Ann Thorac Surg 2000;70:2161-2163
© 2000 The Society of Thoracic Surgeons
Case report
Nafamostat mesilate treatment during open heart operation in immune thrombocytopenic purpura
Kunihide Nakamura, MDa,
Toshio Onitsuka, MDa,
Mitsuhiro Yano, MDa,
Hiroyuki Nagahama, MDa,
Eisaku Nakamura, MDa,
Yasunori Matsuzaki, MDa
a Department of Surgery 2, Miyazaki Medical College, Miyazaki, Japan
Accepted for publication February 4, 2000.
Address reprint requests to Dr Nakamura, Department of Surgery 2, Miyazaki Medical College, 5200, Kihara, Kiyotake, Miyazaki, Japan 889-1692
e-mail: shiori{at}post1.miyazaki-med.ac.jp
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Abstract
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A 58-year old woman with idiopathic thrombocytopenic purpura underwent mitral and aortic valve replacements and tricuspid annuloplasty. Preoperative therapeutic interventions including prednisone and immunoglobulin were successful in elevating the platelet count to 93,000/mm2. Furthermore, we used nafamostat mesilate for coagulopathy prophylaxis during cardiopulmonary bypass. Postoperative bleeding was average and clinical course was uneventful. The perioperative management for patients with idiopathic thrombocytopenic purpura requiring cardiac operation is reviewed.
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Introduction
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As cardiac operations require heparin for cardiopulmonary bypass (CPB) and platelet counts drop frequently most probably because of accelerated consumption by CPB, the operation must be performed carefully when a patient has a coagulation disorder. We report our management of a patient with valvular heart disease and idiopathic thrombocytopenic purpura (ITP) in whom perioperative hemostasis was supplemented with preoperative prednisone therapy and intraoperative use of nafamostat mesilate (NM), which is synthesized in Japan and is a broad-spectrum inhibitor of inflammatory response during cardiopulmonary bypass [1].
A 58-year-old woman was admitted to our hospital in March 1998 with a 2-year history of heart failure. The patient’s past medical history included 10 years of diabetes. Laboratory evaluation revealed extremely low platelet counts (47,000/mm3), with a hematocrit of 3.6%. Cardiothoracic ratio was 64% on her chest roentgenogram and atrial fibrillation was confirmed by electrocardiogram. An echocardiogram and a cardiac catheterization revealed aortic stenosis with a 40-mm Hg gradient across the aortic valve and severe mitral stenosis involving 1.1 cm2 of mitral valve area. Aortic regurgitation was mild, but both severe mitral and tricuspid regurgitation were noticed.
As the bone marrow aspirate demonstrated increased megakaryocyte with no cellular atypia, the patient was diagnosed as having ITP. The level of platelet-associated IgG was higher than normal. Prednisone therapy was started on April 30, 1998: prednisone 1,000 mg was administered in the course of pulse therapy for 3 days. Afterwards, maintenance treatment of prednisone 50 mg per day was started, then the dosage was gradually diminished beginning June 4 and finally 10 mg was administered on July 21, the operation day. The platelet counts maintained about 100,000/mm3. An insulin treatment was added because of the deterioration of the diabetes. High-dose immunoglobulin (400 mg/kg per day) was administered for 5 days just before the operation with no effect on platelet count. The platelet count was 93,000/mm3 on the operation day (Fig 1).
On July 21, 1998, the patient underwent mitral valve replacement with a #25 St. Jude Medical (SJM) mechanical prosthesis (St. Jude Medical, Minneapolis, MN), aortic valve replacement with a #21 SJM valve, and tricuspid annuloplasty. The cardiopulmonary bypass time was 196 minutes and the aortic cross-clamp time was 139 minutes. The patient was administered 17,100 U of heparin before CPB and NM (80 mg/h) was given during CPB. After neutralization of the heparin with protamine, 20 U of platelets were transfused intraoperatively because of concern about ITP. The postoperative course was uneventful. Chest tube drainage was 1,220 mL during 24 hours after the operation and the tube was removed on the fifth postoperative day (POD). The tracheal tube was extracted and the patient was treated again with prednisone therapy on the first POD. Although the platelet count decreased to 35,000/mm3, the lowest value, on the second POD, there was no administration of platelets subsequently. The patient’s platelet count was 130,000/mm3 on the 10th POD. The dosage of prednisone was diminished gradually and was discontinued on the 47th POD (Fig 1).
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Comment
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There are few reports of ITP in patients requiring open heart operation [2–5], so the perioperative treatment of ITP is uncertain. The most hazardous complication is intraoperative and postoperative bleeding due to platelet dysfunction. Several forms of therapy have been used for ITP including prednisone, splenectomy, danazol, and a variety of immunosuppressants [6]. Prednisone is usually the initial treatment in ITP. If the patient fails to respond to steroids, cytotoxic drugs (azathioprine or cyclophosphamide) are administered. Splenectomy is usually considered an alternative treatment for patients with ITP. High-dose intravenous immunoglobulin has been recommended as emergency treatment. This treatment incurs a rapid but usually transient increase of the platelet count, so this therapeutic modality is probably best used only to prepare a patient for an invasive procedure. Moreover, platelet transfusion is used in patients because of a sudden drop in platelet counts related to invasive operation or delivery and so forth on.
To the best of our knowledge, there are 24 cases of patients with ITP who underwent cardiac operation in 21 previously published studies, and 14 cases are Japanese. In these 24 cases, prednisone was administered in 10 cases, danazol in 3 cases, and an immunosuppressive agent in 1 case before cardiac operations. Splenectomy was carried out as the preoperative treatment in 2 cases. In 3 cases, cardiac operation and the splenectomy were performed simultaneously [2, 3], and the splenectomy had already been performed as a treatment of ITP in only 1 case. Immunoglobulin was used for 14 cases. The platelet transfusion was used for all but 2 cases [4]. Maronas and coworkers [3] believe that a two-stage surgical approach is preferable (first doing splenectomy followed by the necessary cardiac operation), but they performed the above two operations simultaneously. Mathew and coworkers [4] reported 3 patients with ITP and severe coronary artery disease who underwent coronary artery bypass grafting and they concluded that cardiac operation could be performed safely with the administration of immunoglobulin preoperatively and intraoperative platelet transfusion if needed. Jubelirer [5] described two successful coronary artery bypass graftings without splenectomy; he suggested that platelet transfusion may be an alternative to prophylactic splenectomy, and that the performance of splenectomy may be associated with an increased risk of intraoperative cardiac morbidity in patients with serious coronary artery disease.
Although the preoperative therapeutic purpose in ITP is not to normalize platelets but to maintain platelet counts, there is no clear value concerning the safety limits of platelet counts in cardiac operations. Three patients (from prior reports) with ITP underwent cardiac operation who had platelet counts of 50,000/mm3 or less and splenectomy was performed simultaneously in 2 cases [2, 3]. Moreover, 9 patients with ITP whose platelet counts were from 50,000 to 100,000/mm3 underwent cardiac operation safely. Based on 24 cases in 21 reports, for patients with ITP whose platelet count is 50,000/mm3 or more, cardiac operation may be performed safely with the use of intraoperative platelet transfusion.
Prophylactic aprotinin therapy has significant platelet protective effects and reduces blood loss in patients with intact hemostasis undergoing cardiac operation [7]. Recent studies showed that aprotinin appears to retain its beneficial effect in the presence of impaired hemostasis. Miyamoto and colleagues [1] reported NM reduced blood loss by preserving platelet and inhibiting fibrinolysis. Aprotinin is a complex polypeptide that is extracted from bovine lung or porcine gut and its half-time in the plasma is approximately 45 minutes. NM is a guanidine acid derivative and has a short plasma half-time (5 to 10 minutes). Aprotinin preserves platelet sensitivity to adenosine diphosphate, but, as with NM, reduced platelet ß-thromboglobulin (ß-TG) release and fails to prevent platelet adhesion [8]. Both protease inhibitors block kallikrein formation but the inhibition of neutrophil elastase release is more profound with NM than with aprotinin, suggesting that the decrease in ß-TG release may be related in part to suppression of neutrophil activation [8]. Despite some treatment, platelet counts are not normal in patients with ITP, therefore, the goal of NM administration is to prevent further abnormalities of coagulation during CPB to reduce the blood loss. Our case demonstrated that NM might be as effective as aprotinin for a defective hemostatic case.
In conclusion, prednisone and the immunoglobulin treatments were administered preoperatively for a patient who had valvular disease with ITP. Platelet transfusion and NM were used during the operation. The double valve replacement and tricuspid annuloplasty were performed successfully. NM was considered to be effective in cardiac operation for this patient who had the abnormality of hemostasis.
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References
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Miyamoto Y., Nakano S., Kaneko M., Takano H., Matsuda H. Clinical evaluation of a new synthetic protease inhibitor in open heart surgery. Effect on plasma serotonin and histamine release and blood conservation. ASAIO J 1992;38:M395-M398.[Medline]
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Koike R., Suma H., Oku T., Satoh H., Sawada Y., Takeuchi A. Combined coronary artery revascularization and splenectomy. Ann Thorac Surg 1989;48:853-854 Published erratum appears in Ann Thorac Surg 1990;50:514.[Abstract]
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Maronas J.M., Llamas P., Caffarena J.M. Mitral valve replacement and splenectomy in a patients with chronic idiopathic thrombocytopenic purpura. Thorac Cardiovasc Surg 1982;30:407-408.[Medline]
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Mathew T.C., Vasudevan R., Leb L., Pezzella S.M., Pezzella A.T. Coronary artery bypass grafting in immune thrombocytopenic purpura. Ann Thorac Surg 1997;64:1059-1062.[Abstract/Free Full Text]
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Jubelirer S.J. Coronary artery bypass in two patients with immune thrombocytopenic purpura without preoperative splenectomy. WV Med J 1992;88:510-511.
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Fujisawa K., Tani P., Piro L., McMillan R. The effect of therapy on platelet-associated autoantibody in chronic immune thrombocytopenic purpura. Blood 1993;81:2872-2877.[Abstract/Free Full Text]
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Van Oeveren W., Jansen N.J., Bidstrup B.P., et al. Effect of aprotinin on hemostatic mechanisms during cardiopulmonary bypass. Ann Thorac Surg 1987;44:640-645.[Abstract]
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Sundaram S., Gikakis N., Hack C.E., et al. Nafamostat mesilate, a broad spectrum protease inhibitor, modulates platelet, neutrophil, and contact activation in simulated extracorporeal circulation. Thromb Haemost 1996;75:76-82.[Medline]
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Abstract
Introduction
