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Ann Thorac Surg 2001;72:1730-1732
© 2001 The Society of Thoracic Surgeons

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Case report

Off-pump coronary artery bypass grafting for acute heparin-induced thrombocytopenia

^a Departments of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
^b Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
^c Department of Cardiac Surgery, McMaster University, Hamilton, Ontario, Canada

Accepted for publication December 14, 2000.

* Address reprint requests to Dr Cybulsky, Department of Cardiac Surgery, McMaster University, 7th Floor, Hamilton General Hospital, McMaster Clinic, 237 Barton St East, Hamilton, ON L8L 2X2, Canada
e-mail: cybulsky{at}mcmaster.ca

	Abstract

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Surgical revascularization of coronary arteries is problematic for patients with heparin-induced thrombocytopenia because the available nonheparin anticoagulants cannot be reversed pharmacologically. We used three-vessel off-pump coronary artery bypass grafting in a patient with heparin-induced thrombocytopenia, as it allowed us to use substantially lower doses of nonheparin anticoagulant (danaparoid sodium), compared with procedures requiring cardiopulmonary bypass.

	Introduction

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Management of cardiac operations for patients with acute heparin-induced thrombocytopenia (HIT) is problematic. Alternative, nonheparin anticoagulants to permit cardiopulmonary bypass (CPB), such as danaparoid sodium, lepirudin, and argatroban, have been used, but each has limitations [1, 2]. In particular, the lack of antidotes for these agents means that severe postoperative bleeding can occur. For that reason, off-pump coronary artery bypass grafting might be a reasonable option in an otherwise suitable patient with acute HIT, as lower doses of anticoagulation can be given, compared with procedures using CPB [3]. We report successful use of danaparoid anticoagulation for off-pump coronary artery bypass grafting.

A 70-year-old woman with a remote anterior wall myocardial infarction was admitted to the hospital with a non-q wave myocardial infarction. Therapeutic-dose unfractionated heparin was given for 5 days and stopped. Because of recurrent angina, heparin was restarted on day 11 and continued for 9 days. Cardiac catheterization showed chronic occlusion of the proximal left anterior descending artery and tight stenosis of a large diagonal branch and the right coronary artery. From days 11 to 20, her platelet count decreased by 60% from 335 to 133 x 10⁹/L. Testing for heparin-dependent antibodies was strongly positive by both the platelet serotonin release assay and heparin/platelet factor 4 immunoassay.

Because of ongoing angina, a nonheparin anticoagulant, danaparoid, was given for 6 days at doses to maintain therapeutic levels (mean antifactor Xa level achieved, 0.54 U/mL). The platelet count recovered to 228 x 10⁹/L. Danaparoid was held 30 hours preoperatively.

Coronary artery bypass grafting was done using the off-pump (beating heart) technique, with the Octopus Tissue Stabilizer System (Medtronic Inc, Minneapolis, MN) with three grafts (left internal mammary artery to left anterior descending artery and saphenous vein grafts to diagonal artery and the posterior descending branch of the right coronary artery).

When the left internal mammary artery was being harvested, therapeutic-dose anticoagulation with danaparoid was started (initial 2,250-U intravenous bolus plus infusion at 150 U/h). Antifactor Xa levels were measured every 15 minutes by chromogenic assay (STA Rotachrom heparin kit; Diagnostica Stago, Asnieres-sur-Seine, France), using an Amax CS190 Plus analyzer (Sigma Diagnostics/Amelung GmbH, Lemgo, Germany) with a 10-minute turnaround time. A 750-U danaparoid booster dose was given once to maintain the target antifactor Xa level at or above 0.6 U/mL. The danaparoid infusion was stopped 45 minutes before the end of the operation. A total of 3,375 U of danaparoid was given intraoperatively.

Cardiopulmonary bypass standby was available, if required, with sufficient danaparoid available to have given the following additional doses: 2,250 U intravenous bolus; 3,000 U to the priming solution; and infusion rate increase to 200 U/h (target antifactor Xa level for CPB, > 1.5 U/mL, as recommended [2].)

Two units of red blood cell concentrates and 500 mL of plasma were given intraoperatively. Moderate postoperative chest tube drainage occurred (340 mL during the first 6 hours; 1,170 mL during the next 18 hours), and persistent oozing from the leg incision was observed. After an overnight hemoglobin decrease from 103 to 69 g/L, two additional units of red blood cell concentrates were given. Antithrombotic prophylaxis with danaparoid (750 U twice daily by subcutaneous injection) was given from day 2 until discharge on day 7. The postoperative course was uneventful, and HIT antibodies remained detectable at 1 month follow-up.

	Comment

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There are few options for patients with acute HIT who require heart operations. One option is to wait for the HIT antibodies to become undetectable, and then to operate using a brief intraoperative exposure to heparin [2, 4]. This approach is not suitable for an unstable patient, however, as it might take several months for antibody levels to decline sufficiently [4]. A second option is to perform heart operations using the recombinant antithrombin, lepirudin [2, 5]. Although use of lepirudin monitored by activated partial thromboplastin time seemed reasonable for off-pump procedures, we were concerned that our patient might still have required CPB for technical reasons, and activated partial thromboplastin time monitoring is inadequate to monitor the higher doses of lepirudin required for CPB [2]. We did not have the appropriate test (ecarin clotting time) [2, 5] to monitor this situation.

Danaparoid sodium is a mixture of anticoagulant glycosaminoglycans ("heparinoid") with predominant antifactor Xa activity that is widely used for treatment of HIT. Danaparoid has also been used for heart operations with CPB [1, 2], but the large doses required for this indication (about 18,000 U per procedure [1]), the long half-life of danaparoid (about 25 hours), and the inability to reverse its anticoagulant action, are major drawbacks. A review [1] of 47 patients who received danaparoid for CPB found that 36% required reoperation for bleeding, and 43% received 13 or more units of blood product.

The danaparoid dosing protocol we used for off-pump coronary artery bypass grafting was similar to that recommended for HIT patients who have peripheral vascular operations, and it resulted in stable intraoperative anticoagulation in our patient (Table 1). Only 3,375 U of danaparoid were needed to reach and maintain the target level of anticoagulation (0.6 U/mL), which was one-fifth the usual dose of danaparoid needed for CPB [1, 2, 6] where the target level of anticoagulation is much higher (> 1.5 U/mL) [1, 2].

	Footnotes

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	References

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1. Magnani H.N., Beijering R.J.R., ten Cate J.W., Chong B.H. Orgaran anticoagulation for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. In: Pifarré R., ed. New anticoagulants for the cardiovascular patient. Philadelphia: Hanley & Belfus, Inc, 1997:487-500.
2. Poetzsch B., Madlener K. Management of cardiopulmonary bypass anticoagulation in patients with heparin-induced thrombocytopenia. In: Warkentin T.E., Greinacher A., eds. Heparin-induced thrombocytopenia. New York: Marcel Dekker Inc, 2000:355-369.
3. Dagenais F., Perrault L.P., Cartier R., Searle N., Pagé P., Pellerin M., Pelletier L.C., Carrier M. Beating heart coronary artery bypass grafting: technical aspects and results in 200 patients. Can J Cardiol 1999;15:867-872.[Medline]
4. Pötzsch B., Klövekorn W.P., Madlener K. Use of heparin during cardiopulmonary bypass in patients with a history of heparin-induced thrombocytopenia. N Engl J Med 2000;343:7.
5. Koster A., Loebe M., Hansen R., et al. A quick assay for monitoring recombinant hirudin during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II: adaptation of the ecarin clotting time to the ACT II device. J Thorac Cardiovasc Surg 2000;119:1278-1283.[Abstract/Free Full Text]
6. Greinacher A., Warkentin T.E. Treatment for heparin-induced thrombocytopenia: an overview. In: Warkentin T.E., Greinacher A., eds. Heparin-induced thrombocytopenia. New York: Marcel Dekker, Inc, 2000:261-290.

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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 Author home page(s): Irene J. Cybulsky Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Warkentin, T. E. Articles by Cybulsky, I. J. Search for Related Content PubMed PubMed Citation Articles by Warkentin, T. E. Articles by Cybulsky, I. J. Related Collections Coronary disease