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Ann Thorac Surg 2000;69:37-41
© 2000 The Society of Thoracic Surgeons

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Original Articles

Hirudin as anticoagulant for cardiopulmonary bypass: importance of preoperative renal function

^a Deutsches Herzzentrum Berlin, Berlin, Germany

Address reprint requests to Dr Pasic, Deutsches Herzzentrum Berlin, Klinik für Herz-, Thorax- und Gefäßchirurgie, Augustenburger Platz 1, D-13353 Berlin, Germany
e-mail: pasic{at}dhzb.de

Presented at the Poster Session of the Thirty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 25–27, 1999.

	Abstract

Top Abstract Introduction Material and methods Results Comments References

 
Background. Recombinant hirudin is an alternative anticoagulant for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II. Although there is no neutralizing agent for recombinant hirudin, its fast renal elimination enables quick cessation of bleeding after cardiopulmonary bypass. The aim of the study was to compare anticoagulant effects of recombinant hirudin in regards to renal function in patients with heparin-induced thrombocytopenia type II.

Methods. Twenty-one patients (mean age, 65 years, and range, 35 to 82 years) underwent different complex cardiovascular procedures using recombinant hirudin as the anticoagulant for cardiopulmonary bypass. Postoperative blood loss, transfusion requirements, and hemostatic variables were compared between patients with a creatinine level lower than 1.5 mg/dL (group 1, normal renal function; n = 17 patients) and those with a creatinine level greater than 1.5 mg/dL (group 2, impaired renal function; n = 4 patients).

Results. The patients in group I showed no increased tendency toward postoperative bleeding. In contrast, all 4 patients in group 2 required reexploration for increased postoperative bleeding. They had higher activated partial thromboplastin times and transfusion requirements postoperatively.

Conclusions. If recombinant hirudin is used as the anticoagulant for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II and impaired renal function, the risk of postoperative bleeding is increased.

	Introduction

Top Abstract Introduction Material and methods Results Comments References

 
Heparin-induced thrombocytopenia is a possibly dangerous complication of therapy with heparin. The incidence after cardiac surgical procedures is low, about 1%, with a complication rate of approximately 50% and a mortality rate of 40% [1, 2]. There are two types of heparin-induced thrombocytopenia. Type I is characterized by the absence of thromboembolic complications and is rarely accompanied with a decrease in platelet count to less than 100,000/L. In contrast, in heparin-induced thrombocytopenia type II, the platelet count often rapidly decreases to values lower than 30,000/L and is often associated with thromboembolic complications. Its clinical manifestations include thrombosis and embolism of both the venous and arterial systems with stroke, pulmonary embolism, myocardial infarction, vascular occlusion, and venous thrombosis [2, 3]. Clinical criteria for the diagnosis are a decrease in platelet count, thromboembolic complications during the administration of heparin, or both. The diagnosis should be confirmed by laboratory assays: direct determination of the antibodies in the heparin–platelet factor 4 enzyme-linked immunosorbent assay or detection of heparin-induced platelet agglutination in the heparin-induced platelet aggregation assay. In patients who are exposed to heparin for the first time, heparin-induced thrombocytopenia type II usually develops after 7 to 14 days. After reexposure, it can recur within hours or immediately [4]. Therefore, if heparin-induced thrombocytopenia type II is clinically suspected and the diagnosis confirmed by laboratory assays, any heparin exposure should be stopped immediately, and alternative anticoagulation must be instituted [5]. Hirudin, a direct thrombin inhibitor that is clinically available as a recombinant preparation, has been used as an anticoagulant in patients with heparin-induced thrombocytopenia type II [5–7]. Its renal elimination occurs in approximately 60 minutes. However, there is no clinically applicable antidote, and therefore, the anticoagulant effects in patients with impaired renal function are unknown. The aim of this study was to compare anticoagulant effects of recombinant hirudin in regard to renal function in patients with heparin-induced thrombocytopenia type II.

	Material and methods

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Between June 1997 and June 1998, 21 patients (mean age, 65 years, and range, 35 to 82 years) with heparin-induced thrombocytopenia type II underwent different cardiovascular procedures using recombinant hirudin as the anticoagulant for cardiopulmonary bypass (CPB). There were 10 women and 11 men. Sixteen patients had a history of thromboembolic complications during previous exposure to either unfractionated heparin (14 patients) or low molecular weight heparin (2 patients). Repeat thromboembolic complications were seen in 10 patients and occurred as a single episode in 6. In 9 patients, the diagnosis was established before admission to our hospital, and in 12 patients, it was discovered during a routine preoperative study at our institution.

The patients were divided into two groups. Seventeen had a creatinine level lower than 1.5 mg/dL, and they were classified as group 1 (normal renal function). The other 4 patients had a creatinine level higher than 1.5 mg/dL and were regarded as group 2 (impaired renal function).

The mean left ventricular ejection fraction for the entire group of patients was 0.50 and ranged from 0.30 to 0.70. In 3 of the 4 patients with impaired renal function, the ejection fraction was significantly reduced (between 0.30 and 0.40), and in the other patient, it was normal. Ten patients were in New York Heart Association functional class III preoperatively, and 11 were in class IV, including all 4 patients with impaired renal function.

In all patients, anesthesia was accomplished by intravenous administration of propofol, sufentanil, and pancuronium bromide.

Myocardial revascularization was carried out in 11 patients, aortic valve replacement in 4, combined myocardial revascularization and mitral valve replacement in 3, myocardial revascularization combined with redo aortic valve replacement in 1 patient, and replacement of a descending thoracic aortic aneurysm in 2 patients. The cardiac procedures were done through a median sternotomy using standard CPB and moderate hypothermia of 32°C. Replacement of the descending thoracic aortic aneurysm was accomplished through a left posterolateral thoracotomy using femoral-femoral CPB and normothermia.

The CPB system consisted of a roller pump and a membrane oxygenator. The lines were primed with Ringer’s solution. For cardiac procedures, cardioplegic arrest was accomplished by infusion of crystalloid cardioplegic solution (Cardioplegin) into the aortic root or coronary ostia, followed by infusion of cold hydroxyethylene starch solution and topical cooling. Myocardial protection was maintained by repeated infusion of cold hydroxyethylene starch solution every 20 minutes thereafter.

Preoperative anticoagulation was achieved by continuous intravenous infusion of recombinant hirudin (Refludan; Hoechst, Frankfurt am Main, Germany) to obtain an activated partial thromboplastin time (aPTT) of 40 to 60 seconds. Perioperative anticoagulation was carried out according to the following protocol: Before arterial and venous cannulation, a bolus of recombinant hirudin (0.25 mg/kg of body weight) was given intravenously. Recombinant hirudin (0.2 mg/kg) was added to the priming solution of the CPB circuit. Cardiopulmonary bypass perfusion was started when the recombinant hirudin level reached a concentration between 3.5 and 4.0 µg/mL. The defined concentration of recombinant hirudin was maintained during CPB by continuous intravenous infusion. The monitoring of recombinant hirudin included the ecarin clotting time card for the TAS analyzer (Cardiovascular Diagnostics Inc, Raleigh, NC) and measurement of ecarin clotting time according to the original method [8], which uses the blank cartridges of the ACT II device (Medtronic, Parker, CO) (75-µL ecarin reagent, 150-µL sample). All measurements were performed in duplicate in citrated whole blood after 1:1 dilution with standard plasma to ensure adequate levels of prothrombin, which is necessary for reliable performance of the test [8].

Postoperatively, lower concentrations of recombinant hirudin were controlled by measurement of the aPTT in routine tests. Aprotinin (Antagosan; Hoechst) was given to all patients according to a high-dose regimen; an intravenous bolus of 2 x 10⁶ KIU for the patient, 2 x 10⁶ KIU for the priming solution of the CPB circuit, and a continuous infusion of 500,000 KIU/h during perfusion [9]. After cessation of CPB, blood from the heart-lung machine is successfully replaced with NaCl or RL solution. At the end the machine contains no blood, but only NaCl solution or RL. Further, forced diuresis was initiated with intravenous administration of 20 g of mannitol and, if necessary, repeated boli of 40 mg of furosemide. The immediate postoperative anticoagulation was accomplished with intravenous infusion of recombinant hirudin to achieve an aPTT of 40 to 60 seconds. It was changed 2 or 3 days thereafter to either coumarin or antiplatelet agents.

The indications for reexploration for bleeding were blood loss of more than 500 mL, 400 mL, or 300 mL during the first respective postoperative hours [(I) hour 500 ml; (II) hour > 400 ml; (III) hour > 300 ml] or total blood loss of more than 1,500 mL during the first 24 hours with an hourly portion of 100 mL or more. Transfusion of chest tube drainage blood was not performed.

Postoperative blood loss, transfusion requirements, and hemostatic variables were compared between group 1 (creatinine < 1.5 mg/dL, normal renal function) and group 2 (creatinine > 1.5 mg/dL, impaired renal function). Statistical analysis was performed with the Student t test. Statistical significance was defined as a probability value of 0.05 or less.

	Results

Top Abstract Introduction Material and methods Results Comments References

 
Heparin-induced thrombocytopenia type II was found in 21 patients, an incidence of 0.5% among all patients having a cardiovascular operation at our institution during the 1-year period. In 18 of these 21 patients, the diagnosis was based on the functional heparin-induced platelet aggregation assay (aggregation in three of four chambers minimum). Seven of the 21 patients demonstrated a cross-reactivity with the heparinoid danaparoid sodium (Orgaran) in the heparin-induced platelet aggregation assay. Direct proof of the heparin/platelet factor 4 antibody in the heparin–platelet factor 4 enzyme linked immunoabsorbent assay occurred in 17 patients (including 3 patients in whom the diagnosis of heparin-induced thrombocytopenia type II was made elsewhere and in whom only this assay was performed).

There were no significant differences in biometric data, duration of CPB, aortic cross-clamp time, recombinant hirudin requirement, and need of inotropic support between the two groups (Table 1). All CPB systems were examined for clot formation after operation. No such formations were found.

Prolongation of the aPTT for about 6 hours postoperatively was observed in all patients after CPB. This was a common finding after perfusion regardless of preoperative renal function. The aPTT values immediately after admission to the intensive care unit were higher in group 2 than in group 1. During the early postoperative period of 6 hours, the aPTT normalized in group 1 but remained prolonged (> 120 seconds) in group 2 (see Table 1).

Blood loss during the first 12 postoperative hours and transfusion requirements were significantly increased in group 2 (see Table 1). Eight patients in group 1 needed no transfusion of blood products either during or after operation. All patients in group 2 demonstrated a significantly increased requirement of transfusions (see Table 1), and ultimately all underwent reexploration because of an increased bleeding tendency. During reexploration, no surgical source was found as the cause of prolonged and increased postoperative hemorrhage.

The postoperative course of all patients in group 1 was uneventful. In group 2, 1 patient needed prolonged ventilatory support, and 2 patients died during the early postoperative period, 1 of acute myocardial failure and the other of septic multiorgan failure after acute aortic valve endocarditis.

	Comments

Top Abstract Introduction Material and methods Results Comments References

 
Our results show that preoperative renal function influences postoperative blood loss and transfusion requirements in patients with heparin-induced thrombocytopenia type II when recombinant hirudin is used as an alternative anticoagulant for CPB. The patients with preoperatively impaired renal function demonstrated an increased rate of reexploration for bleeding, independent of the duration of CPB.

Another important observation of our study was the prolongation of the aPTT for at least 6 hours after operation in all patients after CPB, regardless of preoperative renal function. In the patients with nonimpaired renal function, this prolongation in anticoagulation assays was not associated with an increased bleeding tendency, but in patients with impaired renal function, it was. Therefore, until an antidote for recombinant hirudin is clinically available or an effective method for its extracorporeal elimination is developed, the use of this medication in patients with already impaired renal function or patients with an increased risk for the development of postoperative renal failure should be critically evaluated. However, if renal failure develops in a patient with previously nonimpaired renal function, hemodiafiltration is the only option to date to augment recombinant hirudin elimination and should be initiated immediately.

Hirudin, available in Germany since 1997 as a recombinant preparation, is a peptide composed of 65 amino acids and is the most potent thrombin inhibitor known [10, 11]. The anticoagulant effect of recombinant hirudin is achieved by its binding to the core region of the thrombin molecule [6]. In contrast to unfractionated heparin, which inactivates only free plasma thrombin, recombinant hirudin also inactivates platelet and clot-bound thrombin [7] and thereby reveals enhanced thrombolysis [8]. Compared with other alternative anticoagulants, recombinant hirudin has several advantages: Its protein structure does not cross-react with heparin-induced antibodies; it provides immediate efficient anticoagulation, and because of the strong antithrombin effect, it inhibits a major sequence in the cascade of associated thromboembolism; and its blood levels can be closely monitored by measurements of the aPTT and the ecarin clotting time. The major disadvantage is that there is no antidote available for clinical use. Despite this management problem, its fast renal elimination in approximately 60 minutes allows no major coagulation problem after CPB in patients with good renal function.

Successful use of the combination of unfractionated heparin with prostaglandin has been reported [12]. However, even if the effectiveness of a certain concentration of the antiplatelet agent is documented by titration of the prostaglandin and inhibition of agglutination in the heparin-induced platelet aggregation assay, these in vitro results have to be evaluated critically for clinical use. Although the antiplatelet effect during heparinization can be monitored by platelet-function assays as the heparinase or protamine thromboelastogram, it remains doubtful that these results from in vitro studies can be transferred to an in vivo situation [13]. This is particularly true during the early period of perfusion during CPB when platelets are stimulated and platelet factor 4 is increasingly released. Moreover, less information is available concerning the biological half-life and elimination of the heparin/heparin-antibody complex. It remains uncertain whether protamine sulfate can bind to the heparin part and thereby possibly neutralize the immune complex. However, coagulation has to be reinstituted after cessation of CPB, and the antiplatelet effect must be reversed. Therefore, even in the case of a noncomplicated perfusion during CPB, circulating immune complexes can bind to functionally recovered platelets, thus leading to heparin-induced platelet aggregation after CPB.

The other possible alternative anticoagulants for CPB are ancrod and the heparinoid danaparoid sodium (Orgaran). The defibrinating agent ancrod has been successfully used for CPB in patients with heparin-induced thrombocytopenia type II [14]. As the fibrinogen stores have to be depleted, the anticoagulant effect is achieved approximately 12 hours after the initiation of therapy. Therefore, ancrod is not appropriate for emergency situations, including emergency CPB. Further, once the anticoagulant effect is reversed by infusion of fibrinogen-cryoprecipitate, CPB cannot be reinstituted immediately.

The heparinoid danaparoid sodium (Orgaran) is widely used as an alternative anticoagulant in patients with heparin-induced thrombocytopenia type II [15]. Similar to low molecular weight heparin, the anticoagulant effect is achieved through activity against the plasma coagulation factor Xa, which to date cannot be monitored online. Moreover, it remains unclear whether institution of anticoagulation only by inhibition of factor Xa activity is sufficient for CPB. Thrombosis of grafts after myocardial revascularization and repetitive clotting of the CPB system during perfusion with danaparoid sodium have been reported [16, 17]. Also, the anticoagulant effect cannot be reversed by protamine. This is of special importance for the reinstitution of hemostasis, as the biological elimination half-life of Orgaran approximates 7 to 15 hours. Severe bleeding complications after the use of Orgaran as anticoagulation for CPB can lead to multiple reexplorations [17]. Because of the heparin sulfate fraction in the preparation, immune cross-reaction with heparin-induced antibodies can occur in 7% to 10% of patients [3]. Therefore, before Orgaran is given to patients with heparin-induced thrombocytopenia type II, this cross-reaction has to be excluded by functional tests, thereby limiting its use in emergency situations.

This retrospective study included only a small number of patients who underwent different types of complex operations. Despite these important limitations, the results of the study indicate that recombinant hirudin is an option for anticoagulation during CPB in patients with heparin-induced thrombocytopenia type II and nonimpaired renal function. In these patients, application of recombinant hirudin does not lead to increased blood loss and transfusions. However, impairment of renal function includes an increased risk of bleeding.

	Acknowledgments

 
We are indebted to Mertzlufft Friedrich, MD, PhD, Homburg-Saar, Germany, for his constructive suggestions and to Ms Tonie Derwent for editorial assistance.

	References

Top Abstract Introduction Material and methods Results Comments References

 

1. Walls J.T., Curtis J.J., Silver D. Heparin-induced thrombocytopenia in patients who undergo open heart surgery. Surgery 1990;108:686-693.[Medline]
2. Slaughter T.F., Greenberg C.S. Heparin-associated thrombocytopenia and thrombosis—implications for perioperative management. Anesthesiology 1997;87:667-675.[Medline]
3. Vun C.M., Evans S., Chong B.H. Cross-reactivity study of low-molecular-weight heparins and heparinoid in heparin-induced thrombocytopenia. Thromb Res 1996;81:525-532.[Medline]
4. Nowack G., Bucha E., Brauns I., Czerwinski R. Anticoagulation with r-hirudin in regular haemodialysis with heparin-induced thrombocytopenia (HITII). The first long-term application of r-hirudin in a haemodialysis patient. Wien Klin Wochenschr 1997;109:354-358.[Medline]
5. Schiele F., Vuillemenot A., Kramarz P., et al. Use of recombinant hirudin as antithrombotic treatment in patients with heparin-induced thrombocytopenia. Am J Hematol 1995;50:20-25.[Medline]
6. Riess F.C., Pötzsch B., Bleese N., et al. Rekombinantes Hirudin als Antikoagulanz für den kardiopulmonalen Bypass in der Herzchirurgie. Z Herz-, Thorax-, Gefäßchirurgie 1997;11:79-87.
7. Koster A., Kuppe H., Hetzer R., Sodian R., Crystal G., Mertzlufft F. Emergent cardiopulmonary bypass in five patients with heparin-induced thrombocytopenia type II employing recombinant hirudin. Anesthesiology 1998;89:777-780.[Medline]
8. Pötzsch B., Madlener K., Seelig C., Riess C.F., Greinacher A., Müller-Berghaus G. Monitoring of r-hirudin anticoagulation during cardiopulmonary bypass—assessment of the whole blood ecarin clotting time. Thromb Haemost 1997;77:920-925.[Medline]
9. Dietrich W., Spannagl M., Jochum M., et al. Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization. Anesthesiology 1990;77:1119-1126.
10. Greinacher A., Völpel H., Jansens U., et al. Recombinant hirudin (lepirudin) provides safe and effective anticoagulation in patients with heparin-induced thrombocytopenia. Circulation 1999;99:73-80.[Abstract/Free Full Text]
11. Stephen J.G., Sanderson P.E.J. Novel anticoagulants based on direct inhibition of thrombin and factor Xa. Coronary Artery Dis 1998;9:75-81.[Medline]
12. Kraenzler E.J., Starr N.J., Miller M.L., Schiavone W.A. Heparin-associated thrombocytopenia. Anesthesiology 1988;69:964-967.[Medline]
13. Spiess B.D., Wall M.H., Gillies B.S., Fitch J.C., Soltow L.O., Chandler W.L. A comparison of thrombelastography with heparinase or protamine sulfate in vitro during heparinized cardiopulmonary bypass. Thromb Haemost 1997;78:820-826.[Medline]
14. O-Yurvati A.H., Laub G.W., Southgate T.J., McGrath L.B. Heparinless cardiopulmonary bypass with ancrod. Ann Thorac Surg 1994;57:1656-1658.[Abstract]
15. Doherty D.C., Ortel T.L., de Bruijn N., Greenberg C.S., Van Trigt P., III "Heparin-free" cardiopulmonary bypass. Anesthesiology 1990;73:562-565.[Medline]
16. Insler S.R., Kraenzler E.J., Bartholomew J.R., Kottke-Marchant K., Lytle B., Starr N.J. Thrombosis during the use of the heparinoid Organon 10172 in a patient with heparin-induced thrombocytopenia. Anesthesiology 1997;86:495-498.[Medline]
17. Westphal K., Martens S., Strouhal U., et al. Heparin-induced thrombocytopenia type II. Thorac Cardiovasc Surg 1997;45:318-320.[Medline]

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