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Ann Thorac Surg 1999;68:576-578
© 1999 The Society of Thoracic Surgeons

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Case Reports

Heparin-induced thrombocytopenia in coronary bypass surgery

^a Surgery, Medical Colle of Pennsylvania, Hahnemann School of Medicine, Philadelphia, Pennsylvania, USA
^b Cardiothoracic Surgery, Medical College of Pennsylvania, Hahnemann School of Medicine, Philadelphia, Pennsylvania, USA

Address reprint requests to Dr Arnoletti, Department of Surgery, MCP-Hahnemann School of Medicine, Broad and Vine Sts, Philadelphia, PA 19102
e-mail: jupablo{at}pol.net

	Abstract

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We report on a 51-year-old man with severe two-vessel coronary disease and an ejection fraction of 15% who presented with myocardial ischemia and heparin-induced thrombocytopenia after coronary angioplasty. Before coronary bypass surgery, the antithrombin agent argatroban was used for anticoagulation and an intra-aortic balloon pump was inserted. Direct coronary bypass surgery was performed to the left anterior descending artery and to the posterior descending artery using the ‘Octopus’ tissue stabilization device (Manfrotto, Feltre, Italy). The postoperative course was uneventful and associated with normal platelet counts. The patient was discharged on the 6th postoperative day.

	Introduction

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Heparin-induced thrombocytopenia (HIT) occurs in 3%–5% of patients exposed to unfractionated heparin. This immunoglobulin-mediated adverse drug reaction is associated with thrombotic complications in 30%–80% of cases [1–3]. The pathogenic antibody (HIT-IgG) recognizes a multimolecular complex of heparin and platelet factor 4, resulting in platelet activation. Thrombocytopenia caused by HIT-IgG typically begins 5 to 8 days after starting heparin therapy, sooner if the patient has received heparin during the previous 3 months [1]. The currently accepted method of detecting HIT antibody is the serotonin release assay although other methods, including an enzyme linked immuno-sorbent assay (ELISA), have been described [2].

Open heart surgery in the presence of HIT poses a therapeutic dilemma. Although heparin substitutes such as r-hirudin and Orgaran (danaparoid sodium) have been successfully administered to heart surgery patients with HIT, utilization of heparin and aspirin as an anti-platelet agent is usually the regimen of choice, with acknowledgment of its thrombotic potential [2, 4].

Argatroban is a new synthetic thrombin inhibitor that offers several advantages over danaparoid sodium and hirudin. These include speed of action and selectivity for the catalytic site of thrombin, and it has been used as an alternative anticoagulant agent during coronary stent implantation in a patient with HIT [5, 6].

Direct coronary bypass surgery using the ‘Octopus’ tissue-stabilizing device (OTS) without cardiopulmonary bypass, has been shown to be safe and advantageous [7]. The OTS is a suction device that restrains anastomosis site motion to 1 x 1 mm and facilitates off-pump coronary surgery with well-tolerated hemodynamic effects. The OTS has been shown to be effective in patients with multivessel coronary disease [8].

A 51-year-old man (weight = 61kg; BSA = 1.7m²) presented with an occluded left anterior descending coronary artery and severely stenosed right coronary artery in the midst of an inferior wall infarct. His ejection fraction was estimated to be 15%. Angioplasty of the mid and distal right coronary artery was performed, with stent placement under systemic heparinization. Post-angioplasty recovery was uneventful. The patient returned 1 week after discharge with recurrent chest pain, inferior ST segment elevation, and a peak CPK of 250 U/L. Repeat cardiac catheterization revealed stenosis of the right coronary artery angioplasty site and a repeat angioplasty was performed. Four days later, despite systemic heparinization, he developed recurrent angina with electrocardiographic changes. Coincidentally, his platelet count dropped from 191 x 10³ platelets/µl to 62 x 10³ platelets/µl. Serotonin release assay and ELISA were positive for HIT-IgG. Heparin therapy was discontinued and intravenous argatroban was started after obtaining informed consent from the patient. A continuous argatroban infusion was subsequently maintained at a rate of 3µg/kg/min, keeping the aPTT between 1.5–3 times the control value. Two days later the patient was brought to the operating room for coronary bypass surgery. The argatroban infusion was discontinued 30 minutes prior to surgery.

Intraoperatively, an intraaortic balloon pump was inserted percutaneously prior to the performance of the median sternotomy. Utilizing the OTS, saphenous vein grafts were anastomosed to the left anterior descending and to the posterior descending arteries. A vessel loop to allow a dry field was only required for the posterior descending artery anastomosis and was placed proximal to the anastomotic site. Coronary ischemia times were 5 and 6 minutes, respectively. Retraction of the heart to perform the posterior anastomoses was well tolerated. The proximal aortic anastomoses were constructed utilizing a side-biting clamp. No anticoagulants were administered during the surgery, relying upon the residual anticoagulant argatroban effect. An aPTT obtained upon induction of anesthesia was 50.2 seconds, and 5 hours later the postoperative aPTT was normal at 35.6 seconds. After the patient was anesthetized and the intraaortic balloon pump had been placed, pulmonary artery diastolic pressure was 21 mm Hg with a cardiac index of 2.2 l/m². At the end of the surgery, pulmonary artery diastolic pressure was 27 mm Hg, generating a cardiac index of 2.2 L/m², on epinephrine infusion at 0.025 µg/kg/min, and with the intraaortic balloon pump set again at 1:1.

Immediately postoperatively, the patient’s hemoglobin concentration was 10.4 g/dL and his platelet count was 93 x 10³ platelets/µL. Chest tube output was 550 mL for the first 24 hours. The intraaortic balloon pump was removed on postoperative day 1 and the patient was extubated on that same day. Dobutamine infusion was started at 5 µg/kg/min and the epinephrine infusion was discontinued with a last known pulmonary artery diastolic pressure of 25 mm Hg and a cardiac index of 2.7 L/m². The dobutamine was weaned over the next 2 days and after an uneventful recovery, the patient was discharged home on the 6th postoperative day with a platelet count of 299 x 10³ platelets/µL (Fig 1).

View larger version (20K): [in this window] [in a new window]   Fig 1. Platelet count during hospital stay.

	Comment

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Danaparoid sodium, hirudin, and argatroban are the main heparin substitutes currently available. Danaparoid sodium is a mixture of anticoagulant glycosaminoglycans with predominant anti-factor Xa activity. Potential disadvantages of its use include difficulty in monitoring anticoagulant levels, cross-reactivity with HIT-IgG, and reported increased blood loss during cardiac surgery [1, 2, 9]. Hirudin is a potent direct thrombin inhibitor whose disadvantages include slow onset of action, irreversible effects, and high risk of bleeding in renal failure patients. Hirudin has been used as an effective heparin substitute in heart surgery patients [4]. Argatroban is a fast, reversible, direct thrombin inhibitor that is metabolized in the liver. Although no drug to reverse its anticoagulant effect is available, its plasma half-life is only 30 minutes and its anticoagulant effect can be monitored using the aPTT or ACT. No serious adverse effects have been described in patients receiving argatroban [5].

We report a patient with a typical presentation of HIT after repeated exposures to unfractionated heparin in successive hospital admissions and cardiac catheterization procedures. No thrombotic complications were detected and the diagnosis was confirmed by serotonin release assay and ELISA. Argatroban infusion provided adequate therapy for his coronary ischemia in the presence of HIT. His need for coronary bypass surgery posed a dilemma complicated by his poor ventricular function. The maximum therapeutic benefit of coronary surgery was obtained by performing direct revascularization without cardiopulmonary bypass. An occluded left anterior descending artery with a severely diseased right coronary artery provided a good indication to use the OTS. The argatroban infusion was stopped just prior to surgery and the anastomoses were performed in a short period of time with mild anticoagulation from the residual argatroban effect. With the assistance of the intra-aortic balloon pump, the patient’s hemodynamics remained stable throughout the surgery, even while the beating heart was retracted to expose the posterior descending artery. There were no postoperative complications.

This case presents several methodologies, all of which should be part of the therapeutic armamentarium available to surgeons who treat coronary artery disease in the setting of HIT. The combination of argatroban and multivessel direct coronary artery bypass grafting utilizing the OTS with intra-aortic balloon pump protection provides an example of new modalities available for approaching this type of high risk patient. Despite our success in employing this new methodology, the authors recognize that controlled studies are necessary to fully address the safety of argatroban in HIT patients who require cardiac surgery.

	References

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1. Warkentin T.E. Heparin-induced thrombocytopenia. Drug Saf 1997;17:325-341.[Medline]
2. Cancio L.C., Cohen D.J. Heparin-induced thrombocytopenia and thrombosis. J Am Coll Surg 1998;186:76-91.[Medline]
3. Warkentin T.E., Levine M.N., Hirsh J., et al. Heparin-induced thrombocytopenia in patients treated with low-molecular weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330-1335.[Medline]
4. Sodian R., Loebe M., Gorman K.F., Riess H., Hetzer R. Heparin induced thrombocytopenia. ASAIO Journal 1997;43:M430-M433.[Medline]
5. Hursting M.J., Alford K.L., Becker J.C.P., et al. Novastan (brand of argatroban). Semin Thromb Hemost 1997;23:503-516.[Medline]
6. Lewis B.E., Iaffaldano R., McKiernan T.L., Rao L., Donkin J., Wallenga J.M. Report of succesful use of argatroban as an alternative anticoagulant during coronary stent implantation in a patient with heparin-induced thrombocytopenia and thrombosis syndrome. Cathet Cardiovasc Diagn 1996;38:206-209.[Medline]
7. Jansen EWL, Grundeman PF, Borst, et al. Less invasive off-pump CABG using a suction device for immobilization: the ‘octopus’ method. Eur J Cardiothorac Surg 1997;12:406–12.
8. Hart J, Hayden A, Spoones T, Whitman G. Uniform safety of beating heart surgery utilizing the Octopus tissue stabilization system (OTS). Heart Surgery Forum 1999; in press.
9. Alving B.M., Krishnamurti C. Recognition and management of heparin-induced thrombocytopenia (HIT) and thrombosis. Semin Thromb Hemost 1997;23:569-574.[Medline]

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