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Heart Surgery in Infants With Hemophilia
336
CASE REPORT MURUGAN ET AL HEART SURGERY IN INFANTS WITH HEMOPHILIA
Ann Thorac Surg 2006;81:336 –9
Fig 3. This dagger-shaped glass shard was removed from the heart.
FEATURE ARTICLES
Fig 1. The scar of the neck. The arrow shows the location of the scar.
that echocardiography could detect glass. The signal intensity was similar to a rib. From this experience, we speculate that computed tomography or magnetic resonance imaging may be more accurate for the diagnosis of nonmetal foreign bodies in the heart. It was a miracle that the patient survived the glass wound to her right ventricle and initially recovered after 10 days of conservative management. We deduce that two factors helped the patient. First, the right ventricle was a low-pressure chamber. Second, the glass pene-
trated the heart, pericardium, and the right pleura at the same time, and intrapericardial fluid drained into the right pleural cavity in time to prevent severe acute cardiac tamponade. Admitting our limited experience in treating chronic cardiac foreign bodies, we chose to remove the glass by a skin incision and repair the right ventricular wound through sternotomy during cardiopulmonary bypass. We found firm pericardial adhesions that allowed direct removal of the glass shard through a separate skin incision without producing acute pericardial temponade. The authors thank Dr Weiguo Ma for reviewing the manuscript.
Reference 1. Actis Dato GM, Arslanian A, Marzio PD, Filosso PL, Ruffini E. Posttraumatic and iatrogenic foreign bodies in the heart: report of fourteen cases and review of the literature. J Thorac Cardiovasc Surg 2003;126:408 –14.
Heart Surgery in Infants With Hemophilia Subramanian Jothi Murugan, MRCP, Sangeetha Viswanathan, MRCPCH, John Thomson, MRCP, Jonathan M. Parsons, FRCP, and Mike Richards, DM, MRCP Departments of Pediatric Cardiology and Hematology, Leeds General Infirmary, Leeds, United Kingdom
We describe 2 infants with hemophilia A who had heart surgery under cardiopulmonary bypass with factor VIII replacement therapy, and we recommend a guideline for Accepted for publication Sept 1, 2004.
Fig 2. Computed tomography image reveals a foreign body in the right ventricle and right thorax. © 2006 by The Society of Thoracic Surgeons Published by Elsevier Inc
Address correspondence to Dr Murugan, Non-Invasive Unit, Department of Pediatric Cardiology, E Floor, Jubilee Building, Leeds General Infirmary, Great George St, Leeds, LS1 3EX UK; e-mail: jothidevi1@ hotmail.com.
0003-4975/06/$32.00 doi:10.1016/j.athoracsur.2004.09.001
Ann Thorac Surg 2006;81:336 –9
CASE REPORT MURUGAN ET AL HEART SURGERY IN INFANTS WITH HEMOPHILIA
C
ardiac surgery in infants with hemophilia can be a difficult problem, as significant coagulation abnormalities may occur during and after surgery. Careful preoperative planning and meticulous postoperative monitoring of factor VIII replacement therapy are essential in maintaining optimal hemostasis. Although considerable advances have been made in the management of hemophilia, there is a lack of guidelines pertaining to cardiac surgery in children. This report illustrates our successful experience of managing 2 infants, and we recommend our guidelines for cardiac surgery in children with hemophilia.
Case Reports Patient 1 A 5-week-old infant presented with breathlessness and cyanosis. An echocardiogram showed total anomalous pulmonary venous connection. His mother and grandmother were known carriers for hemophilia A. Soon after a difficult delivery, factor VIII level was low (11 IU/dL vs normal values 50 to 150 IU/dL), and therefore he was given a prophylactic dose of 35 IU/kg of Kogenate-Bayer (Bayer plc, UK) factor VIII concentrate. At the time of referral to the cardiac team, the patient’s factor VIII level was 19 IU/dL. Preoperative detailed written plans were made to monitor and replace factor VIII during and after surgery. We aimed for factor VIII level greater than 100 IU/dL before surgery. Two reliable venous cannulas were inserted; one for administration of factor VIII and another for blood sampling. Close vigilance for the patency of the intravenous cannula was maintained. Repair of total anomalous pulmonary venous connection was performed with a cardiopulmonary
bypass time of 89 minutes and an aortic cross-clamp time of 37 minutes. Throughout surgery, including bypass and heparinization, a continuous infusion of Kogenate-Bayer (Bayer) factor VIII concentrate was maintained. Monitoring of factor VIII levels and replacement were done (Table 1). Postoperatively factor VIII levels were monitored twice daily and the infusion rate was adjusted accordingly with the aim of keeping blood levels between 50 to 100 IU/dL. The infusion was discontinued on postoperative day 8 (139 IU/dL) and two further boluses of 250 IU/dL factor VIII were given on alternate days. There were no hemorrhagic events, and the patient made an excellent recovery.
Patient 2 This infant, who already had a ventricular septal defect, presented with heart failure at 11 weeks of age. He was noted to have a large right atrium raising concerns of anomalous pulmonary venous drainage. As echocardiography was inconclusive, cardiac catheterization was planned. His mother and maternal grandmother were hemophilia A carriers, as were her 3 sisters who had several affected offspring. Therefore, his factor VIII level was checked and found to be low at 5 IU/dL (5%). Before cardiac catheterization, he received a bolus of ReFacto (Wyeth Laboratories, UK) factor VIII concentrate with levels being checked. The level obtained was well above the target level of 50 IU/dL and the procedure was carried out without any complications. A diagnosis of total anomalous pulmonary venous connection with a ventricular septal defect was confirmed and a decision was made to repair the defects by surgery. A detailed plan was made to manage his Factor VIII replacement intra and postoperatively using a continuous infusion of ReFacto (Wyeth Laboratories) along similar lines to patient 1 (Table 2). Surgery was uneventful and he made an uncomplicated recovery. The factor VIII infusion was discontinued on postoperative day 11.
Comment Both infants with congenital heart disease were investigated for hemophilia in view of a strong family history. We made detailed plans for preoperative, perioperative, and postoperative management. The infants made an
Table 1. Management Plan for Cardiac Surgery on Infant 1a Time Three hours prior to surgery One hour prior to surgery During surgery After reversal of heparinization (90 min from onset of bypass) 6 hr after bypass 12 hr after bypass a
Weight, 3.6 kg.
Factor VIII Level (IU/dL)
Dose of Intravenous Factor VIII Concentrate (IU)
11.4 167 147 60
Bolus 250 units, followed by infusion of 40 units/hr Infusion 40 units/hr Infusion 40 units/hr 250 units as bolus, infusion increased 50 units/hr
148 266
50 units/hr 50 units/hr
FEATURE ARTICLES
factor VIII support for cardiac surgery. One child had repair of total anomalous pulmonary venous connection. The second had cardiac catheterization followed by repair of ventricular septal defect and total anomalous pulmonary venous connection. Close collaboration between hematologist, laboratory, cardiologist, and cardiac surgeon is crucial in successful management of coagulation abnormalities during and after surgery. (Ann Thorac Surg 2006;81:336 –9) © 2006 by The Society of Thoracic Surgeons
337
338
CASE REPORT MURUGAN ET AL HEART SURGERY IN INFANTS WITH HEMOPHILIA
Table 2. Management Plan for Cardiac Surgery on Infant 2a
Time
Factor VIII Level (IU/dL)
Dose of Intravenous Factor VIII Concentrate (IU)
Three hours prior to surgery
6
One hour prior to surgery During surgery After reversal of heparinization 6 hr after bypass
195
Bolus of 500 units followed by infusion at 50 units/hr Infusion 50 units/hr
222 102
Infusion 50 units/hr Infusion 50 units/hr
12 hr after bypass
99
a
91
500 units as bolus, infusion increased 62.5 units/hr Infusion 62.5 units/hr
Weight, 4.5 kg.
FEATURE ARTICLES
excellent recovery without complications related to factor VIII deficiency. On the basis of our successful management, we include a guideline for the management of factor VIII deficiency during cardiac surgery (Table 3). Our success must be attributed to cooperation with cardiac surgeons, cardiologists, hematologists, anesthesiologists, blood bank, perfusionists, and the coagulation laboratory. Although cardiac surgery and catheterization in adults with hemophilia has been reported in literature, only few reports are available on children [1– 4], and none have been reported on infants. Replacement with the missing coagulation factor is the mainstay of treatment. Although the initial procedures involved intermittent bolus therapy, recently factor VIII concentrates have been successfully administered by continuous intravenous infusion [5]. The use of continuous infusion of factor VIII is not currently licensed by the manufacturers. However, continuous infusion provided a steady state plasma concentration of factor VIII during cardiac bypass and also allowed for manipulation of factor VIII administration without the need for separate boluses of concentrate. These advantages were significant because the cardiothoracic unit was based at a hospital distant from the hemophilia center. The measurement of the plasma factor VIII concentration during bypass was performed by a chromogenic method because a coagulation based assay would have been invalidated by the concurrent use of heparin. The postoperative regime of bolus versus continuous infusion was decided on pragmatic terms considering nursing expertise, stability of the factor VIII product, and venous access. It is the practice of the supervising hemophilia center to use a variety of recombinant factor VIII products to safeguard from supply shortages. Each individual patient will remain on the initially allocated product. The assay of Refacto (Wyeth Laboratories) does require use of a specific concentrate plasma standard, but the efficacy in establishing hemostasis is not significantly different from other factor VIII products.
Ann Thorac Surg 2006;81:336 –9
There is a concern that exposure of hemophilia patients to factor VIII at an early age may increase the risk of factor VIII inhibitor development [6]. Factor VIII inhibitors are antibodies that bind to exogenously administered factor VIII reducing or abolishing its efficacy. In cases of mild or moderate hemophilia A, these inhibitors may also bind to endogenous factor VIII, thus increasing the severity of the bleeding disorder. Both patients described had mild or moderate hemophilia A, neither had evidence for an inhibitor before surgery, and no inhibitor is evident in either patient after 17 and 24 months of follow-up, respectively. However, there is a need for ongoing inhibitor surveillance. The use of recombinant factor VIIa has been suggested as an alternative to factor VIII to avoid inhibitor development [7]. Leggett and colleagues [8] described a successful cardiac operation in a young boy with severe factor VIII deficiency with high titer of antibodies. Both of our infants had not received multiple transfusions before surgery and were negative for antibodies. The therapeutic regime to establish hemostasis in other coagulation factor deficiencies will depend on the nature and severity of the factor deficiency. Factor concentrates are available for deficiencies of all coagulation factors other than factor V. Concentrates may be prepared by recombinant DNA technology and be free of plasma; other products are prepared by plasma fraction-
Table 3. Guideline for Factor VIII Replacement Therapy in Cardiac Surgery Preoperatively Check factor VIII inhibitor levels preoperatively. Check baseline clotting and factor VIII levels. Establish reliable venous access—one for sampling and the other for administration of factor VIII. On the day of surgery Bolus of factor VIII to achieve factor VIII level of 100 IU/dL administered for 5 minutes, 2 to 3 hours prior to surgery. Then start continuous infusion of factor VIII at a rate of 10 ⫻ weight/hr (IU/hr)a—piggyback a normal saline infusion of about 10 mL/hr to alert staff to cannula tissuing. Check factor VIII level 1 hour later (target ⬎ 100 IU/dL prior to surgery) Repeat level preheparinization—give bolus if required (target ⬎ 100 IU/dL) and increase infusion rate. Repeat level 30 minutes into bypass—patient will need chromogenic factor VIII/heparin neutralization in the laboratory. Postoperatively Repeat levels at 4 to 6 hour intervals in the immediate postoperative period and titrate the infusion accordingly. Continue the infusion for 7 to 14 days postoperatively (checking factor VIII levels twice daily during the first 3 postoperative days and less frequently thereafter). Introduce bolus doses when factor VIII levels are predictable according to local practice. a Infusion rate (U/kg/hr) ⫽ desired plasma level (IU/mL) ⫻ clearance (mL/kg/hr). Initial estimated clearance ⫽ 10 mL/kg/hr. Desired plasma level ⫽ 1 IU/mL (⫽ 10 IU/dL or 100%). Initial infusion rate ⫽ 10 ⫻ wt/hr ⫽ 40 IU/hr.
Ann Thorac Surg 2006;81:339 – 41
References 1. MacKinlay N, Taper J, Renisson F, Richard K. Cardiac surgery and catheterisation in patients with haemophilia. Haemophilia 2000;6(2):84 – 8. 2. Nomura K, Nakumara Y, Yamagishi M, Yamamoto K, Hanada R. Perioperative management of ventricular septal defect and right coronary cusp prolapse in a patient with haemophilia A. Kyobu Geka (Japanese) 1994;47(13):1071– 4. 3. Nakajima H, Takada K, Taguchi A, et al. Anaesthetic management of hemophilia A carrier for palliative operation and radical repair of a cardiac anomaly. Maui-Japanese J Anesth 1992;41(3):460 –3. 4. Boilletot A, De Geeter B, Wiesel ML, et al. Surgical correction of interventricular communication with pulmonary stenosis in a haemophiliac. Arch Fr Pediatr 1983;40(7):571–3. 5. Rochat C, McFayden ML, Schwyzer R, Gillham A, Cruickshank A. Continuous infusion of intermediate – purity factor VIII in haemophilia patients undergoing elective surgery. Haemophilia 1995;5:181– 6. 6. Van der Bom JG, Mauser-Bunschoten EP, Fischer K, van den Berg HM. Age at first treatment and immune tolerance to factor VIII in severe hemophilia. Thromb Haemost 2003;89(3): 475–9. 7. Major surgery in haemophiliac patients with inhibitors using recombinant factor VIIa. Haemostasis 1996;26(Suppl 1):118 –23. 8. Leggett PL, Doyle D, Smith WB, et al. Elective cardiac operation in a patient with severe hemophilia and acquired factor VIII antibodies. J Thorac Cardiovasc Surg 1984;87(4):556 – 60. © 2006 by The Society of Thoracic Surgeons Published by Elsevier Inc
339
Infectious Ductal Aneurysm After Coil Embolization in an Infant Takeshi Shinkawa, MD, Masaaki Yamagishi, MD, Keisuke Shuntoh, MD, Katsuji Fujiwara, MD, Taiji Watanabe, MD, and Satomi Yoshida, MD Department of Pediatric Cardiovascular Surgery, Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
We report a case of ductal aneurysm after transcatheter coil embolization in an infant. The aneurysm was asymptomatic and was not detected until it ruptured during surgical intervention. We suspect that the aneurysm was induced by methicillin-resistant Staphylococcus aureus infection, as the resected aneurysmal wall was severely infiltrated by inflammatory cells and the patient had recurrent methicillin-resistant Staphylococcus aureus infection. We recommend remaining on guard against formation of a ductal aneurysm after coil embolization, especially in patients with associated recurrent bacteremia. (Ann Thorac Surg 2006;81:339 – 41) © 2006 by The Society of Thoracic Surgeons
T
ranscatheter coil embolization of the patent ductus arteriosus is widely used to treat patients with patent ductus arteriosus and pulmonary hypertension. We describe a 9-month-old girl who developed a ductal aneurysm after coil embolization. One week after birth, a girl with situs inversus, doubleoutlet right ventricle, large remote type ventricular septal defect, transposition of the great arteries, infundibular pulmonary stenosis, patent ductus arteriosus, and pulmonary hypertension developed necrotizing enterocolitis. She was treated with imipenem with immediate improvement in her inflammation, but a barium enema examination performed at 1 month of age showed severe stenosis of the sigmoid colon. At the age of 2 months, she was referred to our hospital. She had septic shock caused by methicillin-resistant Staphylococcus aureus (MRSA) and was treated with vancomycin and exchange transfusions. At the age of 3 months, she underwent resection of the stenotic colon and creation of a stoma. Frequent recurring respiratory infections and uncontrollable heart failure persisted, leading to a cardiac catheter examination, which was performed at 5 months of age and which revealed pulmonary hypertension with high pulmonary blood flow. To decrease pulmonary blood flow, we embolized the patent ductus arteriosus using a detachable coil with three 5-mm loops (Flipper, Cook, IN) at the age of 7 months (Fig 1). The patient’s general condition did Accepted for publication Sept 24, 2004. Address correspondence to Dr Shinkawa, Department of Pediatric Cardiovascular Surgery, Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kawaramachi, Hirokoji, Kamigyo-ku, Kyoto 602– 8566, Japan; e-mail: [email protected].
0003-4975/06/$32.00 doi:10.1016/j.athoracsur.2004.09.049
FEATURE ARTICLES
ation techniques. In principle, the use of plasma derived products should be avoided if a safe alternative is available. Desmopressin (1-desamino-8-D-arginine vasopressin) is a synthetic analogue of vasopressin and is used in cases of mild or moderate hemophilia A and certain subsets of von Willebrand’s disease. Use of this drug in appropriate patients results in the elevation of circulating plasma levels of factor VIII and von Willebrand factor sufficient enough to establish hemostasis. However, the use of this drug in neonates should be avoided because of the risk of hyponatremia; furthermore the efficacy of this approach would be questionable in cases of lifethreatening surgery requiring prolonged normalization of coagulation factor levels. Therefore, in practice, management of cases of cardiac surgery in neonates with hemophilia will require replacement with appropriate factor concentrate. A generic regime for all other bleeding disorders will be impractical given the varied half lives and hemostatic levels for other coagulation factors. In conclusion, children with hemophilia present an increased challenge to the cardiac surgical team. These two examples illustrate that cardiac operations using systemic heparinization can be safely performed in infants with hemophilia when carried out with preoperative and perioperative support from the hematology service, adequate replacement therapy using blood components, and careful monitoring of the coagulation status. Our guideline for factor VIII replacement therapy during and after cardiac surgery may be appropriate for other centers.
CASE REPORT SHINKAWA ET AL INFECTIOUS DUCTAL ANEURYSM AFTER COILING
CASE REPORT MURUGAN ET AL HEART SURGERY IN INFANTS WITH HEMOPHILIA
Ann Thorac Surg 2006;81:336 –9
Fig 3. This dagger-shaped glass shard was removed from the heart.
FEATURE ARTICLES
Fig 1. The scar of the neck. The arrow shows the location of the scar.
that echocardiography could detect glass. The signal intensity was similar to a rib. From this experience, we speculate that computed tomography or magnetic resonance imaging may be more accurate for the diagnosis of nonmetal foreign bodies in the heart. It was a miracle that the patient survived the glass wound to her right ventricle and initially recovered after 10 days of conservative management. We deduce that two factors helped the patient. First, the right ventricle was a low-pressure chamber. Second, the glass pene-
trated the heart, pericardium, and the right pleura at the same time, and intrapericardial fluid drained into the right pleural cavity in time to prevent severe acute cardiac tamponade. Admitting our limited experience in treating chronic cardiac foreign bodies, we chose to remove the glass by a skin incision and repair the right ventricular wound through sternotomy during cardiopulmonary bypass. We found firm pericardial adhesions that allowed direct removal of the glass shard through a separate skin incision without producing acute pericardial temponade. The authors thank Dr Weiguo Ma for reviewing the manuscript.
Reference 1. Actis Dato GM, Arslanian A, Marzio PD, Filosso PL, Ruffini E. Posttraumatic and iatrogenic foreign bodies in the heart: report of fourteen cases and review of the literature. J Thorac Cardiovasc Surg 2003;126:408 –14.
Heart Surgery in Infants With Hemophilia Subramanian Jothi Murugan, MRCP, Sangeetha Viswanathan, MRCPCH, John Thomson, MRCP, Jonathan M. Parsons, FRCP, and Mike Richards, DM, MRCP Departments of Pediatric Cardiology and Hematology, Leeds General Infirmary, Leeds, United Kingdom
We describe 2 infants with hemophilia A who had heart surgery under cardiopulmonary bypass with factor VIII replacement therapy, and we recommend a guideline for Accepted for publication Sept 1, 2004.
Fig 2. Computed tomography image reveals a foreign body in the right ventricle and right thorax. © 2006 by The Society of Thoracic Surgeons Published by Elsevier Inc
Address correspondence to Dr Murugan, Non-Invasive Unit, Department of Pediatric Cardiology, E Floor, Jubilee Building, Leeds General Infirmary, Great George St, Leeds, LS1 3EX UK; e-mail: jothidevi1@ hotmail.com.
0003-4975/06/$32.00 doi:10.1016/j.athoracsur.2004.09.001
Ann Thorac Surg 2006;81:336 –9
CASE REPORT MURUGAN ET AL HEART SURGERY IN INFANTS WITH HEMOPHILIA
C
ardiac surgery in infants with hemophilia can be a difficult problem, as significant coagulation abnormalities may occur during and after surgery. Careful preoperative planning and meticulous postoperative monitoring of factor VIII replacement therapy are essential in maintaining optimal hemostasis. Although considerable advances have been made in the management of hemophilia, there is a lack of guidelines pertaining to cardiac surgery in children. This report illustrates our successful experience of managing 2 infants, and we recommend our guidelines for cardiac surgery in children with hemophilia.
Case Reports Patient 1 A 5-week-old infant presented with breathlessness and cyanosis. An echocardiogram showed total anomalous pulmonary venous connection. His mother and grandmother were known carriers for hemophilia A. Soon after a difficult delivery, factor VIII level was low (11 IU/dL vs normal values 50 to 150 IU/dL), and therefore he was given a prophylactic dose of 35 IU/kg of Kogenate-Bayer (Bayer plc, UK) factor VIII concentrate. At the time of referral to the cardiac team, the patient’s factor VIII level was 19 IU/dL. Preoperative detailed written plans were made to monitor and replace factor VIII during and after surgery. We aimed for factor VIII level greater than 100 IU/dL before surgery. Two reliable venous cannulas were inserted; one for administration of factor VIII and another for blood sampling. Close vigilance for the patency of the intravenous cannula was maintained. Repair of total anomalous pulmonary venous connection was performed with a cardiopulmonary
bypass time of 89 minutes and an aortic cross-clamp time of 37 minutes. Throughout surgery, including bypass and heparinization, a continuous infusion of Kogenate-Bayer (Bayer) factor VIII concentrate was maintained. Monitoring of factor VIII levels and replacement were done (Table 1). Postoperatively factor VIII levels were monitored twice daily and the infusion rate was adjusted accordingly with the aim of keeping blood levels between 50 to 100 IU/dL. The infusion was discontinued on postoperative day 8 (139 IU/dL) and two further boluses of 250 IU/dL factor VIII were given on alternate days. There were no hemorrhagic events, and the patient made an excellent recovery.
Patient 2 This infant, who already had a ventricular septal defect, presented with heart failure at 11 weeks of age. He was noted to have a large right atrium raising concerns of anomalous pulmonary venous drainage. As echocardiography was inconclusive, cardiac catheterization was planned. His mother and maternal grandmother were hemophilia A carriers, as were her 3 sisters who had several affected offspring. Therefore, his factor VIII level was checked and found to be low at 5 IU/dL (5%). Before cardiac catheterization, he received a bolus of ReFacto (Wyeth Laboratories, UK) factor VIII concentrate with levels being checked. The level obtained was well above the target level of 50 IU/dL and the procedure was carried out without any complications. A diagnosis of total anomalous pulmonary venous connection with a ventricular septal defect was confirmed and a decision was made to repair the defects by surgery. A detailed plan was made to manage his Factor VIII replacement intra and postoperatively using a continuous infusion of ReFacto (Wyeth Laboratories) along similar lines to patient 1 (Table 2). Surgery was uneventful and he made an uncomplicated recovery. The factor VIII infusion was discontinued on postoperative day 11.
Comment Both infants with congenital heart disease were investigated for hemophilia in view of a strong family history. We made detailed plans for preoperative, perioperative, and postoperative management. The infants made an
Table 1. Management Plan for Cardiac Surgery on Infant 1a Time Three hours prior to surgery One hour prior to surgery During surgery After reversal of heparinization (90 min from onset of bypass) 6 hr after bypass 12 hr after bypass a
Weight, 3.6 kg.
Factor VIII Level (IU/dL)
Dose of Intravenous Factor VIII Concentrate (IU)
11.4 167 147 60
Bolus 250 units, followed by infusion of 40 units/hr Infusion 40 units/hr Infusion 40 units/hr 250 units as bolus, infusion increased 50 units/hr
148 266
50 units/hr 50 units/hr
FEATURE ARTICLES
factor VIII support for cardiac surgery. One child had repair of total anomalous pulmonary venous connection. The second had cardiac catheterization followed by repair of ventricular septal defect and total anomalous pulmonary venous connection. Close collaboration between hematologist, laboratory, cardiologist, and cardiac surgeon is crucial in successful management of coagulation abnormalities during and after surgery. (Ann Thorac Surg 2006;81:336 –9) © 2006 by The Society of Thoracic Surgeons
337
338
CASE REPORT MURUGAN ET AL HEART SURGERY IN INFANTS WITH HEMOPHILIA
Table 2. Management Plan for Cardiac Surgery on Infant 2a
Time
Factor VIII Level (IU/dL)
Dose of Intravenous Factor VIII Concentrate (IU)
Three hours prior to surgery
6
One hour prior to surgery During surgery After reversal of heparinization 6 hr after bypass
195
Bolus of 500 units followed by infusion at 50 units/hr Infusion 50 units/hr
222 102
Infusion 50 units/hr Infusion 50 units/hr
12 hr after bypass
99
a
91
500 units as bolus, infusion increased 62.5 units/hr Infusion 62.5 units/hr
Weight, 4.5 kg.
FEATURE ARTICLES
excellent recovery without complications related to factor VIII deficiency. On the basis of our successful management, we include a guideline for the management of factor VIII deficiency during cardiac surgery (Table 3). Our success must be attributed to cooperation with cardiac surgeons, cardiologists, hematologists, anesthesiologists, blood bank, perfusionists, and the coagulation laboratory. Although cardiac surgery and catheterization in adults with hemophilia has been reported in literature, only few reports are available on children [1– 4], and none have been reported on infants. Replacement with the missing coagulation factor is the mainstay of treatment. Although the initial procedures involved intermittent bolus therapy, recently factor VIII concentrates have been successfully administered by continuous intravenous infusion [5]. The use of continuous infusion of factor VIII is not currently licensed by the manufacturers. However, continuous infusion provided a steady state plasma concentration of factor VIII during cardiac bypass and also allowed for manipulation of factor VIII administration without the need for separate boluses of concentrate. These advantages were significant because the cardiothoracic unit was based at a hospital distant from the hemophilia center. The measurement of the plasma factor VIII concentration during bypass was performed by a chromogenic method because a coagulation based assay would have been invalidated by the concurrent use of heparin. The postoperative regime of bolus versus continuous infusion was decided on pragmatic terms considering nursing expertise, stability of the factor VIII product, and venous access. It is the practice of the supervising hemophilia center to use a variety of recombinant factor VIII products to safeguard from supply shortages. Each individual patient will remain on the initially allocated product. The assay of Refacto (Wyeth Laboratories) does require use of a specific concentrate plasma standard, but the efficacy in establishing hemostasis is not significantly different from other factor VIII products.
Ann Thorac Surg 2006;81:336 –9
There is a concern that exposure of hemophilia patients to factor VIII at an early age may increase the risk of factor VIII inhibitor development [6]. Factor VIII inhibitors are antibodies that bind to exogenously administered factor VIII reducing or abolishing its efficacy. In cases of mild or moderate hemophilia A, these inhibitors may also bind to endogenous factor VIII, thus increasing the severity of the bleeding disorder. Both patients described had mild or moderate hemophilia A, neither had evidence for an inhibitor before surgery, and no inhibitor is evident in either patient after 17 and 24 months of follow-up, respectively. However, there is a need for ongoing inhibitor surveillance. The use of recombinant factor VIIa has been suggested as an alternative to factor VIII to avoid inhibitor development [7]. Leggett and colleagues [8] described a successful cardiac operation in a young boy with severe factor VIII deficiency with high titer of antibodies. Both of our infants had not received multiple transfusions before surgery and were negative for antibodies. The therapeutic regime to establish hemostasis in other coagulation factor deficiencies will depend on the nature and severity of the factor deficiency. Factor concentrates are available for deficiencies of all coagulation factors other than factor V. Concentrates may be prepared by recombinant DNA technology and be free of plasma; other products are prepared by plasma fraction-
Table 3. Guideline for Factor VIII Replacement Therapy in Cardiac Surgery Preoperatively Check factor VIII inhibitor levels preoperatively. Check baseline clotting and factor VIII levels. Establish reliable venous access—one for sampling and the other for administration of factor VIII. On the day of surgery Bolus of factor VIII to achieve factor VIII level of 100 IU/dL administered for 5 minutes, 2 to 3 hours prior to surgery. Then start continuous infusion of factor VIII at a rate of 10 ⫻ weight/hr (IU/hr)a—piggyback a normal saline infusion of about 10 mL/hr to alert staff to cannula tissuing. Check factor VIII level 1 hour later (target ⬎ 100 IU/dL prior to surgery) Repeat level preheparinization—give bolus if required (target ⬎ 100 IU/dL) and increase infusion rate. Repeat level 30 minutes into bypass—patient will need chromogenic factor VIII/heparin neutralization in the laboratory. Postoperatively Repeat levels at 4 to 6 hour intervals in the immediate postoperative period and titrate the infusion accordingly. Continue the infusion for 7 to 14 days postoperatively (checking factor VIII levels twice daily during the first 3 postoperative days and less frequently thereafter). Introduce bolus doses when factor VIII levels are predictable according to local practice. a Infusion rate (U/kg/hr) ⫽ desired plasma level (IU/mL) ⫻ clearance (mL/kg/hr). Initial estimated clearance ⫽ 10 mL/kg/hr. Desired plasma level ⫽ 1 IU/mL (⫽ 10 IU/dL or 100%). Initial infusion rate ⫽ 10 ⫻ wt/hr ⫽ 40 IU/hr.
Ann Thorac Surg 2006;81:339 – 41
References 1. MacKinlay N, Taper J, Renisson F, Richard K. Cardiac surgery and catheterisation in patients with haemophilia. Haemophilia 2000;6(2):84 – 8. 2. Nomura K, Nakumara Y, Yamagishi M, Yamamoto K, Hanada R. Perioperative management of ventricular septal defect and right coronary cusp prolapse in a patient with haemophilia A. Kyobu Geka (Japanese) 1994;47(13):1071– 4. 3. Nakajima H, Takada K, Taguchi A, et al. Anaesthetic management of hemophilia A carrier for palliative operation and radical repair of a cardiac anomaly. Maui-Japanese J Anesth 1992;41(3):460 –3. 4. Boilletot A, De Geeter B, Wiesel ML, et al. Surgical correction of interventricular communication with pulmonary stenosis in a haemophiliac. Arch Fr Pediatr 1983;40(7):571–3. 5. Rochat C, McFayden ML, Schwyzer R, Gillham A, Cruickshank A. Continuous infusion of intermediate – purity factor VIII in haemophilia patients undergoing elective surgery. Haemophilia 1995;5:181– 6. 6. Van der Bom JG, Mauser-Bunschoten EP, Fischer K, van den Berg HM. Age at first treatment and immune tolerance to factor VIII in severe hemophilia. Thromb Haemost 2003;89(3): 475–9. 7. Major surgery in haemophiliac patients with inhibitors using recombinant factor VIIa. Haemostasis 1996;26(Suppl 1):118 –23. 8. Leggett PL, Doyle D, Smith WB, et al. Elective cardiac operation in a patient with severe hemophilia and acquired factor VIII antibodies. J Thorac Cardiovasc Surg 1984;87(4):556 – 60. © 2006 by The Society of Thoracic Surgeons Published by Elsevier Inc
339
Infectious Ductal Aneurysm After Coil Embolization in an Infant Takeshi Shinkawa, MD, Masaaki Yamagishi, MD, Keisuke Shuntoh, MD, Katsuji Fujiwara, MD, Taiji Watanabe, MD, and Satomi Yoshida, MD Department of Pediatric Cardiovascular Surgery, Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
We report a case of ductal aneurysm after transcatheter coil embolization in an infant. The aneurysm was asymptomatic and was not detected until it ruptured during surgical intervention. We suspect that the aneurysm was induced by methicillin-resistant Staphylococcus aureus infection, as the resected aneurysmal wall was severely infiltrated by inflammatory cells and the patient had recurrent methicillin-resistant Staphylococcus aureus infection. We recommend remaining on guard against formation of a ductal aneurysm after coil embolization, especially in patients with associated recurrent bacteremia. (Ann Thorac Surg 2006;81:339 – 41) © 2006 by The Society of Thoracic Surgeons
T
ranscatheter coil embolization of the patent ductus arteriosus is widely used to treat patients with patent ductus arteriosus and pulmonary hypertension. We describe a 9-month-old girl who developed a ductal aneurysm after coil embolization. One week after birth, a girl with situs inversus, doubleoutlet right ventricle, large remote type ventricular septal defect, transposition of the great arteries, infundibular pulmonary stenosis, patent ductus arteriosus, and pulmonary hypertension developed necrotizing enterocolitis. She was treated with imipenem with immediate improvement in her inflammation, but a barium enema examination performed at 1 month of age showed severe stenosis of the sigmoid colon. At the age of 2 months, she was referred to our hospital. She had septic shock caused by methicillin-resistant Staphylococcus aureus (MRSA) and was treated with vancomycin and exchange transfusions. At the age of 3 months, she underwent resection of the stenotic colon and creation of a stoma. Frequent recurring respiratory infections and uncontrollable heart failure persisted, leading to a cardiac catheter examination, which was performed at 5 months of age and which revealed pulmonary hypertension with high pulmonary blood flow. To decrease pulmonary blood flow, we embolized the patent ductus arteriosus using a detachable coil with three 5-mm loops (Flipper, Cook, IN) at the age of 7 months (Fig 1). The patient’s general condition did Accepted for publication Sept 24, 2004. Address correspondence to Dr Shinkawa, Department of Pediatric Cardiovascular Surgery, Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kawaramachi, Hirokoji, Kamigyo-ku, Kyoto 602– 8566, Japan; e-mail: [email protected].
0003-4975/06/$32.00 doi:10.1016/j.athoracsur.2004.09.049
FEATURE ARTICLES
ation techniques. In principle, the use of plasma derived products should be avoided if a safe alternative is available. Desmopressin (1-desamino-8-D-arginine vasopressin) is a synthetic analogue of vasopressin and is used in cases of mild or moderate hemophilia A and certain subsets of von Willebrand’s disease. Use of this drug in appropriate patients results in the elevation of circulating plasma levels of factor VIII and von Willebrand factor sufficient enough to establish hemostasis. However, the use of this drug in neonates should be avoided because of the risk of hyponatremia; furthermore the efficacy of this approach would be questionable in cases of lifethreatening surgery requiring prolonged normalization of coagulation factor levels. Therefore, in practice, management of cases of cardiac surgery in neonates with hemophilia will require replacement with appropriate factor concentrate. A generic regime for all other bleeding disorders will be impractical given the varied half lives and hemostatic levels for other coagulation factors. In conclusion, children with hemophilia present an increased challenge to the cardiac surgical team. These two examples illustrate that cardiac operations using systemic heparinization can be safely performed in infants with hemophilia when carried out with preoperative and perioperative support from the hematology service, adequate replacement therapy using blood components, and careful monitoring of the coagulation status. Our guideline for factor VIII replacement therapy during and after cardiac surgery may be appropriate for other centers.
CASE REPORT SHINKAWA ET AL INFECTIOUS DUCTAL ANEURYSM AFTER COILING