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Detection of cold hemagglutination in a blood cardioplegia unit before systemic cooling of a patient with unsuspected cold agglutinin disease
CASE REPORTS
Detection of Cold Hemagglutination in a Blood Cardioplegia Unit Before Systemic Cooling of a Patient With Unsuspected Cold Agglutinin Disease Sue Boettcher Dake, BS, CCP, Marilyn F. M. Johnston, MD, PhD, Patricia Brueggeman, CCP, and Hendrick B. Barner, MD Departments of Surgery and Pathology, St. Louis University School of Medicine, St. Louis, Missouri
A case is described in which hemagglutination occurred intraoperatively in cold blood flushed through the blood cardioplegia delivery system from a patient with unsuspected cold agglutinin disease. On initiating cardiopulmonary bypass and then selectively cooling the perfusate in the blood cardioplegia delivery system before induc-
ing systemic cooling, it is possible to check for cold agglutination. Routine use of this technique may be worthwhile to detect cold agglutination in vitro before systemic cooling is begun in the rare patient with unsuspected cold agglutinins. (Ann Thorac Surg 1989;47:914-5)
H
agglutination. The specimen was tested directly with no refrigerator storage. Compatible units of blood were obtained and operation was planned using systemic hypothermia to 25°C with cold blood potassium cardioplegia infusion at 5" to 10°C. Cannulas were inserted and cardiopulmonary bypass instituted at 37°C. With the patient at normothermia, the cardioplegia unit (Electromedics D720 cardioplegic heat exchanger with 4: 1 bloodkrystalloid dilution tubing) was cooled with ice water from the heater-cooler (our normal procedure). The prime was flushed out and displaced with blood from the bypass circuit, and the effluent was collected. Distinct separation of red cells from the crystalloid-plasma mixture was noted. Cold agglutinin disease was suspected. Examination revealed red cell agglutination that reversed completely after warming to 37°C. To prevent potential harm to the microcirculation, bypass was maintained at normothermia and no cardioplegia was used. The heart was perfused and fibrillation induced electrically with subsequent discontinuation of the current. One left internal mammary artery graft and three distal reverse saphenous vein grafts were performed. A ten-minute cross-clamp period was used during one of four distal grafts. The other distal anastomoses were accomplished with local coronary occlusion. Because of the inability to cool the patient, the aortic valve was not inspected. This could complicate the procedure and expose the patient to the substantial risk of normothermic ischemia to decalcify a valve with a minimal gradient. After 91 minutes of fibrillation, the heart was defibrillated once at 10 J and allowed to beat while the two proximal anastomoses were made. The patient was weaned from bypass after a total of two hours 16 minutes. Subsequent patient evaluation revealed no viral infection, malignancy, or autoimmune disorder. A cold agglutinin titer of 1:2,048 at 1" to 5°C (Fig 1) and a microscopically positive direct antiglobulin test due to complement only are consistent with idiopathic cold agglutinins. The
ypothermic cardiopulmonary bypass carries the risk-however remote-of red cell agglutination caused by unsuspected cold agglutinin disease. Today's efficient blood cardioplegia systems that deliver sanguinous solutions at 5" to 10°C may precipitate cold agglutination in the rare patient with this disease. If cold agglutinin disease is recognized before operation, alternatives such as preoperative plasma exchange [l]or use of warm crystalloid cardioplegia to displace the blood in the heart before cardioplegic cooling [2, 31 are available. Alternatively, operation may be conducted at normothermia. These methods assume the problem is recognized before cooling is begun. However, pretransfusion testing is not designed to identify cold agglutinins, particularly those of low thermal amplitude. As cold agglutinin disease is frequently asymptomatic, patients could come to operation with unsuspected disease. Obviously it is desirable to recognize the problem before agglutination occurs in vivo. A case is described in which hemagglutination was observed intraoperatively, but before systemic cooling, in cold blood flushed from the cold blood cardioplegia unit. This discovery allowed avoidance of systemic hypothermia and cold blood cardioplegia. A 65-year-old man with triple-vessel coronary artery disease and a 16-mm Hg peak systolic gradient across his aortic valve was scheduled for coronary artery bypass grafting and aortic valve decalcification. The left ventricle was moderately hypokinetic. Pretransfusion testing microscopically identified a cold alloantibody with M specificity; a positive direct antiglobulin test due to complement only and no spontaneous Accepted for publication Nov 28, 1988. Address reprint requests to Dr Johnston, Department of Pathology, St. Louis University School of Medicine, 1325 South Grand Blvd, St. Louis, MO 63104.
0 1989 by The Society of Thoracic Surgeons
0003-4975/89/$3.50
Ann Thorac Surg 1989:479145
Fig 1 . Cold henragglutination of patient's whole blood in vitro.
postoperative course was free of cardiac complications. Serial tests of the MB isoenzymes of creatine kinase did not reveal perioperative myocardial infarction (peak value, 26 IU/L) and serial electrocardiograms had no new Q-wave.
Comment Cold agglutinin disease, an autoimmune phenomenon in which antibody directly agglutinates red cells at temperatures below body temperature and maximally at 0" to 5"C, is most frequently asymptomatic but may cause hemolytic anemia or peripheral vessel occlusive phenomenon, usually initiated by cold exposure. The disease may be associated with infection or with lymphoproliferative or autoimmune disorders [4]. The idiopathic form has a peak incidence after age 50 years, a usual age for cardiac bypass procedures. Thermal amplitude of cold agglutinins, the highest
DAKEETAL COLD HEMAGGLUTININS AND CARDIOPLEGIA
915
temperature at which agglutination occurs, is rarely more than 30°C and usually less than 25"C, particularly in the asymptomatic patient. Pretransfusion testing performed on freshly obtained specimens occurs at room temperature at the lowest and can miss agglutination when the thermal amplitude is less than room temperature. Therefore, cold agglutinins of low thermal amplitude can be missed in pretransfusion testing using recently drawn specimens with no refrigerator storage. On the other hand, many "cold" reacting antibodies observed at room temperature during routine pretransfusion testing do not cause direct spontaneous agglutination or hemolysis of red cells in vivo and are routinely considered not to be clinically significant even in patients undergoing hypothermia. Because cold agglutinin disease is rare, testing for this phenomenon is not usually done. It is clear that our technique allowed us to recognize agglutination in the cardioplegia unit and prevent possible massive agglutination. Once discovered, the problem was circumvented by a normothermic method of myocardial protection. We believe this technique of cooling the cardioplegia unit alone first will help detect cold agglutinins in vitro before systemic cooling in the rare patient with unsuspected cold agglutinin disease.
References 1. Klein HG, Faltz LL, McIntosh CL, et al. Surgical hypothermia in a patient with a cold agglutinin: management by plasma exchange. Transfusion 1980;20:354-7. 2. Berreklouw E, Moulijn AC, Pegels JG, Meijne NC. Myocardial protection with cold cardioplegia in a patient with cold autoagglutinins and hemolysins. Ann Thorac Surg 1982;33:521-2. 3. Blumberg N, Hicks G, Woll J, et al. Successful cardiac bypass surgery in the presence of a potent cold agglutinin without plasma exchange. Transfusion 1983;23:363. 4. Diaz JH, Cooper ES, Ochsner JL. Cold hemagglutination pathophysiology: evaluation and management of patients undergoing cardiac surgery with induced hypothermia. Arch Intern Med 1984;144:1639-41.
Detection of Cold Hemagglutination in a Blood Cardioplegia Unit Before Systemic Cooling of a Patient With Unsuspected Cold Agglutinin Disease Sue Boettcher Dake, BS, CCP, Marilyn F. M. Johnston, MD, PhD, Patricia Brueggeman, CCP, and Hendrick B. Barner, MD Departments of Surgery and Pathology, St. Louis University School of Medicine, St. Louis, Missouri
A case is described in which hemagglutination occurred intraoperatively in cold blood flushed through the blood cardioplegia delivery system from a patient with unsuspected cold agglutinin disease. On initiating cardiopulmonary bypass and then selectively cooling the perfusate in the blood cardioplegia delivery system before induc-
ing systemic cooling, it is possible to check for cold agglutination. Routine use of this technique may be worthwhile to detect cold agglutination in vitro before systemic cooling is begun in the rare patient with unsuspected cold agglutinins. (Ann Thorac Surg 1989;47:914-5)
H
agglutination. The specimen was tested directly with no refrigerator storage. Compatible units of blood were obtained and operation was planned using systemic hypothermia to 25°C with cold blood potassium cardioplegia infusion at 5" to 10°C. Cannulas were inserted and cardiopulmonary bypass instituted at 37°C. With the patient at normothermia, the cardioplegia unit (Electromedics D720 cardioplegic heat exchanger with 4: 1 bloodkrystalloid dilution tubing) was cooled with ice water from the heater-cooler (our normal procedure). The prime was flushed out and displaced with blood from the bypass circuit, and the effluent was collected. Distinct separation of red cells from the crystalloid-plasma mixture was noted. Cold agglutinin disease was suspected. Examination revealed red cell agglutination that reversed completely after warming to 37°C. To prevent potential harm to the microcirculation, bypass was maintained at normothermia and no cardioplegia was used. The heart was perfused and fibrillation induced electrically with subsequent discontinuation of the current. One left internal mammary artery graft and three distal reverse saphenous vein grafts were performed. A ten-minute cross-clamp period was used during one of four distal grafts. The other distal anastomoses were accomplished with local coronary occlusion. Because of the inability to cool the patient, the aortic valve was not inspected. This could complicate the procedure and expose the patient to the substantial risk of normothermic ischemia to decalcify a valve with a minimal gradient. After 91 minutes of fibrillation, the heart was defibrillated once at 10 J and allowed to beat while the two proximal anastomoses were made. The patient was weaned from bypass after a total of two hours 16 minutes. Subsequent patient evaluation revealed no viral infection, malignancy, or autoimmune disorder. A cold agglutinin titer of 1:2,048 at 1" to 5°C (Fig 1) and a microscopically positive direct antiglobulin test due to complement only are consistent with idiopathic cold agglutinins. The
ypothermic cardiopulmonary bypass carries the risk-however remote-of red cell agglutination caused by unsuspected cold agglutinin disease. Today's efficient blood cardioplegia systems that deliver sanguinous solutions at 5" to 10°C may precipitate cold agglutination in the rare patient with this disease. If cold agglutinin disease is recognized before operation, alternatives such as preoperative plasma exchange [l]or use of warm crystalloid cardioplegia to displace the blood in the heart before cardioplegic cooling [2, 31 are available. Alternatively, operation may be conducted at normothermia. These methods assume the problem is recognized before cooling is begun. However, pretransfusion testing is not designed to identify cold agglutinins, particularly those of low thermal amplitude. As cold agglutinin disease is frequently asymptomatic, patients could come to operation with unsuspected disease. Obviously it is desirable to recognize the problem before agglutination occurs in vivo. A case is described in which hemagglutination was observed intraoperatively, but before systemic cooling, in cold blood flushed from the cold blood cardioplegia unit. This discovery allowed avoidance of systemic hypothermia and cold blood cardioplegia. A 65-year-old man with triple-vessel coronary artery disease and a 16-mm Hg peak systolic gradient across his aortic valve was scheduled for coronary artery bypass grafting and aortic valve decalcification. The left ventricle was moderately hypokinetic. Pretransfusion testing microscopically identified a cold alloantibody with M specificity; a positive direct antiglobulin test due to complement only and no spontaneous Accepted for publication Nov 28, 1988. Address reprint requests to Dr Johnston, Department of Pathology, St. Louis University School of Medicine, 1325 South Grand Blvd, St. Louis, MO 63104.
0 1989 by The Society of Thoracic Surgeons
0003-4975/89/$3.50
Ann Thorac Surg 1989:479145
Fig 1 . Cold henragglutination of patient's whole blood in vitro.
postoperative course was free of cardiac complications. Serial tests of the MB isoenzymes of creatine kinase did not reveal perioperative myocardial infarction (peak value, 26 IU/L) and serial electrocardiograms had no new Q-wave.
Comment Cold agglutinin disease, an autoimmune phenomenon in which antibody directly agglutinates red cells at temperatures below body temperature and maximally at 0" to 5"C, is most frequently asymptomatic but may cause hemolytic anemia or peripheral vessel occlusive phenomenon, usually initiated by cold exposure. The disease may be associated with infection or with lymphoproliferative or autoimmune disorders [4]. The idiopathic form has a peak incidence after age 50 years, a usual age for cardiac bypass procedures. Thermal amplitude of cold agglutinins, the highest
DAKEETAL COLD HEMAGGLUTININS AND CARDIOPLEGIA
915
temperature at which agglutination occurs, is rarely more than 30°C and usually less than 25"C, particularly in the asymptomatic patient. Pretransfusion testing performed on freshly obtained specimens occurs at room temperature at the lowest and can miss agglutination when the thermal amplitude is less than room temperature. Therefore, cold agglutinins of low thermal amplitude can be missed in pretransfusion testing using recently drawn specimens with no refrigerator storage. On the other hand, many "cold" reacting antibodies observed at room temperature during routine pretransfusion testing do not cause direct spontaneous agglutination or hemolysis of red cells in vivo and are routinely considered not to be clinically significant even in patients undergoing hypothermia. Because cold agglutinin disease is rare, testing for this phenomenon is not usually done. It is clear that our technique allowed us to recognize agglutination in the cardioplegia unit and prevent possible massive agglutination. Once discovered, the problem was circumvented by a normothermic method of myocardial protection. We believe this technique of cooling the cardioplegia unit alone first will help detect cold agglutinins in vitro before systemic cooling in the rare patient with unsuspected cold agglutinin disease.
References 1. Klein HG, Faltz LL, McIntosh CL, et al. Surgical hypothermia in a patient with a cold agglutinin: management by plasma exchange. Transfusion 1980;20:354-7. 2. Berreklouw E, Moulijn AC, Pegels JG, Meijne NC. Myocardial protection with cold cardioplegia in a patient with cold autoagglutinins and hemolysins. Ann Thorac Surg 1982;33:521-2. 3. Blumberg N, Hicks G, Woll J, et al. Successful cardiac bypass surgery in the presence of a potent cold agglutinin without plasma exchange. Transfusion 1983;23:363. 4. Diaz JH, Cooper ES, Ochsner JL. Cold hemagglutination pathophysiology: evaluation and management of patients undergoing cardiac surgery with induced hypothermia. Arch Intern Med 1984;144:1639-41.