Hikmet KOÇAK, Yahya ÜNLÜ, Salim B. TEKİN

Kardiyopulmoner Bypass Esnasında Protein-C ve Protein-S, Doku Plazminojen Aktivatörü ve Fibrinojen Düzeyleri

Amaç: Kardiyopulmoner bypass (KPB) esnas›nda kan›n yabanc› yüzeylerle temas›, koagulasyon sisteminin aktive olmas›na yol açar. Bu çal›flman›n amac› KPB öncesinde, esnas›nda ve sonras›nda protein C (PC) ve protein S (PS), doku plazminojen aktivatörü (t-PA) ve fibrinojen (F) düzeylerini de¤erlendirmektir. Yöntem ve gereç: Bu çal›flmaya elektif koroner arter bypass cerrahisi (KABC) yap›lan 33 hasta ve kardiyak cerrahi yap›lmayan 11 hasta (kontrol grubu) al›nd›. Kan örnekleri ameliyat öncesi, KPB öncesi, esnas› ve sonras›nda ve ameliyat sonras› olmak üzere farkl› zamanlarda al›nd›. KPB öncesinde, esnas›nda ve sonras›nda PC ve PS, t-PA ve F düzeyleri ölçüldü. Bulgular: KPB esnas›nda PC ve PS ve F düzeyleri azald› (p < 0.05). Bir hiperfibrinolizis markeri olan t-PA düzeyleri, KPB esnas›nda daha yüksekti. Bu durum KABC ile birlikte subklinik hemostatik aktivasyonun geliflti¤ini gösterebilir. KPB bafllang›c›nda aorttaki kros klemp kald›r›lmadan önce t-PA düzeyi 8 kat artt›, KPB esnas›nda ve ameliyat sonras› erken dönemde ise yüksek kald›. KPB süresince PC ve PS ve F düzeyleri azald› ve bu düflüfl KPB’›n sonuna kadar devam etti. Kontrol grubunda hemostatik markerler aras›nda anlaml› bir fark yoktu. Tüm parametreler için gruplar aras›nda anestezi indüksiyonundan önce ve KPB esnas›nda istatistiki olarak önemli fark vard› (p< 0.01). Sonuç: Bir hiperfibrinolizis markeri olan t-PA düzeyleri, KPB esnas›nda yüksekti ve ameliyat sonras› erken dönemde de yüksek kald›. Protein C ve PS ve F düzeyleri KPB süresince azald›. Bu sonuçlar trombin generasyonunun KPB esnas›nda artt›¤›n› göstermektedir.

Anahtar Kelimeler:

Kardiyopulmoner bypass, Protein C ve protein S sistemleri, Doku plazminojen aktivatörü, fibrinojen

Levels of Protein C and Protein S, Tissue-Plasminogen Activator, and Fibrinogen During Cardiopulmonary Bypass

Aim: The exposure of blood to foreign surfaces during cardiopulmonary bypass (CPB) leads to an activation of the coagulation system. The goal of this study was to evaluate the levels of protein C and protein S, tissue-plasminogen activator (t-PA) and fibrinogen before, during and after CPB. Materials and Methods: Thirty-three patients undergoing elective coronary artery bypass grafting (CABG) and 11 patients undergoing non-cardiac surgery (control group) were included in this study. Blood samples were taken at different time intervals preoperatively, before, during and after CPB, and in the postoperative period. Protein C and protein S, t-PA and fibrinogen levels were measured before, during and after CPB. Results: Protein C, protein S and fibrinogen levels were decreased during CPB (p

Keywords:

Cardiopulmonary bypass, protein C and protein S systems, tissue plasminogen activator, fibrinogen,

PDF

___

1. Linden MD. The hemostatic defect of cardiopulmonary bypass. J Thromb Thrombolysis 2003; 16(3): 129-47.
2. Teufelsbauer H, Proidl S, Havel M, Vukovich T. Early activation of hemostasis during cardiopulmonary bypass: evidence for thrombin mediated hyperfibrinolysis. Thromb Haemost 1992; 68(3): 250-2.
3. Petaja J, Peltola K, Sairanen H, Leijala M, Kekomaki R, Vahtera E et al. Fibrinolysis, antithrombin III, and protein C in neonates during cardiac operations. J Thorac Cardiovasc Surg 1996; 112: 665-71.
4. Despotis GJ, Avidan MS, Hogue CWJ. Mechanisms and attenuation of hemostatic activation during extracorporeal circulation. Ann Thorac Surg 2001; 72: S1821-31.
5. Knöbl PN, Zilla P, Fasol R, Muller MM, Vukovich TC. The proteinC system in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1987; 94: 600-5.
6. Gram J, Janetzko T, Jesperson J, Bruhn HD. Enhanced effective fibrinolysis following the neutralization of heparin in open-heart surgery increases the risk of post-surgical bleeding. Thromb Haemostas 1990; 63: 241-5.
7. Unlü Y, Atefl A, Tekin SB, Ceviz M, Becit N, Kuflkay S et al. The effects of extracorporeal circulation and various priming solutions on hemostasis. Turk J Thorac Cardiovasc Surg 1998; 6: 310-7.
8. Brister SJ, Ofosu FA, Buchanan MR. Is heparin the ideal anticoagulant? Thromb Haemost 1993; 70: 259-62.
9. Welters I, Menges T, Ballesteros M, Knothe C, Ruwoldt R, Görlach G et al. Thrombin generation and activation of the thrombomodulin protein C system in open heart surgery depend on the underlying cardiac disease. Thromb Res 1998; 92: 1-9.
10. Valen G, Eriksson E, Risberg B, Vaage J. Fibrinolysis during cardiac surgery. Release of t-PA activator in arterial and coronary sinus blood. Eur J Cardiothorac Surg 1994; 8: 324-30.
11. Chandler WL, Fitch JCK, Wall MH, Verrier ED, Cochran RP, Soltow LO et al. Individual variations in the fibrinolytic response during and after CPB. Thromb Haemost 1995; 74: 1293-7.
12. Gram J, Janetzko T, Jespersen J, Bruhn H. Enhanced effective fibrinolysis following the neutralization of heparin in open heart surgery increases the risk of post-surgical bleeding. Thromb Haemost 1990; 63: 241-5.
13. Ray MJ, Marsh NA, Hawson GAT. Relationship of fibrinolysis and platelet function to bleeding after CPB. Blood Coagul Fibrinolysis 1994; 5: 679-85.
14. Chandler WL, Velan T. Secretion of t-PA and plasminogen activator inhibitor 1 during CPB. Thromb Res 2003; 112: 185- 92.
15. Speekenbrink RGH, Bertina RM, Espana F, Wildevuur CRH, Eijsman L. Activation of the protein C system during CPB with and without aprotinin. Ann Thorac Surg 1998; 66: 1998-2002.
16. Clouse LH, Comp PC. The regulation of hemostasis: the protein C system. N Engl J Med 1986; 314: 1298-304.
17. Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Imeson JD, Mellows S et al. Hemostatic function and ischemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 2: 533-7.
18. Maruyama I. Thrombomodulin, an endothelial anticoagulant; its structure, function and expression. Jpn Circ J 1992; 56: 187-91.
19. Y›lmaz M, Haznedaro¤lu IC, Kirazl› fi, Paflao¤lu I. Effects of extracorporeal circulation on thrombin-antithrombin III and prothrombin fragment 1+2 levels. Clin Appl Thromb Hemost 2002; 8(1): 61-3.
20. Casati V, Gerli C, Franco A, Della Valle P, Benussi S, Alfieri O et al. Activation of coagulation and fibrinolysis during coronary surgery: on-pump versus off-pump techniques. Anesthesiology 2001; 95: 1103-9.
21. Boldt J, Schindler E, Knothe CH, Hammermann H, Daffer F, Hempelmann G. Endothelial-related coagulation in cardiac surgery. Br J Anaesth 1995; 74: 174-9.
22. Bithell TC. Blood coagulation. In: Cann CC, editor. Wintrobe’s Clinical Hematology. Malvern, Pennsylvania: Lea and Febiger; 1993. pp. 566-615.
23. Manucci PM, Vigonos S. Deficiencies of protein-C, an inhibitor of blood coagulation. Lancet 1982; 2: 463-7.
24. Lu H, Du Buit C, Soria J, Touchot B, Chollet B, Commin PL et al. Postoperative hemostasis and fibrinolysis in patients undergoing cardiopulmonary bypass with or without aprotinin therapy. Thromb Haemost 1994; 72(3): 438-43.
25. Wall U, Jern S, Tengborn L, Jern C. Evidence of a local mechanism for desmopressin-induced t-PA release in human forearm. Blood 1998; 91: 529-37.
26. Wada H, Ohiwa M, Kaneko T, Tamaki S, Tanigawa M, Shirakawa S et al. Plasma thrombomodulin as a marker of vascular disorders in thrombotic thrombocytopenic purpura and disseminated intravascular coagulation. Am J Hemato