use of recombinant hirudin as antithrombotic treatment inpatients with heparin-induced thrombocytopenia. Am. J. Hematol. 1995, 50, 20-25
  24. Simko, R. J., Tsung, F. F. W. and Stanek, E. J. Activated clotting time versus activated partial thromboplastin time for therapeutic monitoring of heparin. Ann. Pharmacother. 1995, 29, 1015-1021
  25. Takkunen, O. Effects of heparin on serum ionized calcium and haemodynamics during coronary artery surgery. Acta. Anaesthesiol. Scand. 1989, 33, 75-78
  26. Teoh, K. H. T., Young, E., Bradley, C. A. and Hirsh, J. Heparin binding proteins-contribution to heparin rebound after cardiopulmonary bypass. Circulation 1993, 88, 420-425
  27. Triplett, D. A, Harms, C. S. and Koepke, J. A. The effect of heparin on the activated partial thromboplastin time. Am. J. Clin. Pathol. 1978, 70, 556-559
  28. Urban, P., Scheidegger, D., Buchmann, B. and Skarvan, K. The hemodynamic effects of heparin and their relation to ionized calcium levels. J. Thorac. Cardiovasc. Surg. 1986, 91, 303-306
  29. Warkentin, T. E. and Kelton, J. G. Heparin-induced thrombocytopenia. Annu. Rev. Med. 1989, 40, 31-44
  30. Westhorpe, R. N., Varghese, Z., Petrie, A., Wills, M. R. and Lumley, J. Changes in ionized calcium and other plasma constituents associated with cardiopulmonary bypass. Br. J. Anaesth. 1978, 50, 951-957
  31. Zucker, S. and Cathey, M. H. Control of heparin therapy. Sensitivity of the activated partial thromboplastin time for monitoring the antithrombotic effects ofheparin. J. Lab. & Clin. Med. 1969, 73, 320-326