Gen Thorac Cardiovasc Surg DOI 10.1007/s11748-015-0621-0
CASE REPORT
Severe hemolytic anemia caused by the NIPRO extracorporeal left ventricular assist device Ikuko Shibasaki1 • Toshiyuki Kuwata1 • Go Tsuchiya1 • Hironaga Ogawa1 • Yasuyuki Yamada1 • Shigeru Toyoda2 • Teruo Inoue2 • Hirotsugu Fukuda1
Received: 2 October 2015 / Accepted: 23 December 2015 Ó The Japanese Association for Thoracic Surgery 2016
Abstract A 56-year-old woman with dilated cardiomyopathy underwent mitral and tricuspid annuloplasty, and simultaneous deployment of an extracorporeal left ventricular assist device (LVAD). Subsequently, she developed hemolytic anemia. Although the LVAD system was repeatedly exchanged and the mitral annular ring was removed, her hemolytic anemia did not improve. Finally, the NIPRO LVAD was replaced with Gyro PumpÒ, and her anemia was ameliorated. It appears important to consider the possibility of hemolytic anemia as a LVAD-related complication, although it would be rare.
implantable LVAD deployment is about 3.1 % [3], there have been no reports on hemolytic anemia after extracorporeal LVAD deployment. The Medtronic Hall valve, a monoleaflet tilting disc valvular prosthesis, that is placed at the inlet/outlet parts of the pump [4], may potentially cause hemolysis. However, the precise mechanism of LVADinduced hemolysis is unknown. We report on a patient who developed severe hemolytic anemia shortly after deployment of a NIPRO LVAD.
Case report Keywords NIPRO LVAD Hemolytic anemia Dilated cardiomyopathy
Introduction The NIPRO extracorporeal left ventricular assist device (LVAD) (NIPRO, Osaka, Japan) has long been the most frequently used mechanical circulatory support device for the treatment of end-stage heart failure in Japan [1]. As described in previous reports, long-term use of the NIPRO LVAD not only limits patients’ movement, but also involves serious complications such as stroke and infection [2]. Although the incidence of hemolytic anemia after
& Ikuko Shibasaki [email protected] 1
Department of Cardiac and Vascular Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan
2
Department of Cardiovascular Medicine, Dokkyo Medical University, School of Medicine, Tochigi, Japan
A 56-year-old woman with dilated cardiomyopathy was admitted to our hospital on an emergency basis because of cardiopulmonary arrest. Two years prior, she had symptoms of heart failure and was diagnosed with idiopathic dilated cardiomyopathy (DCM) by myocardial biopsy. Since then, she has been treated with medications including angiotensin converting enzyme inhibitors and beta blockers at our out-patient clinic. After successful cardiopulmonary resuscitation by the first responder, the patient was brought to our hospital. At this admission, her hemodynamic state was destabilized, because of severe left ventricular dysfunction (ejection fraction 20 %) with both mitral and tricuspid regurgitation. Despite aggressive medical treatment, her heart failure was not improved. Repeated ventricular fibrillation occurred that required external shock therapy. Since there was progressive multiple organ failure associated with impaired left ventricular function, the patient underwent mechanical circulatory support with intra-aortic balloon pumping and percutaneous cardiopulmonary support. Nevertheless, her condition did not improve. Thus, on the 14th hospital day, surgical treatment including annuloplasty for both the mitral and tricuspid valves was
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performed. In addition, a NIPRO LVAD (VCT-50x) was simultaneously placed. After surgery, her hemoglobin (Hb) level decreased and her lactate dehydrogenase (LDH), total bilirubin (T-Bil) and indirect bilirubin (I-Bil) levels increased. On the 42nd postoperative day, the following laboratory results were obtained Hb 6.1 g/dL, T-Bil 1.4 mg/dL, I-Bil 0.6 mg/dL, LDH 1125 IU/L, platelet (Plt) 19.3 9 104 lL, prothrombin time international normalized ratio (PT-INR) 2.57 and activated partial thromboplastin time (APTT) 51.8 s. In addition to these findings, the presence of hemoglobinuria suggested that there was hemolytic anemia. Computed tomography (CT) and echocardiography showed no evidence of flexion of the internal artificial vessel grafts that were connected to the inflow/outflow cannulas of the extracorporeal LVAD, which could have caused hemolysis. Autoimmune or drug-induced immune hemolytic anemia was excluded by a negative Coombs’ test and erythrocyte morphology findings, and paroxysmal nocturnal hemoglobinuria was also eliminated by a negative Ham test. Trans-thoracic and trans-esophageal echocardiography demonstrated a regurgitant jet across the mitral valve that was mild but impinged on the posterior side of the annular ring. Therefore, in addition to the LVAD device itself, the mitral regurgitant jet might also have been the cause of hemolysis. First, we adjusted the driving conditions several times, but did not succeed in preventing the progression of hemolysis. Next, we replaced the LVAD chamber itself. Since blood clot formation in the chamber was poorly controlled despite optimal anti-coagulant therapy, we replaced the chamber three times. The VCT-50 (Nipro Co.) console was used for the NIPRO-VAD. This was performed while the drive pressure (DP), vacuum pressure (VP), beating rate (BR) and % systolic fraction (%Sys) were fixed at 200 mmHg, -50 mmHg, 90 bpm and 30 %, respectively. We also tried changing the DP (200–190 mmHg), VP (-50 to -30 mmHg), BR (90–110 bpm) and %Sys (30–40 %). Nevertheless, her hemolytic anemia was aggravated. Moreover, the mitral annular ring, which we considered to be another potential cause of hemolysis, was surgically removed. Nevertheless, her hemolytic anemia became worse. During the course of LVAD therapy, her Hb level decreased minimally to 4.3 g/dL, and her levels of T-Bil and I-Bil increased maximally to 2.6 and 2.0 mg/dL, respectively. Finally, on the 142nd postoperative day the NIPRO LVAD chamber (VCT-50) was replaced with a Gyro PumpÒ (Medtronic Inc. CFP), a centrifugal pump device for extracorporeal perfusion. The Gyro Pump was connected to the NIPRO cannula. Immediately after the pump was exchanged, her hemoglobinuria disappeared. The next day, her levels of Hb and LDH reached 7.8 g/dL and
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774 IU/L, and her anemia was promptly ameliorated. One month later, her Hb level increased to over 9.0 g/dL, and her levels of LDH, T-Bil and D-Bil decreased to values below 200 IU/L, 0.5 mg/dL and 0.2 mg/dL, respectively. Since she had an indication for heart transplantation, the Heart Mate IIÒ (Thoratec Corporation, Pleasanton, CA, USA), an implantable LVAD, was implanted about 3 months after deployment of the Gyro Pump. Recurrence of her anemia after implantation of the Heart Mate IIÒ was not observed (Fig. 1).
Discussion Hemolytic anemia occurred within 2 months after surgery in the present case and was characterized by rapid progression after onset. We first considered mechanical hemolytic anemia due to the cannulas used in the NIPRO LVAD. Some reports demonstrated hemolytic anemia induced by graft flexion after the surgical treatment of acute aortic dissection [5, 6]. Therefore, we performed CT and echocardiography to carefully investigate the inflow/ outflow cannulas of the extracorporeal LVAD. However, flexion of the grafts connecting the cannulas was absent. During her clinical course, we suspected that the extracorporeal LVAD itself might have been responsible for hemolysis. At the same time, we considered autoimmune and drug-induced immune hemolytic anemia, but blood tests excluded those possibilities. Thus, mechanical hemolysis was suspected. In some reports, hemolytic anemia after mitral annuloplasty was noted, especially that due to the use of an annuloplasty ring [7, 8]. In our case, postoperative trans-thoracic and trans-esophageal echocardiography showed a small regurgitant jet striking the ring. However, her anemia was not improved e after the ring was removed. Although the mechanism of hemolytic anemia was not clear, we suspected mechanical hemolytic anemia due to the NIPRO LVAD chamber. Therefore, it was replaced with a Gyro PumpÒ, and this resulted in the prompt improvement of her hemolysis. According to a report by Genovese et al. [3], early complications with an implantable VAD were seen in 89 % of reported cases, including bleeding (47.7 %), infection (42.1 %) and arrhythmia (36.4 %). However, only 3.1 % showed hemolytic anemia, and its mechanism was not determined. There have been no reports of hemolytic anemia caused by an extracorporeal LVAD, especially the NIPRO LVAD. In our case, blood clot formation in the chamber was poorly controlled despite optimal anti-coagulant therapy. Although blood clot formation in the chamber is a potential cause of hemolysis, replacing the LVAD chamber three times did not improve the hemolytic anemia. Thus, we speculate that the Medtronic Hall valve,
Gen Thorac Cardiovasc Surg Fig. 1 Clinical course of the presented case after mitral and tricuspid annuloplasty, and simultaneous deployment of an extracorporeal left ventricular assist device
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1/14 NIPRO LVAD deployment Mitral and Tricuspid annuloplasty
a monoleaflet tilting disc valvular prosthesis that is placed at the inlet/outlet parts of the pump, was a potential cause of hemolysis in our patient. In addition, we also consider the difference between pulsatile and continuous flow LVAD is very critical, because switching from a pulsatile flow system (NIPRO LVAD) to a continuous flow system (Gyro PumpÒ) improved her hemolytic anemia. However, we could not determine the precise mechanism for LVADinduced hemolysis from our experience with this case. Hemolytic anemia is a rare complication of deployment of an extracorporeal LVAD. Nevertheless, it appears important to always consider the possibility of hemolytic anemia as an LVAD-related complication. Compliance with ethical standards Conflict of interest The authors declare that they have received no financial support and have no relationships that may pose a conflict of interest.
5/16 Removal of mitral valve ring
6/10 GyroPump deployment
9/26 Heart Mate II implantation
2. Saito S, Matsumiya G, Sakaguchi T, Miyagawa S, Yoshikawa Y, Yamauchi T, et al. Risk factor analysis of long-term support with left ventricular assist system. Circ J. 2010;74:715–22. 3. Genovese EA, Dew MA, Teuteberg JJ, Simon MA, Kay J, Siegenthaler MP, Bhama JK, Bermudez CA, Lockard KL, et al. Incidence and patterns of adverse event onset during the first 60 days after ventricular assist device implantation. Ann Thorac Surg. 2009;88:1162–70. 4. Kimura M, Nishimura T, Kinoshita O, Kashiwa K, Kyo S, Ono M. Hemodynamic influence of tilting disc valve type on pump performance with the NIPRO-ventricular assist device. J Artif Organs. 2012;15:134–9. 5. Izumi S, Tano K, Horike K, Kaihotsu N. Repeat surgery for hemolysis 6 tears after replacement of the ascending aorta for acute aortic dissection. Jpn J Thorac Cardiovasc Surg. 2003;51:459–61. 6. Sekine Y, Yamamoto S, Fujikawa T, Oshima S, Ono M, Sasaguri S. Haemolytic anemia resulting from the surgical repair of acute type A aortic dissection. Interact CardioVasc Thorac Surg. 2014;18:230–3. 7. Wilson JH, Rath R, Glaser R, Panke T. Severe hemolysis after incomplete mitral valve repair. Ann Thoac Surg. 1990;50:136–7. 8. Cardoso C, Cachado P, Garcia T. Hemolytic anemia after mitral valve repair: a case report. BMS Res Notes. 2013;6:165.
References 1. Morita S. An old ventricular assist device still working for patients with end-stage heart failure in Japan. Circ J. 2011;75:53–4.
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CASE REPORT
Severe hemolytic anemia caused by the NIPRO extracorporeal left ventricular assist device Ikuko Shibasaki1 • Toshiyuki Kuwata1 • Go Tsuchiya1 • Hironaga Ogawa1 • Yasuyuki Yamada1 • Shigeru Toyoda2 • Teruo Inoue2 • Hirotsugu Fukuda1
Received: 2 October 2015 / Accepted: 23 December 2015 Ó The Japanese Association for Thoracic Surgery 2016
Abstract A 56-year-old woman with dilated cardiomyopathy underwent mitral and tricuspid annuloplasty, and simultaneous deployment of an extracorporeal left ventricular assist device (LVAD). Subsequently, she developed hemolytic anemia. Although the LVAD system was repeatedly exchanged and the mitral annular ring was removed, her hemolytic anemia did not improve. Finally, the NIPRO LVAD was replaced with Gyro PumpÒ, and her anemia was ameliorated. It appears important to consider the possibility of hemolytic anemia as a LVAD-related complication, although it would be rare.
implantable LVAD deployment is about 3.1 % [3], there have been no reports on hemolytic anemia after extracorporeal LVAD deployment. The Medtronic Hall valve, a monoleaflet tilting disc valvular prosthesis, that is placed at the inlet/outlet parts of the pump [4], may potentially cause hemolysis. However, the precise mechanism of LVADinduced hemolysis is unknown. We report on a patient who developed severe hemolytic anemia shortly after deployment of a NIPRO LVAD.
Case report Keywords NIPRO LVAD Hemolytic anemia Dilated cardiomyopathy
Introduction The NIPRO extracorporeal left ventricular assist device (LVAD) (NIPRO, Osaka, Japan) has long been the most frequently used mechanical circulatory support device for the treatment of end-stage heart failure in Japan [1]. As described in previous reports, long-term use of the NIPRO LVAD not only limits patients’ movement, but also involves serious complications such as stroke and infection [2]. Although the incidence of hemolytic anemia after
& Ikuko Shibasaki [email protected] 1
Department of Cardiac and Vascular Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan
2
Department of Cardiovascular Medicine, Dokkyo Medical University, School of Medicine, Tochigi, Japan
A 56-year-old woman with dilated cardiomyopathy was admitted to our hospital on an emergency basis because of cardiopulmonary arrest. Two years prior, she had symptoms of heart failure and was diagnosed with idiopathic dilated cardiomyopathy (DCM) by myocardial biopsy. Since then, she has been treated with medications including angiotensin converting enzyme inhibitors and beta blockers at our out-patient clinic. After successful cardiopulmonary resuscitation by the first responder, the patient was brought to our hospital. At this admission, her hemodynamic state was destabilized, because of severe left ventricular dysfunction (ejection fraction 20 %) with both mitral and tricuspid regurgitation. Despite aggressive medical treatment, her heart failure was not improved. Repeated ventricular fibrillation occurred that required external shock therapy. Since there was progressive multiple organ failure associated with impaired left ventricular function, the patient underwent mechanical circulatory support with intra-aortic balloon pumping and percutaneous cardiopulmonary support. Nevertheless, her condition did not improve. Thus, on the 14th hospital day, surgical treatment including annuloplasty for both the mitral and tricuspid valves was
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performed. In addition, a NIPRO LVAD (VCT-50x) was simultaneously placed. After surgery, her hemoglobin (Hb) level decreased and her lactate dehydrogenase (LDH), total bilirubin (T-Bil) and indirect bilirubin (I-Bil) levels increased. On the 42nd postoperative day, the following laboratory results were obtained Hb 6.1 g/dL, T-Bil 1.4 mg/dL, I-Bil 0.6 mg/dL, LDH 1125 IU/L, platelet (Plt) 19.3 9 104 lL, prothrombin time international normalized ratio (PT-INR) 2.57 and activated partial thromboplastin time (APTT) 51.8 s. In addition to these findings, the presence of hemoglobinuria suggested that there was hemolytic anemia. Computed tomography (CT) and echocardiography showed no evidence of flexion of the internal artificial vessel grafts that were connected to the inflow/outflow cannulas of the extracorporeal LVAD, which could have caused hemolysis. Autoimmune or drug-induced immune hemolytic anemia was excluded by a negative Coombs’ test and erythrocyte morphology findings, and paroxysmal nocturnal hemoglobinuria was also eliminated by a negative Ham test. Trans-thoracic and trans-esophageal echocardiography demonstrated a regurgitant jet across the mitral valve that was mild but impinged on the posterior side of the annular ring. Therefore, in addition to the LVAD device itself, the mitral regurgitant jet might also have been the cause of hemolysis. First, we adjusted the driving conditions several times, but did not succeed in preventing the progression of hemolysis. Next, we replaced the LVAD chamber itself. Since blood clot formation in the chamber was poorly controlled despite optimal anti-coagulant therapy, we replaced the chamber three times. The VCT-50 (Nipro Co.) console was used for the NIPRO-VAD. This was performed while the drive pressure (DP), vacuum pressure (VP), beating rate (BR) and % systolic fraction (%Sys) were fixed at 200 mmHg, -50 mmHg, 90 bpm and 30 %, respectively. We also tried changing the DP (200–190 mmHg), VP (-50 to -30 mmHg), BR (90–110 bpm) and %Sys (30–40 %). Nevertheless, her hemolytic anemia was aggravated. Moreover, the mitral annular ring, which we considered to be another potential cause of hemolysis, was surgically removed. Nevertheless, her hemolytic anemia became worse. During the course of LVAD therapy, her Hb level decreased minimally to 4.3 g/dL, and her levels of T-Bil and I-Bil increased maximally to 2.6 and 2.0 mg/dL, respectively. Finally, on the 142nd postoperative day the NIPRO LVAD chamber (VCT-50) was replaced with a Gyro PumpÒ (Medtronic Inc. CFP), a centrifugal pump device for extracorporeal perfusion. The Gyro Pump was connected to the NIPRO cannula. Immediately after the pump was exchanged, her hemoglobinuria disappeared. The next day, her levels of Hb and LDH reached 7.8 g/dL and
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774 IU/L, and her anemia was promptly ameliorated. One month later, her Hb level increased to over 9.0 g/dL, and her levels of LDH, T-Bil and D-Bil decreased to values below 200 IU/L, 0.5 mg/dL and 0.2 mg/dL, respectively. Since she had an indication for heart transplantation, the Heart Mate IIÒ (Thoratec Corporation, Pleasanton, CA, USA), an implantable LVAD, was implanted about 3 months after deployment of the Gyro Pump. Recurrence of her anemia after implantation of the Heart Mate IIÒ was not observed (Fig. 1).
Discussion Hemolytic anemia occurred within 2 months after surgery in the present case and was characterized by rapid progression after onset. We first considered mechanical hemolytic anemia due to the cannulas used in the NIPRO LVAD. Some reports demonstrated hemolytic anemia induced by graft flexion after the surgical treatment of acute aortic dissection [5, 6]. Therefore, we performed CT and echocardiography to carefully investigate the inflow/ outflow cannulas of the extracorporeal LVAD. However, flexion of the grafts connecting the cannulas was absent. During her clinical course, we suspected that the extracorporeal LVAD itself might have been responsible for hemolysis. At the same time, we considered autoimmune and drug-induced immune hemolytic anemia, but blood tests excluded those possibilities. Thus, mechanical hemolysis was suspected. In some reports, hemolytic anemia after mitral annuloplasty was noted, especially that due to the use of an annuloplasty ring [7, 8]. In our case, postoperative trans-thoracic and trans-esophageal echocardiography showed a small regurgitant jet striking the ring. However, her anemia was not improved e after the ring was removed. Although the mechanism of hemolytic anemia was not clear, we suspected mechanical hemolytic anemia due to the NIPRO LVAD chamber. Therefore, it was replaced with a Gyro PumpÒ, and this resulted in the prompt improvement of her hemolysis. According to a report by Genovese et al. [3], early complications with an implantable VAD were seen in 89 % of reported cases, including bleeding (47.7 %), infection (42.1 %) and arrhythmia (36.4 %). However, only 3.1 % showed hemolytic anemia, and its mechanism was not determined. There have been no reports of hemolytic anemia caused by an extracorporeal LVAD, especially the NIPRO LVAD. In our case, blood clot formation in the chamber was poorly controlled despite optimal anti-coagulant therapy. Although blood clot formation in the chamber is a potential cause of hemolysis, replacing the LVAD chamber three times did not improve the hemolytic anemia. Thus, we speculate that the Medtronic Hall valve,
Gen Thorac Cardiovasc Surg Fig. 1 Clinical course of the presented case after mitral and tricuspid annuloplasty, and simultaneous deployment of an extracorporeal left ventricular assist device
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1/14 NIPRO LVAD deployment Mitral and Tricuspid annuloplasty
a monoleaflet tilting disc valvular prosthesis that is placed at the inlet/outlet parts of the pump, was a potential cause of hemolysis in our patient. In addition, we also consider the difference between pulsatile and continuous flow LVAD is very critical, because switching from a pulsatile flow system (NIPRO LVAD) to a continuous flow system (Gyro PumpÒ) improved her hemolytic anemia. However, we could not determine the precise mechanism for LVADinduced hemolysis from our experience with this case. Hemolytic anemia is a rare complication of deployment of an extracorporeal LVAD. Nevertheless, it appears important to always consider the possibility of hemolytic anemia as an LVAD-related complication. Compliance with ethical standards Conflict of interest The authors declare that they have received no financial support and have no relationships that may pose a conflict of interest.
5/16 Removal of mitral valve ring
6/10 GyroPump deployment
9/26 Heart Mate II implantation
2. Saito S, Matsumiya G, Sakaguchi T, Miyagawa S, Yoshikawa Y, Yamauchi T, et al. Risk factor analysis of long-term support with left ventricular assist system. Circ J. 2010;74:715–22. 3. Genovese EA, Dew MA, Teuteberg JJ, Simon MA, Kay J, Siegenthaler MP, Bhama JK, Bermudez CA, Lockard KL, et al. Incidence and patterns of adverse event onset during the first 60 days after ventricular assist device implantation. Ann Thorac Surg. 2009;88:1162–70. 4. Kimura M, Nishimura T, Kinoshita O, Kashiwa K, Kyo S, Ono M. Hemodynamic influence of tilting disc valve type on pump performance with the NIPRO-ventricular assist device. J Artif Organs. 2012;15:134–9. 5. Izumi S, Tano K, Horike K, Kaihotsu N. Repeat surgery for hemolysis 6 tears after replacement of the ascending aorta for acute aortic dissection. Jpn J Thorac Cardiovasc Surg. 2003;51:459–61. 6. Sekine Y, Yamamoto S, Fujikawa T, Oshima S, Ono M, Sasaguri S. Haemolytic anemia resulting from the surgical repair of acute type A aortic dissection. Interact CardioVasc Thorac Surg. 2014;18:230–3. 7. Wilson JH, Rath R, Glaser R, Panke T. Severe hemolysis after incomplete mitral valve repair. Ann Thoac Surg. 1990;50:136–7. 8. Cardoso C, Cachado P, Garcia T. Hemolytic anemia after mitral valve repair: a case report. BMS Res Notes. 2013;6:165.
References 1. Morita S. An old ventricular assist device still working for patients with end-stage heart failure in Japan. Circ J. 2011;75:53–4.
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