Abstract
Background: Lepirudin, a recombinant hirudin, is a direct acting thrombin inhibitor that has been used as a heparin alternative in patients with heparin-induced thrombocytopenia requiring on-pump cardiac surgery. To evaluate the efficacy, safety, and clinical utility of lepirudin as a cardiopulmonary bypass (CPB) anticoagulant, we compared lepirudin with heparin in a routine CPB setting. Methods: Twenty patients were randomly assigned to receive lepirudin (0.25 mg/kg b. w. bolus and 0.2 mg/kg b. w. added to the CPB priming) or heparin (400 U/kg b. w. bolus) with protamine reversal. Lepirudin and heparin anticoagulation during CPB was monitored using the ecarin clotting time or ACT, respectively and additional lepirudin (5 mg) or heparin (5000 U) boluses were administered. Results: The CPB circuit was performed in both groups without thromboembolic complications. Median blood loss during the first 36 hours was statistically higher (p = 0.007) in the lepirudin group (1.226 ± 316 ml) compared to the heparin group (869 ± 189 ml). One patient of the lepirudin group developed pulmonary embolism 24 hours after surgery. This patient was tested homozygous for the FV-Leiden mutation. Conclusion: Lepirudin provides effective CPB anticoagulation but induces a higher postoperative blood loss than heparin. Lepirudin should be restricted to patients undergoing CPB who cannot be exposed to heparin.
Key words
coronary bypass surgery - cardiopulmonary bypass - hirudin - heparin - anticoagulation
References
-
1
Edmunds Jr L H.
Blood-surface interactions during cardiopulmonary bypass.
J Cardiovasc Surg.
1993;
8
404-410
-
2
Slaughter T F, LeBleu T H, Douglas Jr J M. et al .
Characterization of prothrombin activation during cardiac surgery by hemostatic molecular markers.
Anesthesiology.
1994;
80
520-526
-
3
Bauer T L, Arepally G, Konkle B A. et al .
Prevalence of heparin-associated antibodies without thrombosis in patients undergoing cardiopulmonary bypass surgery.
Circul.
1997;
95
1242-1246
-
4
Warkentin T E, Greinacher A.
Heparin-induced thrombocytopenia and cardiac surgery.
Ann Thorac Surg.
2003;
76
638-648
-
5
Butterworth J, Lin Y A, Prielipp R C. et al .
Rapid disappearance of protamine in adults undergoing cardiac operation with cardiopulmonary bypass.
Ann Thorac Surg.
2002;
74
1589-1595
-
6 Poetzsch B, Madlener K. Management of cardiopulmonary bypass anticoagulation in patients with heparin-induced thrombocytopenia. Warkentin TE, Greinacher A Heparin-Induced Thrombcytopenia. New York, NY; Marcel Dekker 2004: 531-551
-
7 Greinacher A. Lepirudin for the treatment of heparin-induced thrombocytopenia. Warkentin TE, Greinacher A Heparin-Induced Thrombocytopenia. New York; Marcel Dekker 2004: 397-436
-
8
Walenga J M, Bakhos M, Messmore H L. et al .
Comparison of recombinant hirudin and heparin as an anticoagulant in a cardiopulmonary bypass model.
Blood Coagul Fibrinolysis.
1991;
2
105-111
-
9
Riess F C, Pötzsch B, Behr I. et al .
Recombinant hirudin as an anticoagulant during cardiac operations: experiments in a pig model.
Eur J Cardio-Thorac Surg.
1997;
11
739-745
-
10
Pötzsch B, Iversen S, Riess F C, Tzanova N, Seelig C, Nowak G, Müller-Berghaus G.
Recombinant hirudin as an anticoagulant in open-heart surgery: a case report [abstr].
Ann Hematol.
1993;
68 (Suppl 2)
A46
-
11
Riess F C, Löwer C, Seelig 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 Surg.
1995;
110
265-267
-
12
Riess F C, Pötzsch B, Bader R. et al .
A case report on the use of recombinant hirudin as an anticoagulant for cardiopulmonary bypass in open-heart surgery.
Eur J Cardio-Thorac Surg.
1996;
10
386-388
-
13 Riess F C, Poetzsch B, Mueller-Berghaus G. Recombinant hirudin as an anticoagulant during cardiac surgery. Pifarré R New Anticoagulants for the Cardiovascular Patient. Philadelphia; Hanley & Belfus 1997: 197-221
-
14
Koster A, Hansen R, Kuppe H. et al .
Recombinant hirudin as an alternative anticoagulant during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II: a 1-year experience in 57 patients.
Cardiothorac Vasc Anesth.
2000;
14
243-248
-
15
Koster A, Pasic M, Bauer M. et al .
Hirudin as anticoagulant for cardiopulmonary bypass: importance of preoperative renal function.
Ann Thorac Surg.
2000;
69
37-41
-
16
Longrois D, de Maistre E, Bischoff N, Dopff C, Meistelman C, Angioi M, Lecompte T.
Recombinant hirudin anticoagulation for aortic valve replacement in heparin-induced thrombocytopenia.
Can J Anaesth.
2000;
47
255-260
-
17
Pötzsch B, Madlener K, Seelig C. et al .
Monitoring of r-hirudin anticoagulation during cardiopulmonary bypass-assessment of the whole blood ecarin clotting time.
Thromb Haemost.
1997;
77
920-925
-
18
Chaitman B R, Alderman E L, Sheffield L T, Tong T, Fisher L, Mock M B, Weins R D, Kaiser G C, Roitman D, Berger R, Gersh B, Schaff H, Bourassa M G, Killip T.
Use of survival analysis to determine the clinical significance of new Q waves after coronary bypass surgery.
Circul.
1983;
67
302-311
-
19
Oberman A, Kouchoukos N T, Makar Y N, Russell Jr R O, Sheffield L T, Ray M, Allen R E, Kitts J R.
Perioperative myocardial infarction after coronary bypass surgery.
Cleve Clin Q.
1978;
45
172-81
-
20
Riess F C, Pötzsch B, Jäger K, Bleese N, Schaper W, Müller-Berghaus.
Elimination von rekombinantem Hirudin aus der Blutzirkulation mittels Hämofiltration. Untersuchungen im Schweinemodell.
Haemost.
1997;
17
200-204
-
21
Josa M, Siouffi S Y, Silvermann A B, Barsamian E M, Khuri S F, Sharma G V.
Pulmonary embolism after cardiac surgery.
J Am Coll Cardiol.
1993;
15
990-996
-
22
Rastan A J, Gummert J F, Lachmann N, Walther T, Schmitt D V, Falk V, Doll N, Caffier R, Richter M M, Wittekind C, Mohr F W.
Significant value of autopsy for quality management in cardiac surgery.
J Thorac Cardiovasc Surg.
2005;
129
1292-1300
MD Friedrich-Christian Riess
Albertinen Heart Center
Suentelstraße 11a
22457 Hamburg
Germany
Phone: + 49 40 55 88 24 45
Fax: + 49 40 55 88 24 21
Email: Friedrich-Christian.Riess@albertinen.de
