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Influence of heparin dosage on hemostasis under combined use of nafamostat mesilate during deep hypothemic circulatory arrest

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Abstract

Objective: Nafamostat mesilate (NM) is a guanidine acid derivative which is synthesized in Japan as an antifibrinolytic drug. It has been successfully used to decrease blood loss and blood product requirement in cardiac operations. As there have been some reports that insufficient heparinization might induce the coagulopathic state in aprotinin-treated patients undergoing deep hypothermia and circulatory arrest (DHCA), we have reviewed 16 consecutive patients who underwent total aortic arch replacement using DHCA and the associated use of NM. Methods: The patients were divided into two groups; a Normaldosage Group(n=8) who received 3 mg/kg of heparin, and a Low-dosage Group (n=8) who received 1.5 mg/kg of heparin. The Celite-activating clotting time was maintained at longer than 1,000 seconds in both groups. Blood loss, transfusion requirements and the volume of postoperative mediastinal tube drainage were compared between the two groups. Results: We observed no adverse effects of NM and no significant difference in transfusion requirements between both groups. There was a significant diffierence in blood loss during the operation between the two groups (p<0.05) (Low-dosage Group 1,973±959 ml vs Normal-dosage Group 1,059±704ml). Conclusions: NM was a safe antifibrinolytic drug. Adequate heparinization was necessary to reduce hemorrhage in patients under going aortic arch replacement using DHCA and the associated use of NM.

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References

  1. Reed RL 2nd, Bracey AW Jr, Hudson, JD, Miller TA, Fischer, RP. Hypothermia and blood coagulation: Dissociation between enzyme activity and clotting factor levels, Circ Shock 1990;32: 141–52.

    PubMed  Google Scholar 

  2. Westaby S. Coagulation disturbances in profound hypothermia: The influence of anti-fibrinolytic therapy. Semin Thorac Cardiovasc Surg 1997; 9: 246–56.

    PubMed  CAS  Google Scholar 

  3. Fujii S, Hitomi Y. New synthetic inhibitors of C1r, C1, esterase, thrombin, plasmin, kallikrein and trypsin. Biochim Biophys Acta 1981; 661: 342–5.

    PubMed  CAS  Google Scholar 

  4. Miyamoto Y, Nakano S, Kaneko M, Takano H, Matsuda H. Clinical evaluation of a new synthetic protease inhibitor in open heart surgery: Effect on plasma serotonin and histamine release and blood conservation. ASAIO J 1992; 38: M395–8

    Article  PubMed  CAS  Google Scholar 

  5. Nakamura K, Yano M, Onituska T. Hypothermc cardiopulmonary bypass using Nafamostat Mesilate for reducing the hemorrhage in operations on the total aortic arch. Jpn J Artif Organs 2000; 29: 365–8.

    Google Scholar 

  6. Douglas AS, McNicol GP, Bain WH, Mackey WA. The haemostatic defect following extracorporeal circulation. Brit J Surg 1966; 53: 455–67.

    Article  PubMed  CAS  Google Scholar 

  7. Kongsgaard UE, Smith-Erichsen N, Geiran O, Amundsen E, Mollnes TE, Garred P, Different activation paterns in the plasma kallikrein-kinin and complement systems during coronary bypass surgery. Acta Anaesthesiol Scand 1989; 33: 343–7.

    Article  PubMed  CAS  Google Scholar 

  8. Campbell DJ, Dixson B, Kladis A, Kemme M, Santamaria JD. Activation of the kallikrein-kinin system by cardiopulmonary bypass in humans. Am J Physiol Regul Integr Comp Physiol 2001: 281: R1059–70.

    PubMed  CAS  Google Scholar 

  9. Stibbe J, Kluft C, Brommer EJP, Gomes M, de Jong DS, Nauta J. Enhanced fibrinolytic activity during cardiopulmonary bypass in open-heart surgery in man is caused by extrinsic (tissue-type) plasminogen activator. Eur J Clin Invest 1984; 14: 375–82.

    Article  PubMed  CAS  Google Scholar 

  10. Mojcik CF, Levy JH. Aprotinin and the systemic inflammatory response after cardiopulmonary bypass. Ann Thorac Surg 2001; 71: 745–54.

    Article  PubMed  CAS  Google Scholar 

  11. Dietrich W, Spath P, Ebell A, Richter JA. Prevalence of anaphylactic reactions to aprotinin: Analysis of two hundred forty-eight reexposures to aprotinin in heart operations. J Thorac Cardiovasc Surg 1997; 113: 194–201.

    Article  PubMed  CAS  Google Scholar 

  12. Sundt TM III, Kouchoukos NT, Saffitz JE, Murphy SF, Wareing TH, Stahl DJ, Renal dysfunction and intravascular coagulation with aprotinin and hypothermic circulatory arrest. Ann Thorac Surg 1993; 55: 1418–24.

    Article  PubMed  Google Scholar 

  13. Blauhut B, Gross C, Necek S, Doran JE, Spath P Lundsgaard-Hansen P. Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis, complement, and renal function after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1991; 101: 958–67.

    PubMed  CAS  Google Scholar 

  14. Westaby S, Forni A, Dunning J, Giannopoulos N, O’Regan D, Drossos G, et al. Aprotinin and bleeding in profoundly hypothemic perfusion. Eur J Cardiothorac Surg 1994; 8: 82–6.

    Article  PubMed  CAS  Google Scholar 

  15. Goldstein DJ, DeRosa CM, Mongero LB, Weinberg AD, Michler RE, Rose EA, et al. Safety and efficacy of aprotinin under conditions of deep hypothermia and circulatory arrest. J Thorac Cardiovasc Surg 1995; 110: 1615–21.

    Article  PubMed  CAS  Google Scholar 

  16. Rooney SJ, Bonser RS. The management of bleeding following surgery requiring hypothermic circulatory arrest. J Card Surg 1997: 12 (Suppl II): 238–42.

    PubMed  CAS  Google Scholar 

  17. Royston D. Serine protease inhibition prevents both cellular and humoral responses to cardiopulmonary bypass. J Cardiovasc Pharmacol 1996; 27 (Suppl I): S42–9.

    Article  PubMed  CAS  Google Scholar 

  18. Usui A, Hiroura M, Kawamura M, Hibi M, Yoshida K, Murakami F, et al. Nafamostat mesilate reduces blood-foreign surface reactions similar to biocompatible materials. Ann Thorc Surg 1996; 62: 1404–11.

    Article  CAS  Google Scholar 

  19. Sundaram S, Gikakis N, Hack CE, Niewiarowski S, Edmunds LH Jr, Rao, AK, et al. Nafamostat meislate, a broad spectrum protease inhibitor, modulates platelet, neutrophil and contact activation in simulated extracorporeal circulation. Thromb Heamost 1996; 75: 76–82.

    CAS  Google Scholar 

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Nakamura, K., Onitsuka, T., Yano, M. et al. Influence of heparin dosage on hemostasis under combined use of nafamostat mesilate during deep hypothemic circulatory arrest. Jpn J Thorac Caridovasc Surg 51, 186–191 (2003). https://doi.org/10.1007/s11748-003-0029-0

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  • DOI: https://doi.org/10.1007/s11748-003-0029-0

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