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Ann Thorac Surg 1997;64:1059-1062
© 1997 The Society of Thoracic Surgeons

Original Article: Cardiovascular

Coronary Artery Bypass Grafting in Immune Thrombocytopenic Purpura

Thomas C. Mathew, MD, Ramadas Vasudevan, MD, Laszlo Leb, MD, Stephen M. Pezzella, MD, A. Thomas Pezzella, MD

Department of Medicine and Divisions of Cardiology, Hematology/Oncology, and Cardiothoracic Surgery, Saint Vincent Hospital and University of Massachusetts Medical School, Worcester, Massachusetts

Accepted for publication April 11, 1997.


   Abstract
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 Footnotes
 Abstract
Introduction
 Case Reports
 Comment
 Acknowledgments
 References
 
Background. Reports of patients with idiopathic thrombocytopenic purpura undergoing cardiac operations are scarce and no recommendations exist regarding their management. We report 3 patients with idiopathic thrombocytopenic purpura and severe coronary artery disease who underwent uncomplicated coronary bypass grafting.

Methods. The case history of each patient with idiopathic thrombocytopenic purpura who underwent coronary artery bypass grafting and the literature were reviewed.

Results. All 3 patients underwent uncomplicated coronary artery bypass grafting after preoperative treatment with intravenous immunoglobulin and intraoperative platelet transfusions if needed. Prophylactic splenectomy was not performed. There was no increased incidence of bleeding complications.

Conclusions. Coronary artery bypass grafting can be safely performed in patients with idiopathic thrombocytopenic purpura using conventional conduits after pretreating with immunoglobulin G and avoiding splenectomy.


   Introduction
Top
 Footnotes
 Abstract
 Introduction
Case Reports
 Comment
 Acknowledgments
 References
 
Cardiac operations requiring cardiopulmonary bypass have been safely performed in patients with a variety of hematologic disorders but reports on patients with idiopathic thrombocytopenic purpura (ITP) are scarce. Twenty such cases have been reported, 12 of which are in the Japanese literature; only 8 cases involved coronary artery bypass grafting (Table 1Go) [1–19]. We report a series of 3 nonsplenectomized patients with ITP who underwent successful coronary artery bypass grafting after intravenous immunoglobulin therapy.


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  		Table 1. . Review of Reported Cases of Idiopathic Thrombocytopenic Purpura Undergoing Cardiac Operation
 

   Case Reports
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 Abstract
 Introduction
 Case Reports
Comment
 Acknowledgments
 References
 
Patient 1
A 72-year-old man with long-standing ITP was admitted with a non–Q-wave myocardial infarction and mild congestive heart failure. Several years ago, owing to platelet counts as low as 15,000/µL, he was treated with glucocorticoids, which had to be discontinued after 6 months when platelet counts stabilized at 40,000/µL but side effects to steroids started to appear. Platelet count at the time of the current admission was 40,000/µL. Postinfarct angina necessitated cardiac catheterization for which he received 2 days of intravenous immunoglobulin therapy at 1 g • kg-1 • day-1 resulting in an increase of platelet count to 57,000/µL (Fig 1Go). He had critical multivessel coronary artery disease including significant left main stenosis; an intraaortic balloon pump was inserted and he was transferred to the coronary care unit awaiting coronary artery bypass grafting. Subsequently, pulmonary edema developed requiring intubation and mechanical ventilation, after which he underwent emergent coronary artery bypass grafting; saphenous vein grafts were placed to the posterior descending artery, left anterior descending artery, and obtuse marginal branch of the circumflex coronary artery. Cardiopulmonary bypass time was 197 minutes and aortic cross-clamp time was 133 minutes; seven units of platelets were transfused intraoperatively because platelet count dropped as low as 24,000/µL during cardiopulmonary bypass (Fig 2Go). The perioperative period was uneventful, without excessive bleeding; chest tubes were removed on the third postoperative day with a cumulative drainage of 590 mL. Platelet counts remained stable throughout this period and he was discharged on postoperative day 7. Platelet count on discharge was 137,000/µL.



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  		Fig 1. . Platelet trends during hospitalization.

 


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  		Fig 2. . Intraoperative variations in platelet count.

 
Patient 2
A 72-year-old woman with a 15-year history of ITP was admitted with unstable angina. Two years before this admission, with a baseline count of 30,000/µL, she was given a trial of glucorticoids but this was discontinued due to significant intolerance. Subsequently, intravenous immunoglobulin was tried to assess the platelet response; two consecutive doses at 0.8 g • kg-1 • day-1 raised her platelet count from 40,000 to 200,000/µL. Clinical examination on admission was unremarkable; initial platelet count was 49,000/µL. Before cardiac catheterization, she received two consecutive days of intravenous immunoglobulin at 0.8 g • kg-1 • day-1 and her platelet count increased to 130,000/µL. She had significant multivessel coronary disease including left main disease. Preoperative platelet count was 168,000/µL; hence, further therapy for thrombocytopenia was deferred. The patient underwent uncomplicated bypass with saphenous vein grafts to the left anterior descending, diagonal, and posterior descending arteries. Cardiopulmonary bypass time was 89 minutes and aortic cross-clamp time was 40 minutes. Perioperative period was uneventful, without excessive bleeding; chest tubes were removed on the second postoperative day with a cumulative drainage of 286 mL and the patient was discharged home in stable condition on postoperative day 6. Platelet count on discharge was 154,000/µL.

Patient 3
A 69-year-old man with ITP and intolerance to glucocorticoids was admitted with an acute inferior myocardial infarction; thrombolytic therapy was deferred because of ITP; platelet count on admission was 65,000/µL. Subsequently, he underwent uncomplicated cardiac catheterization, which revealed severe multivessel coronary artery disease. After the procedure, the platelet count dropped to 30,000/µL, but he remained asymptomatic. Before bypass grafting, he received 2 days of intravenous immunoglobulin therapy at 0.8 g • kg-1 • day-1, resulting in elevation of platelet count to 87,000/µL. At operation, he received venous grafts to the left anterior descending artery, posterior descending artery, and the obtuse marginal branch of the circumflex artery. Cardiopulmonary bypass time and aortic cross-clamp times were 124 and 67 minutes, respectively; six units of platelets were transfused intraoperatively because platelet count dropped to 57,000/µL on cardiopulmonary bypass. The perioperative period was uneventful without excessive bleeding; chest tubes were removed on the third postoperative day with a cumulative drainage of 1,380 mL. Platelet counts remained stable at greater than 100,000/µL and he was discharged in stable condition on postoperative day 8.


   Comment
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 Footnotes
 Abstract
 Introduction
 Case Reports
 Comment
Acknowledgments
 References
 
All 3 patients presented in this report had primary immune thrombocytopenic purpura. This diagnosis was made because of chronic thrombocytopenia with normal bone marrow morphology, adequate number of nondysplastic megakaryocytes, lack of splenomegaly, and the absence of any identifiable cause of secondary thrombocytopenia (eg, drugs, infections, collagen vascular disease, lymphoproliferative disease).

Most patients with chronic ITP are adults; 72% of patients more than 10 years of age are women and 70% of these are less than 40 years old [20]. Onset of thrombocytopenia is insidious with unremarkable history and physical examination except for manifestations of bleeding secondary to thrombocytopenia, including purpura, ecchymosis, epistaxis, and gingival bleeding, less commonly mucosal bleeding (ie, hematuria and gastrointestinal bleeding), and rarely intracerebral hemorrhage. Bleeding requiring blood replacement or special medical measures are unusual with platelet counts greater than 10,000/µL [21]. However, the risks of hemorrhagic complications and death are higher in elderly patients.

Idiopathic thrombocytopenic purpura is primarily a disorder of increased platelet destruction mediated by autoantibodies to platelet-membrane antigens. Recently, relative marrow failure, probably mediated by an effect of the antibodies on megakaryocytes has also been implicated as a contributing factor as platelet production is not appropriately increased in most patients. Autoantibodies that are reactive with major membrane glycoproteins are identifiable in about 80% of patients; most are directed against epitopes on glycoprotein IIb/IIIa, the most abundant and immunogenic platelet-surface glycoprotein, and less commonly against epitopes on glycoprotein Ib/V/IX, glycoprotein Ia/IIa, and glycoprotein IV; many react with more than one glycoprotein [22, 23]. Subsequently, the antibody-coated platelets are prematurely removed from the circulation by attachment to macrophage Fc receptors followed by phagocytosis.

Patients with asymptomatic mild or moderate thrombocytopenia can be followed up with no treatment as platelet counts greater than 50,000/µL are usually not associated with spontaneous clinically important bleeding; such patients can safely undergo invasive procedures [21]. Glucocorticoids (prednisone 1 mg/kg body weight) is the conventional initial modality of treatment for more severe thrombocytopenia (<30,000/µL), and usually produces a significant response within 1 to 2 weeks in about 70% of patients; relapses are common when the glucocorticoid dosage is reduced. Splenectomy had been in vogue for more that 30 years before the introduction of glucocorticoids in 1950, with low mortality in otherwise healthy patients but subsequently, was reserved for patients refractory to glucorticoids with a clinical response of 60%. Response to splenectomy typically occurs within several days. Other available treatment options include intravenous immune globulin, azathioprine, cyclophosphamide, and danazol. Platelet transfusion is useful in instances of severe hemorrhage, although it may be short acting [24]. Unlike all other therapeutic modalities, infusion of intravenous immunoglobulin has an immediate effect in increasing the platelet count and therefore is preferred when a rapid increase in platelet count is desired, as for instance in preparing patients for various surgical procedures. The major effect of immunoglobulin is probably mediated by blockade of macrophage Fc receptors; as a result, the antibody-coated platelets do not attach to macrophages, avoiding destruction by phagocytosis [25].

Immunoglobulin is administered in a total dose of 2 g/kg and can be given either in a 2- or 5-day schedule with similar results. Commercially available human immune globulin (eg, Sandoglobulin, Sandoz Pharmaceuticals, East Hanover, NJ; Gamimune, Bayer Pharmaceutical, West Haven, CT) is a sterile, highly purified polyvalent antibody product containing in concentrated form all the immoglobulin G antibodies that regularly occur in the donor population. It is produced by cold alcohol fractionation from the plasma of more than 16,000 United States donors. One hundred percent of the infused immunoglobulin G is available in the recipient circulation immediately after infusion. Contraindications to administration include patients with selective immunoglobulin A deficiency who possess antibodies to immunoglobulin A and those with severe systemic reactions to parenteral human immunoglobulin G. Adverse reactions are rare and occur in less than 1% of nonimmunodeficient patients and include headache, facial flushing, lightheadedness, chills, fever, nausea, diaphoresis, and hypotension; these are mostly relieved by temporarily stopping the drug infusion. There have been rare instances of transmission of hepatitis C and B in the past but that risk is nonexistent today because of rigorous virucidal and other quality control and screening measures. There are no documented cases of transmission of human immunodeficiency virus disease.

Data regarding patients with ITP undergoing cardiac operations are limited, and conflicting recommendations exist regarding management of such patients. Prophylactic splenectomy in the presence of significant coronary artery disease is associated with an increased risk of intraoperative cardiac morbidity and is probably not a viable option in most situations. To the best of our knowledge, there are currently 20 reported cases of patients with ITP undergoing cardiac operation (Table 1Go), of which only 8 involved coronary bypass. Our patients were all nonsplenectomized and did not get perioperative glucocorticoids, but instead received standard dosages of intravenous immunoglobulin. Intraoperative platelet transfusions were used in 2 patients because of sudden drop in platelet counts most probably related to accelerated consumption by the cardiopulmonary bypass machine. Cardiopulmonary bypass and operation were tolerated extremely well without any significant complications. Therefore, we suggest that intravenous immunoglobulin administration becomes the treatment of choice for patients with ITP undergoing cardiac operation. Moreover, given the minimal bleeding rate, extending the conduit use to include internal mammary arteries appears appropriate.


   Acknowledgments
Top
 Footnotes
 Abstract
 Introduction
 Case Reports
 Comment
 Acknowledgments
References
 
We thank Robert Yanagisawa, MD (Miriam Hospital, Brown University, Providence, Rhode Island), for help in manuscript preparation.


   Footnotes
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 Footnotes
Abstract
 Introduction
 Case Reports
 Comment
 Acknowledgments
 References
 
Address reprint requests to Dr Pezzella, Division of Cardiothoracic Surgery, Saint Vincent Hospital, 25 Winthrop St, Worcester, MA 01604.


   References
Top
 Footnotes
 Abstract
 Introduction
 Case Reports
 Comment
 Acknowledgments
 References
 

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  6. Koike R, Suma H, Oku T, Satoh H, Sawada Y, Takeuchi A. Combined coronary revascularization and splenectomy. Ann Thorac Surg 1989;48:853–4.[Abstract]
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  9. Yamashita M, Kawashima S, Miyazaki T, et al. Atrial septal defect with idiopathic thrombocytopenic purpura: a case of open heart surgery. Jpn J Thorac Surg 1990;43:401–3.
  10. Richards KM, Ferraris VA. Mitral valve replacement in a patient with idiopathic thrombocytopenic purpura: preoperative treatment with danazol. J Cardiovasc Surg 1991;32:840–2.[Medline]
  11. Jubelirer SJ. Coronary artery bypass in two patients with immune thrombocytopenic purpura without preoperative splenectomy. WV Med J 1992;88:510–1.
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