Enoxiparin for long-term anticoagulation with the pediatric EXCOR left ventricular assist device
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《血管的通路杂志》
a Department of Thoracic and Cardiovascular Surgery, Klinik für Thorax-, Herz- und Gefchirurgie, Albert-Schweitzer Strae 33, D-48149 Münster, Germany
b Department of Pediatric Cardiology, University Hospital Münster, Germany
Abstract
We report on an 8-month-old child with end-stage heart failure, which was successfully transplanted after 5 months of mechanical circulatory support with the Excor Berlin Heart system using low molecular weight heparin instead of an oral anticoagulation.
Key Words: Pediatric heart failure; LVAD; Anticoagulation
1. Introduction
In pediatric patients, end-stage heart failure is rare but usually fatal. Cardiac transplantation remains the treatment of choice in most cases, but unfortunately it cannot be performed in many cases due to the tremendous shortage of donor hearts [1]. To solve this problem mechanical circulatory support devices were increasingly used to bridge children to heart transplantation. In Germany, the Medos device [2] and the Excor Berlin Heart have been introduced into clinical practice [3]. We report on a child with end-stage heart failure, which was successfully bridged to cardiac transplantation for more than 5 months with the Excor Berlin Heart using low molecular weight heparin instead of oral anticoagulants like e.g. phenprocoumon for long-term anticoagulation.
2. Case report
An 8-month-old female child (7200 g, 74 cm, body surface area 0.38 m2), with a previous normal development, presented to a rural hospital with a two-week history of vomiting, dehydration and acidosis. Soon after admission, echocardiography revealed a dilated heart. The young patient was immediately transferred to a specialized pediatric cardiology department. Repeated echocardiography confirmed dilative cardiomyopathy with a shortening fraction of 10% and a left ventricle diastolic diameter of 48 mm. Despite the use of beta-blockers, diuretics, angiotensin-converting-enzyme-inhibitors and digitalis the clinical condition deteriorated and admission to an intensive care unit with continuous inotropic support became necessary. The little patient was transferred to our university hospital for evaluation of cardiac transplantation. At admission, the child was awake, had spontaneous breathing, with systolic and diastolic heart murmurs under inotropic support and with no signs of neurological impairment. Blood tests were normal apart from a BNP (Brain Derived Natriuretic Protein) of 22173 U/l and slightly elevated liver enzymes. No obvious cause for the severe heart disease was found. When cardiovascular collapse mandating resuscitation occurred, a paracorporeal pneumatically driven Excor left ventricular assist device utilizing a 25 ml chamber was placed (Berlin Heart AG, Berlin, Germany). During extracorporeal circulation a 6-mm inflow cannula was inserted into the left ventricular apex and a 6-mm outflow cannula was connected to the ascending aorta. The pump flow was adjusted to 2.4 l/min. Within a few days the girl stabilized and she could be weaned from inotropic support. The initial anticoagulation merely consisted of i.v. heparin at a dosage of 400 units per kilogram body weight per day, guided by the aPTT (60–80 s). After removal of chest tubes, aspirin (5–30 mg/d) and clopidogrel (1–10 mg/d) were added to the anticoagulation regime. Its dosage was titrated to achieve a platelet inhibition of 70% or more during aggregometry (PAP-4, Molab, Berlin). On postoperative day 33 i.v. heparin was replaced by low molecular weight heparin (LMWH) (enoxiparin 10–15 mg/d), subcutaneously, once a day. The effect of LMWH was monitored by measurements of anti-Xa levels, where a target range of 0.5 to 1.0 U/ml was considered optimal (Fig. 1).
The further postoperative course was uneventful until day 124, when a transient ischemic attack occurred manifestating as an incomplete hemiplegia. The subsequently performed cranial CT scan was normal. The pump chamber was exchanged as a small thrombus deposition was evident (Fig. 2). The little patient recovered totally without any neurological impairment. A follow-up CT scan before discharge revealed a small hypodense subcortical lesion less than 1 cm in diameter. On day 154 of mechanical circulatory support a suitable donor organ was found and a successful orthotopic cardiac transplantation was performed.
3. Discussion
Pediatric long-term mechanical support is challenging as bleeding and thrombembolic complications frequently occur [4]. This case offers different interesting information. First of all, the pediatric Excor system allows mechanical support beyond 100 days with an acceptable risk. A comparable experience has been reported by the inventors of the Berlin Heart, which supported 18 children for a mean of 20 days [5]. We noticed a small thrombus deposition inside the pump chamber, which may occur early. As a very tiny thrombus deposition is empirically harmless and a pump exchange associated with certain risks (thrombus and air embolism!), we do not aggressively exchange pump chambers. Instead, we optimize anticoagulation and antiaggregation. Only in case of large thrombus formation or after an adverse neurological event we exchange the pump chamber. In our case, the latter could be easily performed on the intensive care unit within a few minutes. Moreover, this case proves the possibility of using subcutaneous administered LMWH instead of coumadin or phenprocoumon as oral anticoagulants. Its efficacy can be monitored by measuring anti-Xa levels and kept rather stable over a long period of time [6]. Additional platelet inhibition with aspirin and clopidogrel does not interfere.
In conclusion, this case illustrates that LMWH could be a simple and reliable alternative during long-term support with the pediatric Excor system. Further experience in a larger patient population is necessary to evaluate the safety of this new approach in comparison to the established anticoagulation strategies.
References
Boucek MM, Novick RJ, Bennett LE, Fiol B, Keck BM, Hosenpud JD. The Registry of the International Society for Heart and Lung Transplantation: second official paediatric report-1998. J Heart Lung Transplant 1998;17:1141–11460.
Throckmorton AL, Allaire PE, Gutgesell HP, Matherne GP, Olsen DB, Wood HG, Allaire JH, Patel SM. Pediatric circulatory support systems. ASAIO J 2002;48:216–221.
Hetzer R, Loebe M, Weng Y, Alexi-Meskhishvili V, Stiller B. Pulsatile pediatric ventricular assist devices: current results for bridge to transplantation. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 1999;2:157–176.
Weyand M, Kececioglu D, Kehl H, Schmid C, Loick HM, Vogt J, Scheld HH. Neonatal bridging to total orthotopic heart transplantation. Ann Thorac Surg 1998;66:519–522.
Stiller B, Hetzer R, Weng Y, Hummel M, Hennig E, Nadgyman N, Ewert P, Lemkuhl H, Lange P. Heart transplantation in children after mechanical circulatory support with pulsatile pneumatic assist device. J Heart Lung Transplant 2003;22:1201–1208.
Ho SH, Wu JK, Hamilton DP, Dix DB, Wadsworth LD. An assessment of published pediatric dosage guidelines for enoxiparin: a retrospective review. J Pediatr Hematol Oncol 2004;26:561–566.(Daniele Camboni, Christof)
b Department of Pediatric Cardiology, University Hospital Münster, Germany
Abstract
We report on an 8-month-old child with end-stage heart failure, which was successfully transplanted after 5 months of mechanical circulatory support with the Excor Berlin Heart system using low molecular weight heparin instead of an oral anticoagulation.
Key Words: Pediatric heart failure; LVAD; Anticoagulation
1. Introduction
In pediatric patients, end-stage heart failure is rare but usually fatal. Cardiac transplantation remains the treatment of choice in most cases, but unfortunately it cannot be performed in many cases due to the tremendous shortage of donor hearts [1]. To solve this problem mechanical circulatory support devices were increasingly used to bridge children to heart transplantation. In Germany, the Medos device [2] and the Excor Berlin Heart have been introduced into clinical practice [3]. We report on a child with end-stage heart failure, which was successfully bridged to cardiac transplantation for more than 5 months with the Excor Berlin Heart using low molecular weight heparin instead of oral anticoagulants like e.g. phenprocoumon for long-term anticoagulation.
2. Case report
An 8-month-old female child (7200 g, 74 cm, body surface area 0.38 m2), with a previous normal development, presented to a rural hospital with a two-week history of vomiting, dehydration and acidosis. Soon after admission, echocardiography revealed a dilated heart. The young patient was immediately transferred to a specialized pediatric cardiology department. Repeated echocardiography confirmed dilative cardiomyopathy with a shortening fraction of 10% and a left ventricle diastolic diameter of 48 mm. Despite the use of beta-blockers, diuretics, angiotensin-converting-enzyme-inhibitors and digitalis the clinical condition deteriorated and admission to an intensive care unit with continuous inotropic support became necessary. The little patient was transferred to our university hospital for evaluation of cardiac transplantation. At admission, the child was awake, had spontaneous breathing, with systolic and diastolic heart murmurs under inotropic support and with no signs of neurological impairment. Blood tests were normal apart from a BNP (Brain Derived Natriuretic Protein) of 22173 U/l and slightly elevated liver enzymes. No obvious cause for the severe heart disease was found. When cardiovascular collapse mandating resuscitation occurred, a paracorporeal pneumatically driven Excor left ventricular assist device utilizing a 25 ml chamber was placed (Berlin Heart AG, Berlin, Germany). During extracorporeal circulation a 6-mm inflow cannula was inserted into the left ventricular apex and a 6-mm outflow cannula was connected to the ascending aorta. The pump flow was adjusted to 2.4 l/min. Within a few days the girl stabilized and she could be weaned from inotropic support. The initial anticoagulation merely consisted of i.v. heparin at a dosage of 400 units per kilogram body weight per day, guided by the aPTT (60–80 s). After removal of chest tubes, aspirin (5–30 mg/d) and clopidogrel (1–10 mg/d) were added to the anticoagulation regime. Its dosage was titrated to achieve a platelet inhibition of 70% or more during aggregometry (PAP-4, Molab, Berlin). On postoperative day 33 i.v. heparin was replaced by low molecular weight heparin (LMWH) (enoxiparin 10–15 mg/d), subcutaneously, once a day. The effect of LMWH was monitored by measurements of anti-Xa levels, where a target range of 0.5 to 1.0 U/ml was considered optimal (Fig. 1).
The further postoperative course was uneventful until day 124, when a transient ischemic attack occurred manifestating as an incomplete hemiplegia. The subsequently performed cranial CT scan was normal. The pump chamber was exchanged as a small thrombus deposition was evident (Fig. 2). The little patient recovered totally without any neurological impairment. A follow-up CT scan before discharge revealed a small hypodense subcortical lesion less than 1 cm in diameter. On day 154 of mechanical circulatory support a suitable donor organ was found and a successful orthotopic cardiac transplantation was performed.
3. Discussion
Pediatric long-term mechanical support is challenging as bleeding and thrombembolic complications frequently occur [4]. This case offers different interesting information. First of all, the pediatric Excor system allows mechanical support beyond 100 days with an acceptable risk. A comparable experience has been reported by the inventors of the Berlin Heart, which supported 18 children for a mean of 20 days [5]. We noticed a small thrombus deposition inside the pump chamber, which may occur early. As a very tiny thrombus deposition is empirically harmless and a pump exchange associated with certain risks (thrombus and air embolism!), we do not aggressively exchange pump chambers. Instead, we optimize anticoagulation and antiaggregation. Only in case of large thrombus formation or after an adverse neurological event we exchange the pump chamber. In our case, the latter could be easily performed on the intensive care unit within a few minutes. Moreover, this case proves the possibility of using subcutaneous administered LMWH instead of coumadin or phenprocoumon as oral anticoagulants. Its efficacy can be monitored by measuring anti-Xa levels and kept rather stable over a long period of time [6]. Additional platelet inhibition with aspirin and clopidogrel does not interfere.
In conclusion, this case illustrates that LMWH could be a simple and reliable alternative during long-term support with the pediatric Excor system. Further experience in a larger patient population is necessary to evaluate the safety of this new approach in comparison to the established anticoagulation strategies.
References
Boucek MM, Novick RJ, Bennett LE, Fiol B, Keck BM, Hosenpud JD. The Registry of the International Society for Heart and Lung Transplantation: second official paediatric report-1998. J Heart Lung Transplant 1998;17:1141–11460.
Throckmorton AL, Allaire PE, Gutgesell HP, Matherne GP, Olsen DB, Wood HG, Allaire JH, Patel SM. Pediatric circulatory support systems. ASAIO J 2002;48:216–221.
Hetzer R, Loebe M, Weng Y, Alexi-Meskhishvili V, Stiller B. Pulsatile pediatric ventricular assist devices: current results for bridge to transplantation. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 1999;2:157–176.
Weyand M, Kececioglu D, Kehl H, Schmid C, Loick HM, Vogt J, Scheld HH. Neonatal bridging to total orthotopic heart transplantation. Ann Thorac Surg 1998;66:519–522.
Stiller B, Hetzer R, Weng Y, Hummel M, Hennig E, Nadgyman N, Ewert P, Lemkuhl H, Lange P. Heart transplantation in children after mechanical circulatory support with pulsatile pneumatic assist device. J Heart Lung Transplant 2003;22:1201–1208.
Ho SH, Wu JK, Hamilton DP, Dix DB, Wadsworth LD. An assessment of published pediatric dosage guidelines for enoxiparin: a retrospective review. J Pediatr Hematol Oncol 2004;26:561–566.(Daniele Camboni, Christof)