Heparin is still the major anticoagulant of choice during CPB, but it may cause thrombocytopenia and severe bleeding in patients. In light of these complications, the devel opment of new anticoagulant drugs seemed to be necessary for these patients. Many experimental studies focused on r-hirudin, which presented a less hemorrhagic effect than heparin. How ever, neither antagonist has been shown to reverse this effect.
Wachtfogel WT , Harpel PC, Edmunds LH Jr, Colman RWFormation of C 1s-C1-inhibitor, and plasmin-α2- plasmin inhibitor complexes during cardiopulmonary bypass. Blood1989;73:468.
2.
Brister SJ, Ofosu FA, Buchanan MRThrombin generation during cardiac surgery: heparin the ideal anticoagulant?Thromb Haemost1993;70:259.
3.
Baugh RF, Deemar KA, Zimmermann JJHeparinase in the activated clotting time assay: monitoring heparin—independent alterations in coagulation functions. Anesth Analg1992;74:201.
4.
Esposito RA, Culliford AJ, Colvin SBThe role of the activated clotting time in heparin administration and neutralization for cardiopulmonary bypass. J Thorac Cardiovasc Surg1983;85:174.
5.
Gravlee GP, Haddon SA, Rogers AT, et al. Heparin dosing and monitoring for cardiopulmonary bypass. J Thorac Cardiovasc Surg1990;99:518.
6.
Young JA, Kirker CT, Doty DBAdequate anticoagulation during cardiopulmonary bypass determined by activated clotting time and the appearance of fibrin monomer. Ann Thorac Surg1978;26:231.
7.
Chargaff E., Olson KBStudies on chemistry of blood coagulation VI. Studies on the action of heparin and other anticoagulants. The influence of protamine on the anticoagulant effect in vivo. J Biol Chem1937;122:153.
8.
Dietrich W., Spannagl M., Schramm W., et al. The influence of preoperative anticoagulation on heparin response during cardiopulmonary bypass. J Thorac Cardiovasc Surg1991;102:505.
9.
Havel M., Tenfelsbauer H., Knobl P.Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing CPB operation. J Thorac Cardiovasc Surg1991;101:968.
10.
Friesen RH, Clement AJIndividual responses to heparinization for extracorporeal circulation . J Thorac Cardiovasc Surg1979;72: 875.
Markwardt F.Development of hirudin as an antithrombotic agent. Semin Thromb Hemost1989;15:269.
13.
Markwardt F.Hirudin as an inhibitor of thrombin. Methods Enzymol1970;69:924.
14.
Doutremepuich C., Deharo E., Guyot M., et al. Antithrombotic activity of recombinant hirudin in the rat: A comparative study with heparin . Thromb Res1989;54:435.
15.
Harker L., Malpass TW, Branson HE, et al. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha granule release. Blood1980;56:824.
16.
Coleman RWPlatelet and neutrophil activation in cardiopulmonary bypass. Ann Thorac Surg1990;49:32.
17.
John Lch, Ress GM, Kovacs IBInhibition of platelet function by heparin: an etiological factor in post bypass hemorrhage. J Thorac Cardiovas Surg1993;105:816.
18.
Lindsay C., John H., Gareth M., Kovacs IBDifferent anticoagulants and platelet reactivity cardiac surgical patients . Ann Thorac Surg1993;56:899.
19.
Walenga J., Bakhos M., Messmore HL, et al. Potential use of recombinant hirudin as an anticoagulant in a cardiopulmonary bypass model. Ann Thorac Surg1991;51:271.
20.
Kaiser B., Markwardt F.Antithrombotic and hemorrhagic effects of synthetic and naturally occurring thrombin inhibitors. Thromb Res1986;43:613.
21.
Riess FC, Löwer C., Seclig C., et al. Recombinant hirudin as a new anticoagulant during cardiac operations instead of heparin: successful for aortic valve replacement in man. J Thorac Cardiovasc Surg1995;110:265.
22.
Nowak G., Bucha E.A new method for the therapeutical monitoring for hirudin. Thromb Haemost1993;69:27.
23.
Henny Ch P. , Ten Cate H., Ten Cate JWA randomized blind study comparing standard heparin and a new low-molecular weight heparinoid in cardiopulmonary bypass surgery in dogs. J Clin Lab Med1985;106:187.
24.
Massonnet-Castel S., Pelissier E., Dreyfus G., et al. Low-molecular weight heparin in extracorporeal circulation. Lancet1984;I:1182.
25.
Murray WGA preliminary study of low-molecular weight heparin in aortocoronary bypass surgery. In: Murray WG, ed. LMWH in surgical practice (Master of Surgery Thesis)London : University of London, 1985 :266.
Ockelford PA , Carter CJ, Cerskus A., et al. Comparison of the in vivo haemorrhagic and antithrombotic effects of a low antithrombin III affinity heparin fraction . Thromb Res1982;27:679.
28.
Cade JF, Buchanan HR, Boneu B.A comparison of the antithrombotic and hemorrhagic effects of low-molecular weight heparin fractions: the influence of the method of preparation. Thromb Res1984;35:613.
29.
Arthur UK, Isbister JP, Aspery EMThe heparin induced thrombosis-thrombocytopenia syndrome (HITTS): a review . Pathology1985;16:82.
30.
Hirsh J.Heparin induced bleeding. Nouv Rev Franc Hematol1984; 26:261.
31.
Azougagh Oualane F, Toulemonde F., Doutremepuich F., Doutremepuich C.Effects of aprotinin on heparin activities and neutralization with protamine. Thromb Res1993;68:185.
32.
Ross RL, Whittlesey GC, Splittgerber FH, et al. Rapid assays for heparin during extracorporeal circulation. Trans Am Soc Artif Inter Organs1986;13:274.
33.
Doutremepuich C., Gestreau H., Maury MO, et al. Experimental venous thrombosis in rats treated with heparin and a low molecular weight heparin fraction. Haemostasis1983;13:109.
34.
Kelton JG, Hirsh J.Bleeding associated with antithrombotic therapy. Semin Hematol1980;17:259.
35.
Reyers I., Mussoni L., Donati MB, de Gaetano G.Thrombosis induced by ligature of inferior vena cava (rats). Thomb Res1980; 18:669.
36.
Aguejouf O. , Doutremepuich F., Azougagh Oualane F, Doutremepuich C.Thrombogenicity of ionic and non ionic contrast media tested in a laser induced rat thrombosis model . Thromb Res1995;77:259.
37.
Belougne E. , Aguejouf O., Imbault P., et al. Experimental thrombosis model induced by laser beam. Application of aspirin and an extract of Ginkgo Biloba: Egb 761. Thromb Res1996 ;82:453.
38.
Aronson M., Fabian I., Bleiberg I.Mechanism of heparin rebound and heparin-protamine interactions. In: de Whited I, ed. Heparin new biochemical and medical aspects. Berlin: DeGruyter , 1983:69.
39.
Doutremepuich C., Bonini F., de Seze O., et al. Neutralisation d'une fraction d'héparine de très faible masse moléculaire CY222 par la protamine . Etude in vitro et in vivo. Thérapie1986 ;41:433.
40.
Doutremepuich C., Bonini F., Toulemonde F., et al. In vivo neutralization of low molecular weight heparin fraction CY216 by protamine. Semin Thromb Hemost1985;11:316.
41.
Racanelli A. , Hoppensteadt DA, Fareed J.In vitro protamine neutralization profiles of heparins differing in source and molecular weight . Semin Thromb Hemost1989;15:386.
42.
Racanelli A. , Fareed J., Walenga J., Coyne E.Biochemical and pharmacologic studies on the protamine interaction with heparin, its fractions and fragments. Semin Thromb Hemost1985; 11:176.
43.
Ando T., Yamasaki M., Suzuki K.Protamine: Isolation, Characterization Structure and Functions. New York: Springer Verlag, 1973:3.
44.
Kitani T., Nagarajan SC, Shanberge JNEffect of protamine on heparin ATIII complexes. In vitro studies. Thromb Res1980;17: 367.
45.
Kitani T., Nagarajan SC, Shanberge JNEffect of protamine on heparin ATIII complexes. In vivo studies. Thromb Res1980;17: 375.
46.
Massonnet-Castel S., Pelissier E., Bara L., et al. Partial reversal of low molecular weight Heparin (PK 10169) anti-Xa activity by protamine sulfate. In vitro and in vivo study during cardiac surgery with extracorporeal circulation . Haemostasis1986;16:139.
47.
Thomas DP, Barrowcliffe TW, Merton RE, et al. In vivo release of anti Xa clotting activity by a heparin analogue . Thromb Res1980; 17:831.
48.
Barrowcliffe TW, Merton RE, Gray E., Thomas DPHeparin and bleeding: an association with lipase release. Thromb Haemost1988;60:434.
49.
Diness V., Ostergaard PBNeutralization of LMWH (LHN-1) and conventional by heparin sulfates in rats . Thromb Haemost1986; 56:318.
50.
Bianchini P. , Osima B., Nader HB, Dietrich CPLack of correlation between in vitro and in vivo antithrombotic activity of heparin fractions and related compounds. Thromb Res1985;40:597.
