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Thrombocytapheresis: Managing Essential Thrombocythemia in a Surgical Patient

2011; Elsevier BV; Volume: 92; Issue: 1 Linguagem: Inglês

10.1016/j.athoracsur.2011.02.050

1552-6259

Sudipta Sekhar Das, Satyajit Bose, Srirup Chatterjee, Ashok Parida, Suraj Kumar Pradhan,

Platelet Disorders and Treatments

A 73-year-old man presented with acute chest pain and shortness of breath suggestive of unstable angina. A detailed investigation revealed essential thrombocythemia and coronary artery pathology. With a baseline platelet count of 2,650 × 103/μL, coronary artery bypass grafting became nearly impossible. Three therapeutic plateletpheresis procedures successfully lowered the platelet count to 367 × 103/μL. Thereafter, surgery was performed with no complications. Although a drop and rise in platelet counts were observed postoperatively, the patient could be discharged in stable condition after 14 days. Thus, therapeutic plateletpheresis reduces platelet count rapidly in essential thrombocythemia and relieves patients of acute symptoms. A 73-year-old man presented with acute chest pain and shortness of breath suggestive of unstable angina. A detailed investigation revealed essential thrombocythemia and coronary artery pathology. With a baseline platelet count of 2,650 × 103/μL, coronary artery bypass grafting became nearly impossible. Three therapeutic plateletpheresis procedures successfully lowered the platelet count to 367 × 103/μL. Thereafter, surgery was performed with no complications. Although a drop and rise in platelet counts were observed postoperatively, the patient could be discharged in stable condition after 14 days. Thus, therapeutic plateletpheresis reduces platelet count rapidly in essential thrombocythemia and relieves patients of acute symptoms. Essential thrombocythemia (ET) is an uncommon type of chronic myeloproliferative disorder that predominantly occurs in middle-aged people and is characterized by clonal proliferation of megakaryocytes, which is caused by a defect of the early pluripotential or a more committed stem cell [1Tefferi A. Murphy S. Current opinion in essential thrombocythemia: pathogenesis, diagnosis, and management.Blood Rev. 2001; 15: 121-131Abstract Full Text PDF PubMed Scopus (87) Google Scholar, 2Harrison C.N. Green A.R. Essential thrombocythemia.Hematol Oncol Clin North Am. 2003; 17: 1175-1190Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar]. The common findings include high platelet counts in circulation, megakaryocyte hyperplasia, and clinical manifestations of both thrombotic and hemorrhagic diathesis and splenomegaly [3Mughal T.I. Primary thrombocythemia: a current perspective.Stem Cell. 1995; 13: 355-359Crossref PubMed Scopus (9) Google Scholar]. The diagnosis was confirmed on the basis of revised diagnostic criteria for essential thrombocythemia provided by the Polycythemia Vera Study Group, as described in a 1999 article by Michiels and colleagues [4Michiels J.J. Kutti J. Stark P. et al.Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thrombocythemia, polycythemia vera and essential megakaryocytic granulocytic metaplasia and myelofibrosis.Neth J Med. 1999; 54: 46-62Crossref PubMed Scopus (54) Google Scholar]. Although the treatment algorithm of ET includes drugs like hydroxyurea, anagrelide, or interferon-á for long-term management and therapeutic plateletpheresis of acute events, the treatment of uncomplicated ET is still a subject of debate [5Tefferi A. Recent progress in the pathogenesis and management of essential thrombocythemia.Leuk Res. 2001; 25: 369-377Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. Even more difficult is the management of patients with symptoms of ET and planning for cardiac surgery, because no definite guidelines are available in the literature discussing this issue. Here we present our experience of therapeutic plateletpheresis in an ET patient undergoing cardiac surgery for coronary occlusion with successful outcome.A 73-year-old man was referred to our cardiac science center with unstable angina. A detailed investigation revealed thrombosis of the left main coronary artery and left anterior descending coronary artery. Echocardiography showed ischemic cardiomyopathy, left ventricular dysfunction, and pulmonary arterial hypertension. The patient was a diabetic on oral treatment, and he had a history of anterior myocardial infarction 2 years ago for which he underwent primary angioplasty for myocardial infarction. Accordingly, an elective coronary artery bypass graft was planned. To our surprise, a routine investigation revealed a preoperative platelet count of 2,650 × 103/μL with other hematologic, coagulation, and biochemical measurements that were within a normal range. His inflammatory markers were negative. A repeat blood count on the next day also showed identical high platelet count. The patient had no past record of a platelet count, and a detailed medical history did not provide any additional information, except for occasional, mild headaches. A venous Doppler study showed no evidence of deep vein thrombosis or any venous incompetence. An ultrasonography revealed a normal sized spleen. Bone marrow showed slightly increased cellularity with adequate erythroid and myeloid lineages with foci of megakaryocytic hyperplasia with clustering of megakaryocytes (some which showed hyperploid nuclei). There was no evidence of reticulin fibrosis. Genetic study of the patient identified a mutation in the JAK2V617F gene with a normal cytogenetic (BCR-ABL) pattern. All of these investigations confirmed the diagnosis of high-risk ET that has triggered the onset of coronary thrombosis. Because coronary artery bypass grafting necessitates control of the patient's platelet count (during and after surgery) to reduce the risk of bleeding or thrombosis, oral hydroxyurea (1 gm/day) was immediately started. However, no response was noted, even after 2 weeks. Then, with a platelet count of 2,570 × 103/μL, the patient was referred to the transfusion medicine unit. Considering the severity of cardiac ailment and a significantly high platelet count, therapeutic platelet reduction using aphaeresis technology was planned to reduce the platelet count to less than 400 × 103/μL.Three therapeutic platelet reduction procedures were carried out on alternate days using the new generation cell separator Haemonetics MCS+ (Haemonetics Corp, Braintree, MA). All procedures were performed following the manufacturer's instructions using the therapeutic platelet reduction, dedicated closed system peripheral blood stem cell disposable set (Lot No. TT09083) and ACD-A as an anticoagulant. Whole blood volumes between 1,826 and 2,920 mL were processed with ACD-A usage between 188 and 264 mL without any adverse effects. We could reduce the patient platelet count to 367 × 103/μL at the end of the three procedures with reductions of 60%, 56.8%, and 41.9%, respectively, from the pre-procedure platelet count.The patient was taken for coronary artery bypass graft the next morning with a pre-surgical platelet count of 367 × 103/μL. There were no surgical or postsurgical complications, except a drop in platelet count to 167 × 103/μL on postoperative day 1. However, on postoperative day 5, the platelet count increased to 581 × 103/μL. A dose of hydroxyurea was raised to 2 gm/day with daily monitoring of the platelet count. The patient was stable and was discharged 14 days post-surgery on hydroxyurea (2 gm/day), with a platelet count of 356 × 103/μL (Fig 1). On follow-up, after 2 weeks, the patient was still stable with a reported platelet count of 284 × 103/μL.CommentThe usefulness of rapid plateletpheresis in preventing additional morbidity in patients with thrombocytosis by removing large numbers of circulating platelets has already been documented. Moreover, during cardiopulmonary bypass, activation and aggregation of platelets and a series of biochemical reactions produce thrombin that may lead to thrombosis within the circuit causing interruption of extracorporeal circulation, vital organ malperfusion, and thromboembolic complications [6Grima K.M. Therapeutic apheresis in hematological and oncological diseases.J Clin Apheresis. 2000; 15: 28-52Crossref PubMed Scopus (56) Google Scholar, 7Taft E.G. Babcock R.B. Scharfman W.B. Tartaglia A.P. Plateletpheresis in the management of thrombocytosis.Blood. 1977; 50: 927-933PubMed Google Scholar]. In the present study, reduction of a significantly high platelet count to less than 400 × 103/μL in a thin-built (48 kg) elderly man with unstable blood pressure seemed to be challenging, particularly with an underlying severe coronary artery disease. For optimum patient safety, we performed all therapeutic platelet reduction procedures under continuous cardiac monitoring and prophylactic injectable calcium to avoid citrate toxicity. The draw rate and return rate of each cycle were limited to 50 mL per minute and 70 mL per minute, respectively, with a maximum extracorporeal blood volume of 246 mL.Studies regarding performance of various cell separators used for therapeutic reduction of platelets in ET is scarce in the medical literature. Although Taft and colleagues [7Taft E.G. Babcock R.B. Scharfman W.B. Tartaglia A.P. Plateletpheresis in the management of thrombocytosis.Blood. 1977; 50: 927-933PubMed Google Scholar] were able to collect 16 × 1011 to 26 × 1011 platelets, and up to 98 × 1011 when processing volumes of more than 10 L by using the Haemonetics model 10 (Haemonetics Corp, Braintree, MA) and the Aminco Celltrifuge (American Instrument Company, Santa Ana, CA), McCarthy and colleagues [8McCarthy L.J. Graves V.L. Eigen H. McGuire W.A. Platelet apheresis for extreme thrombocytosis in an 11-year-old girl with CML.Transfus Med. 1991; 1: 187-189Crossref PubMed Scopus (15) Google Scholar] found a reduction between 1,580 × 103/μL and 2,665 × 103/μL of peripheral platelets by apheresis when using the CS-3000 Fenwal separator. The present study found the Haemonetics MCS+ to be highly efficient in the acute management of ET, and as low as three procedures could significantly reduce the platelet count and prepare the patient for coronary artery bypass grafting. However, lack of clear guidelines and the presence of a nonfunctional platelet in ET posed a problem in establishing a safe preoperative baseline platelet count in our patient. We observed that a preoperative platelet count between 350 × 103/μL and 400 × 103/μL was safe, which could take care of the surgery, as well as the postsurgical platelet loss. Also, it is a controversial issue whether this reduction is adequate for long-term maintenance, because rebound phenomena is common in ET, and this was been observed in our patient a few days after surgery. The patient could be followed for the next 7 months during which he had 11 hospital visits and had maintained a platelet count of 247 × 103/μL to 301 × 103/μL with oral hydroxyurea (500 gm/day).In conclusion, therapeutic plateletpheresis is a useful measure in reducing platelet count rapidly in ET and relieving patients of acute symptoms. However, such procedures should be performed very meticulously in an ET patient who has severe underlying cardiac disorder and needs for urgent surgery. Essential thrombocythemia (ET) is an uncommon type of chronic myeloproliferative disorder that predominantly occurs in middle-aged people and is characterized by clonal proliferation of megakaryocytes, which is caused by a defect of the early pluripotential or a more committed stem cell [1Tefferi A. Murphy S. Current opinion in essential thrombocythemia: pathogenesis, diagnosis, and management.Blood Rev. 2001; 15: 121-131Abstract Full Text PDF PubMed Scopus (87) Google Scholar, 2Harrison C.N. Green A.R. Essential thrombocythemia.Hematol Oncol Clin North Am. 2003; 17: 1175-1190Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar]. The common findings include high platelet counts in circulation, megakaryocyte hyperplasia, and clinical manifestations of both thrombotic and hemorrhagic diathesis and splenomegaly [3Mughal T.I. Primary thrombocythemia: a current perspective.Stem Cell. 1995; 13: 355-359Crossref PubMed Scopus (9) Google Scholar]. The diagnosis was confirmed on the basis of revised diagnostic criteria for essential thrombocythemia provided by the Polycythemia Vera Study Group, as described in a 1999 article by Michiels and colleagues [4Michiels J.J. Kutti J. Stark P. et al.Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thrombocythemia, polycythemia vera and essential megakaryocytic granulocytic metaplasia and myelofibrosis.Neth J Med. 1999; 54: 46-62Crossref PubMed Scopus (54) Google Scholar]. Although the treatment algorithm of ET includes drugs like hydroxyurea, anagrelide, or interferon-á for long-term management and therapeutic plateletpheresis of acute events, the treatment of uncomplicated ET is still a subject of debate [5Tefferi A. Recent progress in the pathogenesis and management of essential thrombocythemia.Leuk Res. 2001; 25: 369-377Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. Even more difficult is the management of patients with symptoms of ET and planning for cardiac surgery, because no definite guidelines are available in the literature discussing this issue. Here we present our experience of therapeutic plateletpheresis in an ET patient undergoing cardiac surgery for coronary occlusion with successful outcome. A 73-year-old man was referred to our cardiac science center with unstable angina. A detailed investigation revealed thrombosis of the left main coronary artery and left anterior descending coronary artery. Echocardiography showed ischemic cardiomyopathy, left ventricular dysfunction, and pulmonary arterial hypertension. The patient was a diabetic on oral treatment, and he had a history of anterior myocardial infarction 2 years ago for which he underwent primary angioplasty for myocardial infarction. Accordingly, an elective coronary artery bypass graft was planned. To our surprise, a routine investigation revealed a preoperative platelet count of 2,650 × 103/μL with other hematologic, coagulation, and biochemical measurements that were within a normal range. His inflammatory markers were negative. A repeat blood count on the next day also showed identical high platelet count. The patient had no past record of a platelet count, and a detailed medical history did not provide any additional information, except for occasional, mild headaches. A venous Doppler study showed no evidence of deep vein thrombosis or any venous incompetence. An ultrasonography revealed a normal sized spleen. Bone marrow showed slightly increased cellularity with adequate erythroid and myeloid lineages with foci of megakaryocytic hyperplasia with clustering of megakaryocytes (some which showed hyperploid nuclei). There was no evidence of reticulin fibrosis. Genetic study of the patient identified a mutation in the JAK2V617F gene with a normal cytogenetic (BCR-ABL) pattern. All of these investigations confirmed the diagnosis of high-risk ET that has triggered the onset of coronary thrombosis. Because coronary artery bypass grafting necessitates control of the patient's platelet count (during and after surgery) to reduce the risk of bleeding or thrombosis, oral hydroxyurea (1 gm/day) was immediately started. However, no response was noted, even after 2 weeks. Then, with a platelet count of 2,570 × 103/μL, the patient was referred to the transfusion medicine unit. Considering the severity of cardiac ailment and a significantly high platelet count, therapeutic platelet reduction using aphaeresis technology was planned to reduce the platelet count to less than 400 × 103/μL. Three therapeutic platelet reduction procedures were carried out on alternate days using the new generation cell separator Haemonetics MCS+ (Haemonetics Corp, Braintree, MA). All procedures were performed following the manufacturer's instructions using the therapeutic platelet reduction, dedicated closed system peripheral blood stem cell disposable set (Lot No. TT09083) and ACD-A as an anticoagulant. Whole blood volumes between 1,826 and 2,920 mL were processed with ACD-A usage between 188 and 264 mL without any adverse effects. We could reduce the patient platelet count to 367 × 103/μL at the end of the three procedures with reductions of 60%, 56.8%, and 41.9%, respectively, from the pre-procedure platelet count. The patient was taken for coronary artery bypass graft the next morning with a pre-surgical platelet count of 367 × 103/μL. There were no surgical or postsurgical complications, except a drop in platelet count to 167 × 103/μL on postoperative day 1. However, on postoperative day 5, the platelet count increased to 581 × 103/μL. A dose of hydroxyurea was raised to 2 gm/day with daily monitoring of the platelet count. The patient was stable and was discharged 14 days post-surgery on hydroxyurea (2 gm/day), with a platelet count of 356 × 103/μL (Fig 1). On follow-up, after 2 weeks, the patient was still stable with a reported platelet count of 284 × 103/μL. CommentThe usefulness of rapid plateletpheresis in preventing additional morbidity in patients with thrombocytosis by removing large numbers of circulating platelets has already been documented. Moreover, during cardiopulmonary bypass, activation and aggregation of platelets and a series of biochemical reactions produce thrombin that may lead to thrombosis within the circuit causing interruption of extracorporeal circulation, vital organ malperfusion, and thromboembolic complications [6Grima K.M. Therapeutic apheresis in hematological and oncological diseases.J Clin Apheresis. 2000; 15: 28-52Crossref PubMed Scopus (56) Google Scholar, 7Taft E.G. Babcock R.B. Scharfman W.B. Tartaglia A.P. Plateletpheresis in the management of thrombocytosis.Blood. 1977; 50: 927-933PubMed Google Scholar]. In the present study, reduction of a significantly high platelet count to less than 400 × 103/μL in a thin-built (48 kg) elderly man with unstable blood pressure seemed to be challenging, particularly with an underlying severe coronary artery disease. For optimum patient safety, we performed all therapeutic platelet reduction procedures under continuous cardiac monitoring and prophylactic injectable calcium to avoid citrate toxicity. The draw rate and return rate of each cycle were limited to 50 mL per minute and 70 mL per minute, respectively, with a maximum extracorporeal blood volume of 246 mL.Studies regarding performance of various cell separators used for therapeutic reduction of platelets in ET is scarce in the medical literature. Although Taft and colleagues [7Taft E.G. Babcock R.B. Scharfman W.B. Tartaglia A.P. Plateletpheresis in the management of thrombocytosis.Blood. 1977; 50: 927-933PubMed Google Scholar] were able to collect 16 × 1011 to 26 × 1011 platelets, and up to 98 × 1011 when processing volumes of more than 10 L by using the Haemonetics model 10 (Haemonetics Corp, Braintree, MA) and the Aminco Celltrifuge (American Instrument Company, Santa Ana, CA), McCarthy and colleagues [8McCarthy L.J. Graves V.L. Eigen H. McGuire W.A. Platelet apheresis for extreme thrombocytosis in an 11-year-old girl with CML.Transfus Med. 1991; 1: 187-189Crossref PubMed Scopus (15) Google Scholar] found a reduction between 1,580 × 103/μL and 2,665 × 103/μL of peripheral platelets by apheresis when using the CS-3000 Fenwal separator. The present study found the Haemonetics MCS+ to be highly efficient in the acute management of ET, and as low as three procedures could significantly reduce the platelet count and prepare the patient for coronary artery bypass grafting. However, lack of clear guidelines and the presence of a nonfunctional platelet in ET posed a problem in establishing a safe preoperative baseline platelet count in our patient. We observed that a preoperative platelet count between 350 × 103/μL and 400 × 103/μL was safe, which could take care of the surgery, as well as the postsurgical platelet loss. Also, it is a controversial issue whether this reduction is adequate for long-term maintenance, because rebound phenomena is common in ET, and this was been observed in our patient a few days after surgery. The patient could be followed for the next 7 months during which he had 11 hospital visits and had maintained a platelet count of 247 × 103/μL to 301 × 103/μL with oral hydroxyurea (500 gm/day).In conclusion, therapeutic plateletpheresis is a useful measure in reducing platelet count rapidly in ET and relieving patients of acute symptoms. However, such procedures should be performed very meticulously in an ET patient who has severe underlying cardiac disorder and needs for urgent surgery. The usefulness of rapid plateletpheresis in preventing additional morbidity in patients with thrombocytosis by removing large numbers of circulating platelets has already been documented. Moreover, during cardiopulmonary bypass, activation and aggregation of platelets and a series of biochemical reactions produce thrombin that may lead to thrombosis within the circuit causing interruption of extracorporeal circulation, vital organ malperfusion, and thromboembolic complications [6Grima K.M. Therapeutic apheresis in hematological and oncological diseases.J Clin Apheresis. 2000; 15: 28-52Crossref PubMed Scopus (56) Google Scholar, 7Taft E.G. Babcock R.B. Scharfman W.B. Tartaglia A.P. Plateletpheresis in the management of thrombocytosis.Blood. 1977; 50: 927-933PubMed Google Scholar]. In the present study, reduction of a significantly high platelet count to less than 400 × 103/μL in a thin-built (48 kg) elderly man with unstable blood pressure seemed to be challenging, particularly with an underlying severe coronary artery disease. For optimum patient safety, we performed all therapeutic platelet reduction procedures under continuous cardiac monitoring and prophylactic injectable calcium to avoid citrate toxicity. The draw rate and return rate of each cycle were limited to 50 mL per minute and 70 mL per minute, respectively, with a maximum extracorporeal blood volume of 246 mL. Studies regarding performance of various cell separators used for therapeutic reduction of platelets in ET is scarce in the medical literature. Although Taft and colleagues [7Taft E.G. Babcock R.B. Scharfman W.B. Tartaglia A.P. Plateletpheresis in the management of thrombocytosis.Blood. 1977; 50: 927-933PubMed Google Scholar] were able to collect 16 × 1011 to 26 × 1011 platelets, and up to 98 × 1011 when processing volumes of more than 10 L by using the Haemonetics model 10 (Haemonetics Corp, Braintree, MA) and the Aminco Celltrifuge (American Instrument Company, Santa Ana, CA), McCarthy and colleagues [8McCarthy L.J. Graves V.L. Eigen H. McGuire W.A. Platelet apheresis for extreme thrombocytosis in an 11-year-old girl with CML.Transfus Med. 1991; 1: 187-189Crossref PubMed Scopus (15) Google Scholar] found a reduction between 1,580 × 103/μL and 2,665 × 103/μL of peripheral platelets by apheresis when using the CS-3000 Fenwal separator. The present study found the Haemonetics MCS+ to be highly efficient in the acute management of ET, and as low as three procedures could significantly reduce the platelet count and prepare the patient for coronary artery bypass grafting. However, lack of clear guidelines and the presence of a nonfunctional platelet in ET posed a problem in establishing a safe preoperative baseline platelet count in our patient. We observed that a preoperative platelet count between 350 × 103/μL and 400 × 103/μL was safe, which could take care of the surgery, as well as the postsurgical platelet loss. Also, it is a controversial issue whether this reduction is adequate for long-term maintenance, because rebound phenomena is common in ET, and this was been observed in our patient a few days after surgery. The patient could be followed for the next 7 months during which he had 11 hospital visits and had maintained a platelet count of 247 × 103/μL to 301 × 103/μL with oral hydroxyurea (500 gm/day). In conclusion, therapeutic plateletpheresis is a useful measure in reducing platelet count rapidly in ET and relieving patients of acute symptoms. However, such procedures should be performed very meticulously in an ET patient who has severe underlying cardiac disorder and needs for urgent surgery.