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Ann Thorac Surg 2001;71:1041-1042
© 2001 The Society of Thoracic Surgeons

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Case report

Emergency cardiopulmonary bypass in a bilaterally nephrectomized patient with a history of heparin-induced thrombocytopenia: successful reexposure to heparin

^a Departments of Anesthesiology and Critical Care, Heart and Diabetes Centre Mecklenburg-Vorpommern, Karlsburg, Germany
^b Departments of Thoracic and Cardiovascular Surgery, Heart and Diabetes Centre Mecklenburg-Vorpommern, Karlsburg, Germany
^c Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany

Accepted for publication September 19, 2000.

Address reprint requests to Dr Greinacher, Ernst-Moritz-Arndt Universität, Institut für Immunologie und Transfusionsmedizin, Klinikum/Sauerbruchstrasse, 17489 Greifswald, Germany

	Abstract

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We present a case of emergency coronary artery bypass surgery in a bilaterally nephrectomized patient with a history of heparin-induced thrombocytopenia. The patient was reexposed short term to heparin during cardiopulmonary bypass and did not develop any complications related to heparin-induced thrombocytopenia. Despite intraoperative neutralization of heparin severe bleeding complications occurred, probably resulting from preoperative therapeutic anticoagulation with r-hirudin in conjunction with an increased half-life of more than 2 days.

	Introduction

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Heparin-induced thrombocytopenia (HIT) is a rare but serious complication of heparin therapy. The mechanism involves the development of antibodies binding to heparin/platelet factor–4 complexes with consecutive activation of platelets, thromboembolic complications, and decrease in platelet counts. Immediate cessation of heparin and alternative anticoagulation are essential when HIT develops [1].

Heparin-induced thrombocytopenia antibodies are transient and become undetectable in the majority of cases about 6 weeks after the acute episode. Short-term reexposure to heparin in patients who do not have circulating HIT antibodies should be safe as long as heparin is strictly avoided before and after heparin administration because boostering of new HIT antibodies requires several days [2, 3]. We present a patient with a history of bilateral nephrectomy and HIT who needed emergency coronary artery bypass grafting. Anticoagulation during cardiopulmonary bypass (CPB) was performed with heparin rather than alternative anticoagulants.

A 60-year-old man with a history of bilateral nephrectomy had been on chronic intermittent hemodialysis using a standard heparin regimen for 10 years. Twelve months before the reported episode HIT was clinically suspected and serologically proved by the heparin-induced platelet activation assay (HIPA) after the occurrence of white clots in the extracorporeal circuit after vascular dialysis access surgery. Since then r-hirudin applied as a predialysis bolus of 5 mg for each session three times weekly had been used without any bleeding or clotting problems.

An acute coronary syndrome mandated therapeutic anticoagulation with a daily bolus of 3 to 5 mg of r-hirudin, which raised the activated partial thromboplastin time (aPTT) values to 60 to 90 seconds. Because of worsening symptoms the patient was required to undergo emergency coronary artery bypass grafting 8 days after starting therapeutic anticoagulation and 6 hours after the last 4-mg hirudin bolus had been given. Preoperative aPTT was 91 seconds.

For anticoagulation on CPB heparin was used according to standard protocol. After successful weaning from CPB heparin was neutralized by protamine. However major bleeding was observed intraoperatively and continued postoperatively. Chest drain output amounted to 4,820 mL within the first 5 hours postoperatively and required massive transfusion (18 U of packed red cells, 23 U of fresh frozen plasma, 2 U of platelet, and 3000 U of prothrombin complex concentrate).

Renal replacement therapy was performed by hemofiltration intraoperatively and between postoperative days 2 and 6. Because aPTT remained elevated no further anticoagulants were administered for hemofiltration. Hemodialysis was restarted on postoperative day 7 after a single 4-mg bolus of r-hirudin (Fig 1).

View larger version (19K): [in this window] [in a new window]   Fig 1. Platelet counts (filled circles), activated partial thromboplastin time (aPTT) values (filled squares), renal replacement therapy and parenteral anticoagulation preoperatively until day 10 in a bilaterally nephrectomized patient. The aPTT values were prolonged preoperatively due to preoperative therapeutic anticoagulation with r-hirudin doses of 3 to 5 mg daily for 8 days and decreased slowly despite postoperative hemofiltration (79 hours total, blood flow 120 to 150 mL/min, plasma water exchange 1500 mL/h, polysulphone high-efficiency hemofilter, Baxter Healthcare Corporation, Irvine, CA). As heparin had been neutralized by protamine directly after cardiopulmonary bypass (CPB), the prolonged aPTT was most likely caused by the hirudin given preoperatively.

The patient was transferred to a regular medical ward on postoperative day 10 and did not develop any further complications.

	Comment

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This case demonstrates that short-term reexposure to heparin is possible in patients with a history of HIT. Heparin-induced thrombocytopenia antibodies are transient and usually disappear from circulation about 6 weeks after the last heparin dose [4]. In a retrospective analysis of 119 HIT patients we could show that in cases of heparin reexposure after 3 months the induction of HIT antibodies follows the same pattern as when the patients were first exposed to heparin [5], ie, occurrence from day 5 of heparin treatment.

In the present case the risk of reexposure to heparin had to be weighed against the risks of using r-hirudin or danaparoid during CPB:

1. No antidote is available for either of these alternative anticoagulants in HIT.
   
2. Nonroutine laboratory assays (ecarin clotting time and antifactor Xa-activity respectively) were not available for monitoring in the emergency situation.
   
3. The pharmacokinetics of both substances depend on renal function.
   

The use of these alternative anticoagulants with their long and uncertain half-lives would have included a high risk of bleeding complications in our patient with no renal function [6]. We had to consider that aPTT values had already been prolonged because of preoperative therapeutic anticoagulation with hirudin.

This led to the management strategy of short-term heparin exposure during CPB with strict avoidance of heparin both pre- and postoperatively. As no HIT antibodies were present in the patient’s serum preoperatively, no immediate ill effects were to be expected. A possible boostering effect as demonstrated by the transiently positive HIPA assay results between day 7 to 12 was of no consequence, as no heparin was present at that time to form the antigen and the immune complexes that trigger the activation cascade leading to the clinical picture of HIT.

This case was not meant to recommend a strategy of concomitant use of hirudin and heparin to dampen potential HIT-related symptoms. In fact it provides further evidence that hirudin should be used with great caution in patients with renal impairment.

The course was complicated by enhanced bleeding that was most likely due to a prolonged effect of preoperatively given r-hirudin, as indicated by the prolonged aPTT despite heparin neutralization. Although r-hirudin elimination by hemofiltration in vitro has been demonstrated previously [7], removal of r-hirudin preoperatively given was not effective in our patient probably due to preoperative distribution in the interstitial fluid and prolonged redistribution even after cessation of r-hirudin. We therefore speculate that in this patient who developed severe bleeding complications despite antagonization of heparin the use of r-hirudin or danaparoid during CPB would have led to uncontrollable bleeding. Thus we consider this case to have been successfully managed despite the occurrence of bleeding complications.

We conclude that in patients with a history of HIT more than 3 months previously, short-term heparin reexposure can be a strategy to manage CPB, especially in patients with an increased risk of adverse effects of alternative anticoagulation such as impaired renal function. It is important to note that circulating HIT antibodies must be excluded before such a strategy is used.

	References

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1. Greinacher A., Warkentin T.E. Treatment of heparin-induced thrombocytopenia: an overview. In: Warkentin T.E., Greinacher A., eds. Heparin-induced thrombocytopenia. New York: Marcel Dekker, 2000:261-290.
2. Pötzsch B., Klovekorn W.P., Madlener K. Use of heparin during cardiopulmonary bypass in patients with a history of heparin-induced thrombocytopenia. N Engl J Med 2000;343:515.[Free Full Text]
3. Olinger G.N., Hussey C.V., Olive J.A., Malik M.I. Cardiopulmonary bypass for patients with previously documented heparin-induced platelet aggregation. J Thorac Cardiovasc Surg 1984;87:673-677.[Abstract]
4. Warkentin T.E., Kelton J.G. Timing of heparin-induced thrombocytopenia (HIT) in relation to previous heparin use: absence of an anamnestic immune response, and implications for repeat heparin use in patients with a history of HIT. Blood 1998;92(Suppl I):182a.
5. Kempf R., Eichner A., Lubenow N., Ranze O., Greinacher A. Heparin-induced thrombocytopenia: temporal pattern of platelet counts in patients being firstly exposed or reexposed to heparin. Ann Hematol 2000;79(Suppl I):A92.
6. Koster A., Pasic M., Bauer M., Kuppe H., Hetzer R. Hirudin as anticoagulant for cardiopulmonary bypass: importance of preoperative renal function. Ann Thorac Surg 2000;69:37-41.[Abstract/Free Full Text]
7. Frank R.D., Farber H., Stefanidis I., Lanzmich R., Kierdorf H.P. Hirudin elimination by hemofiltration: a comparative in vitro study of different membranes. Kidney Int 1999;56(Suppl 72):S41-S45.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Selleng, S. Articles by Greinacher, A. Search for Related Content PubMed PubMed Citation Articles by Selleng, S. Articles by Greinacher, A. Related Collections Extracorporeal circulation