Is Heparin the Ideal Anticoagulant for Cardiopulmonary Bypass? Dermatan Sulphate May Be an Alternate Choice

Summary

Performance of cardiopulmonary bypass (CPB) during cardiac surgery requires the administration of high dose heparin to prevent CPB pump occlusion. However, this heparin use is associated with bleeding side-effects. Moreover, at the end of CPB, the heparin must be neutralized with protamine sulphate, which is also associated with adverse side-effects. A number of recent studies suggest that dermatan sulphate may be useful as an alternate anticoagulant to heparin. We determined whether CPB could be performed using dermatan sulphate instead of heparin, in an adult pig CPB model. When heparin was used, a high dose (> 200 U/kg, which generated > 3 anti-thrombin U/ml of plasma), was required to perform successful CPB and to maintain CPB pump patency. This dose was associated with a post CPB bleeding of ≈ 600 ml/2h. in contrast, successful CPB could be achieved when the pigs were given lower doses of dermatan sulphate than heparin, which in turn, were associated with less bleeding. We conclude that dermatan sulphate may be an alternate anticoagulant for cardiac surgery

• References

• 1 Marengo-Rowe AJ, Leveson JE. Fibrinolysis: A Frequent Cause of Bleeding. In: Effective Hemostasis in Cardiac Surgery. A Society of Cardiovascular Anesthesiololgists Monograph Ellison D, Jobes DR. (eds) W. B. Saunders Co. Philadelphia; 1988: 41-55
• 2 Woodman RC, Harker LA. Bleeding complications associated with cardiopulmonary' bypass. Blood 1990; 76: 1680-97
• 3 Teoh K, Young E, Bradley CA, Hirsh J. Heparin binding proteins: Contribution to heparin rebound following cardiopulmonary bypass. Circ. 1933. in Press.
• 4 Warkentin TE, Kelton JG. Heparin and Platelets In: Platelets in Health and Disease. Hematology/Oncology Clinics of North America 1990; 4 (01) 243-64
• 5 Umlas J, Taff RH, Garvin G, Sevierk P. Anticoagulant monitoring and neutralization during open heart surgery - a rapid method for measuring heparin and calculating safe reduced protamine doses. Analg 1983; 62: 1095-9
• 6 Cole CW, Bormanis J. Ancrod: A practical alternative to heparin. J Vase Surg 1988; 8: 59-63
• 7 Kappa JR, Horn MKIII, Fisher CA, Ellison N, Addonizio Jr VP. Efficacy of iloprost (ZK36374) versus aspirin in preventing heparin-induced platelet activation during cardiac operations. J Thorac Cardiovasc Surg 1987; 94: 405-13
• 8 Walenga JM, Bakhos M, Messmore HL, Fareed J, Pifarre R. Potential use of recombinant hirudin as an anticoagulant in cardiopulmonary bypass model. Ann Thorac Surg 1991; 51: 271-7
• 9 Hogg DJ, Jackson CM. Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: Implications for heparin efficacy. Proc Natl Acad Sci 1989; 86: 619-23
• 10 Bar-Shavit R, Eldor A, Vlodavsky I. Binding of thrombin to subendothelial extracellular matrix. J Clin Invest 1989; 84: 1096-104
• 11 Okwusidi JI, Falcone M, Van-Ryn-McKenna J, Hirsh J, Ofosu FA, Buchanan MR. In vivo catalysis of thrombin inhibition by antithrombin III or heparin co-factor II and antithrombotic effect: differential effects of unfractionated heparin and dermatan sulfate. Thromb Haemorrh Disorders 1990; 1: 77-80
• 12 Okwusidi JI, Anvari N, Kulczycky M, Blajchman MA, Buchanan MR, Ofosu FA. Fibrin moderates the catalytic action of heparin but not that of dermatan sulfate on thrombin inhibition in human plasma. J Lab Clin Med 1991; 117: 359-64
• 13 Bendayan P, Boneu B, Boccalon P. Dermatan sulfate is a more potent inhibitor of clot-bound thrombin than unfractionated and low molecular weight heparins. Thromb Haemostas 1993; 69: 656
• 14 Murata K. Distribution of acidic glycosaminoglycans; lipids and water in normal human cerebral arteries of various ages. Stroke 1985; 16: 685-7
• 15 Fernandez F, Van Ryn J, Ofosu FA, Hirsh J, Buchanan MR. The hemorrhagic and antithrombotic effects of dermatan sulphate. Brit J Haematol 1986; 64: 309-17
• 16 Ryan KE, Lane DA, Flynn A, Ireland H, Boisclair M, Sheppard J, Curtis JR. Antithrombotic properties of dermatan sulfate (MF701) in haemodialysis for chronic renal failure. Thromb Haemostas 1992; 68: 563-9
• 17 Nurmohamed MT, Knipscheer HC, Stevens P, Krediet PT, Roggekamp MC, Berckmans RJ, TenCate JW. Clinical experience with a new anticoagulant (dermatan sulfate) in chronic hemodialysis patients. Clin Nephrol 1993; 39: 166-71
• 18 Agnelli G, Cosmi B, De Fillipo P, Ranucci V, Veschi F, Longetti M, Renga C, Barzi F, Gianese F, Lupattelli L, Rinonapoli E, Nenci GG. A randomized double-blind, placebo-controlled trial of dermatan sulfate for prevention of deep vein thrombosis in hip fracture. Thromb Haemostas 1992; 67: 203-8
• 19 Prandoni P, Meduri F, Cuppini S, Toniato A, Zangrandi F, Polistena P, Gianese F, Maffei-Faccioli A. Dermatan sulfate: A safe approach to prevention of postoperative deep vein thrombosis. Br J Surg 1992; 79: 505-9
• 20 Cohen AT, Phillips MJ, Edmondson RA, Melissari E, Vaidynathan I, Kakkar VV. Dermatan sulphate for prophylaxis of deep vein thrombosis (DVT) in elective hip surgery: a dose finding trial. Thromb Haemostas 1993; 69: 621
• 21 Larsen ML, Abildgaard U, Teien AN, Gjesdal K. Assay of plasma heparin using thrombin and the chromogenic substrate H-D-phe-pip-arg-p-NA (S-2238). Thromb Res 1978; 13: 285-8
• 22 CCAC - Guide to the Care and Use of experimental animals. Canada Council of Animal Care Vol. (; 2). 1984
• 23 Minitab, Reference Manual. Minitabs Inc. State College. PA. 1988
• 24 Hull R, Hirsh J. Advances and controversies in the diagnosis prevention and treatment of venous thromboembolism. Prog Hematol 1984; 12: 73-123