- Email: [email protected]
Mitral Valve Replacement With Cardiopulmonary Bypass in a Patient With Pyruvate Kinase Deficiency
Author’s Accepted Manuscript Mitral Valve Replacement with Cardiopulmonary Bypass in Patient with Pyruvate Kinase Deficiency – A Case Report Shakuntala Basantwani, Balasaheb Govardhane, Shital Shinde, Bharati Tendolkar www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1053-0770(16)00308-6 http://dx.doi.org/10.1053/j.jvca.2016.03.146 YJCAN3628
To appear in: Journal of Cardiothoracic and Vascular Anesthesia Received date: 12 January 2016 Cite this article as: Shakuntala Basantwani, Balasaheb Govardhane, Shital Shinde and Bharati Tendolkar, Mitral Valve Replacement with Cardiopulmonary Bypass in Patient with Pyruvate Kinase Deficiency – A Case Report, Journal of Cardiothoracic and Vascular Anesthesia, http://dx.doi.org/10.1053/j.jvca.2016.03.146 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Mitral valve replacement with cardiopulmonary bypass in patient with Pyruvate kinase deficiency – A case report
Authors: Dr. Shakuntala Basantwani – Corresponding Author Mobile Number: +91-9819018461 Institution: Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai 400022 Email : [email protected]
Dr. Balasaheb Govardhane Dr. Shital Shinde Dr. Bharati Tendolkar
INTRODUCTION Red cell Pyruvate Kinase (PK) deficiency is the most common enzyme abnormality in the Embeden Meyerhof pathway of glycolysis in humans, first reported by Valentine et al in 1961. It is an inherited autosomal recessive metabolic disorder which affects the survival of red blood cell. It is caused by mutations in PKLR gene (Pyruvate kinase Liver and Red Blood Cells), The prevalence rate of heterozygous carriers of chromosome 1 deficient PK –LR gene is believed to be approximately 1%. Beutler and Gelbart estimated the incidence of PK deficiency in the United States to be 1:20,000. However, the incidence is much higher in remote and exclusive communities such as the Amish in Pennsylvania and Ohio and some communities in southern Utah.
1,2,3,4
. PK deficiency is not uncommon in India but the data on its prevalence in Indian
population is lacking. The clinical severity ranges from mildly compensated anemia to severe anemia of childhood and unconjugated hyperbilirubinemia requiring exchange transfusion5. Open-heart surgery for cardiac lesions (congenital or acquired), in patients with hematologic diseases, although infrequent, presents potential management problems during the perioperative period. Cardiopulmonary bypass (CPB) involves contact of blood with bypass circuit surfaces, hypothermia, hypo perfusion and reperfusion in which cell damage is likely to occur6. Application of CPB for patients with PK deficiency can result in fatal hematologic complications. The literature on patients with pyruvate kinase deficiency undergoing cardiac surgery is rare, therefore the authors wish to share their experience and strategy in the management of such patients. The patient’s parents were informed regarding our intention to publish the case and also agreed for his blood sample being sent for free hemoglobin analysis. Therapeutic and other diagnostic
procedures in this case did not change with respect to our standard guidelines, so local ethics committee approval was not required.
CASE REPORT A 7-year-old male child weighing 15kg was admitted to our hospital with rheumatic heart disease having severe mitral restenosis and history of jaundice with history of multiple blood transfusion for past 1 year. Child was previously diagnosed as a case of pyruvate kinase deficiency in a child care hospital where he was treated for RHD and jaundice prior to the admission. He also had undergone Balloon mitral valvotomy (BMV) 6 months back for severe mitral stenosis. Routine blood test showed Hemoglobin 7.3g%, anisopoikilocytosis, Total leucocyte count of 4200, Total bilirubin of 2.48 (D-0.98, I-1.5) (Table 1) with normal liver enzymes and renal function test. Ultrasonography revealed moderate hepatosplenomegaly. Blood level of Pyruvate kinase was 6.9 U/g Hb (normal value 9-13 U/g Hb) (Table 1). Normal reticulocyte counts and normal red cell osmotic fragility indicated the lack of active hemolysis. Preoperative 2 dimensional echocardiography revealed rheumatic heart disease with post (BMV), severe Mitral stenosis (Mitral valve area 0 .6 cm2), moderate Mitral regurgitation and moderate tricuspid regurgitation with severe pulmonary arterial hypertension (70 mmHg) and Right ventricle pressure overload pattern with Wilkin score 10 “(Figure 1)”. Child was receiving Digoxin and furosemide. In the preoperative period, anemia was corrected with one unit packed red cell and General anesthesia was induced with Injection Propofol and Rocuronium following premedication with midazolam and fentanyl and intubated with 5.5 cuffed endotracheal tube. Depth of anesthesia was maintained with infusions of rocuronium and Fentanyl, desflurane.
Median strenotomy was employed and CPB was initiated post heparinization with standard aortobicaval cannulation. Bypass circuit was primed with two units of fresh blood. Intermittent ante grade warm blood hyperkalemic cardioplegia was administered every 20 min to provide myocardial protection. Through a right atrial trans septal approach, mitral valve was replaced with TTK Chitra 19 Aortic valve in reverse position valve in view of small size annulus and tricuspid ring annuloplasty was performed. Normothermia (36°C) and mean arterial blood pressure around 70 mm Hg was maintained throughout the procedure. During the bypass period, urine output was maintained with the use of Mannitol 50 ml and furosemide 20 mg. Child was gradually weaned off from CPB with heart rate of 120/min and BP104/60 mm of Hg with ionotropic supports of dopamine 5ug/kg/min, adrenaline 0.2ug/kg/min, 0.3mg/kg /min and Epicardial pacing. Duration of CPB was 70 min and aortic cross clamp time was 52 mins. Immediately after coming off CPB, 1 unit of fresh frozen plasma and two units of platelets were transfused in view on inadequate hemostasis. Hemoglobinuria was not observed. Child was mechanically ventilated overnight and extubated next morning. The total volume of blood in the chest drainage system was 100ml in 24 hrs. One unit of packed cell transfusion was used to restore the hemoglobin level to 8.5. Postoperative analgesia was maintained with IV Paracetamol 15mg/kg and injection Tramadol 1mg/kg 8 hourly. In view of the uncertain tolerance of the abnormal red cells to cardiopulmonary bypass in PK deficiency, free plasma hemoglobin, liver and renal function tests, urine samples were reviewed on the first postoperative day and showed slight hemolysis in the form of elevated bilirubin in the blood sample and elevated bilirubin and urobilinogen in the urine with normal renal functions. The levels of these parameters slowly reduced during the next postoperative days and the patient
was discharged on the seventh postoperative day. However, at six months follow up, child was found to have anemia, jaundice and marked reduction in blood level of pyruvate kinase (5.5 IU/g Hb) “(Table 1)”. DISCUSSION Erythrocytes (mature red blood cells) entirely depend on glucose as a source of energy. Glucose is usually catabolized to pyruvate and lactate in the Embeden-Meyerhof pathway, which is the major anaerobic glycolytic pathway. Pyruvate kinase catalyzes the conversion of phosphoenolpyruvate to pyruvate, resulting in the production of ATP, which is essential to provide energy to the erythrocytes. ATP plays a major role in maintaining a cation gradient in the erythrocyte, thus protecting the cell from premature death1,2,4,5 “(Figure 2)”. A deficiency of PK results in potassium leakage from the RBC membrane, thereby increasing its rigidity and accelerating RBCs destruction by the spleen leading to anemia, jaundice, hepatosplenomegaly, and reticulocytosis, all consequences of hemolysis1,2,4,5. Extravascular hemolysis, which is a common mode of red cell destruction in patients with PK deficiency leads to jaundice, bilirubin-rich gallstones. Hemosiderosis of parenchymal cells of the liver, pancreas, heart, and endocrine organs occurs with accumulating pigment1,2. Splenectomy in patients with hemolytic anemia increases hemoglobin by 1-3g/dl and reduces or even eliminates the requirement of blood transfusion. However, Splenectomy has been found to be an independent risk factor for the development of pulmonary hypertension. Splenectomy results in increased levels of senescent red cells. During hemolysis, Arginase 1 is released from red cells which catabolizes arginine to ornithine thereby reducing its availability for synthesis of endothelial Nitric Oxide (NO) and activation of coagulation system leading to pulmonary
vascular thrombosis7. Chou R et al reported a case of recurrent thromboembolic disease and chronic pulmonary hypertension in an adult patient with PK deficiency who underwent splenectomy as a child8. Considering these factors and since our patient already had pulmonary hypertension with severe Mitral stenosis, preoperative splenectomy was not advised Open heart surgery is rarely performed on patients with heart disease complicated by congenital hemolytic anemia with the aid of an artificial heart-lung machine. One of the major concern in open heart surgery for patients with PK deficiency is an accentuation of hemolysis with its consequences. Hemolysis is a fact in all extracorporeal circuits i.e. cardiopulmonary bypass, caused by exposure of blood to a non-endothelialized circuit and to mechanical shear stress. RBCs can be damaged on a sub lethal level resulting in altered rheological properties which leads to decreased micro perfusion leading to end organ dysfunction caused by cellular ischemia6. Hypothermia, by itself does not affect pyruvate kinase deficient RBCs but on CPB, hypothermia increases the viscosity of blood apart from increasing the systemic vascular resistance and thus exaggerating hemolysis. It is further magnified in the pediatric population as CPB circuit requires priming with stored blood secondary to the greater disparity between the circulating blood volume and the volume of the CPB circuit. Stored blood is more prone for hemolysis and contains reduced 2,3 DPG levels particularly with increased storage age. So preexisting hemolysis in patients with PK deficiency is further exaggerated by pump hemolysis which is directly proportional to the duration of extracorporeal circulation. To minimize hemolysis, a short CPB duration as was kept in our patient has been proved to be safe in presence of any congenital hemolytic anemia by Dal A and Kumar RS9.
Increased level of free RBCs together with an exhaust of their scavengers result in variety of serious clinical sequelae such as increased systemic and pulmonary vascular resistance, altered coagulation profile, platelet dysfunction, and renal tubular damage6. Also, excessive hemolysis with the release of free hemoglobin can exhaust haptoglobin and cause blockage of renal tubules leading to renal failure. A few studies have shown a correlation between hypothermia, rewarming, and generation of free radicals. Therefore, avoiding hypothermia during CPB may be helpful in such patients10. Studies documenting the rates of hemolysis for different pump types i.e. Standard roller pump, dynamically set roller pump, and centrifugal pump are conflicting. However, the rate of hemolysis is similar or lower with roller pump (nonocclusive) than those seen with the centrifugal pumps11. Intravascular hemolysis occurs often in patients with mechanical heart valve prostheses, mechanical trauma to the red cells and paraprosthetic regurgitation being the common causes. In most of the cases it is mild and subclinical. Nevertheless, hemolysis has also been described with Bio prosthetic valves which occurs due to structural deterioration leading to increase in turbulence, regurgitation causing alteration in the hemodynamic profile of the valve12. Also, due to shorter life (10years) due to structural failure requiring replacement compared to mechanical valves (>20years) and due to unavailability of size (<21) of Bio prosthetic valves, decision of implanting Mechanical valve with proven efficacy i.e. TTK Chitra was taken in our patient. Anticoagulant dose was adjusted to maintain INR between 2.5 to 3.5.
Hemolysis in the postoperative period can be assessed by 1. Measurement of blood counts (RBC, Hb, and hematocrit), haptoglobin, reticulocyte count and indirect bilirubin which shows the degree of hemolysis.
2 Renal function tests (blood urea, serum creatinine) assesses renal dysfunction which could be due to hemolysis. In summary, careful workup in the preoperative period and strategies to minimize hemolysis by avoiding hypothermia, limiting the aortic cross clamp time, total CPB time, maintaining good urine output and continuing same care in the post-operative period is central to the successful management of such type of cases.
Figure Legend List 1. Figure 1: Pre Op 2D Echo 2. Figure 2: Conversion of phosphoenolpyruvate to pyruvate by Pyruvate kinase
References 1. Lucie Luzzatto : Hemolytic anaemias and anaemia due to acute blood loss, in Kasper D.L (ed):
Harrison’s principles of internal medicine, 16th edition. USA, Mc graw hill, 2012, pp 877-
878. 2. Zanella A, Fermo E, Bianchi P, et al: Red cell pyruvate kinase deficiency: molecular and clinical aspects. British Journal of Haematology 130: 11-25,2005 3. Beutler E, Gelbart T: Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general white population. Blood 95(11):3585-3588, 2000 4. Wang C, Laurent R. Chiarelli L.R. et al: Human erythrocyte pyruvate kinase: characterization of the recombinant enzyme and a mutant form (R510Q) causing nonspherocytic hemolytic anemia. Blood 98: 3113-3120, 2001 5. Kedar P, Warang R, Colah B, et al: Red cell Pyruvate Kinase deficiency in neonatal jaundice cases in India. Indian Journal of Pediatrics 73:985-988, 2006; 6. Vercaemst L: Hemolysis in cardiac surgery patients undergoing cardiopulmonary bypass: a review in search of a treatment algorithm. J Extra Corpor Technol 40 (4): 257-67, 2008 7. Elizabeth SK, Gladwin MT: Hemolytic anemia associated Pulmonary artery Hypertension in Sickle cell disease and Thallesemia, in Jason X J Yuan (ed): Textbook of Pulmonary Vascular Disease,1stedition. UK, Springer, 2011, pp 1270 8. Chou R, De Loughery TG: Recurrent thromboembolic disease following splenectomy for pyruvate kinase deficiency. Am J Hematology. 67(3) Jul: 197-199, 2001 9. Dal A and Kumar RS: Open heart surgery in presence of hereditary spherocytosis. J Cardiovasc Surg 36: 447–448, 1995
10. Iyengar J, George A, Rissell JC, et al: Generation of Free Radicals During Cold Injury and Rewarming. Vasc Endovascular Surg 24: 467-74, 1990 11. Hansbro SD, Sharpe DA, Catchpole R, et al: Hemolysis during cardiopulmonary bypass: an in vivo comparison of standard roller pumps, nonocclusive roller pumps and centrifugal pumps. Perfusion 14(1): 3-10, 1999 12. Maraj R, Jacobs LE, Ioli A, et al: Evaluation of hemolysis in patients with prosthetic heart valves. Clin.Cardiol 21:387-392, 1998
Table 1
Perioperative Hb, Serum Bilirubin levels and Pyruvate Kinase level
Intervals
Pre-op
Just
Post
Postop
Postop
Postop
before
CPB
6 hrs
day 1
6 months
7.1
8.5
8.1
7.8
2.54
1.6
4.56
CPB Measured plasma Hb %
7.3
8.2
Sr Bilirubin
2.48
2.48
Pyruvate Kinase levels
6.9
(IU/g Hb)
5.5
PII: DOI: Reference:
S1053-0770(16)00308-6 http://dx.doi.org/10.1053/j.jvca.2016.03.146 YJCAN3628
To appear in: Journal of Cardiothoracic and Vascular Anesthesia Received date: 12 January 2016 Cite this article as: Shakuntala Basantwani, Balasaheb Govardhane, Shital Shinde and Bharati Tendolkar, Mitral Valve Replacement with Cardiopulmonary Bypass in Patient with Pyruvate Kinase Deficiency – A Case Report, Journal of Cardiothoracic and Vascular Anesthesia, http://dx.doi.org/10.1053/j.jvca.2016.03.146 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Mitral valve replacement with cardiopulmonary bypass in patient with Pyruvate kinase deficiency – A case report
Authors: Dr. Shakuntala Basantwani – Corresponding Author Mobile Number: +91-9819018461 Institution: Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai 400022 Email : [email protected]
Dr. Balasaheb Govardhane Dr. Shital Shinde Dr. Bharati Tendolkar
INTRODUCTION Red cell Pyruvate Kinase (PK) deficiency is the most common enzyme abnormality in the Embeden Meyerhof pathway of glycolysis in humans, first reported by Valentine et al in 1961. It is an inherited autosomal recessive metabolic disorder which affects the survival of red blood cell. It is caused by mutations in PKLR gene (Pyruvate kinase Liver and Red Blood Cells), The prevalence rate of heterozygous carriers of chromosome 1 deficient PK –LR gene is believed to be approximately 1%. Beutler and Gelbart estimated the incidence of PK deficiency in the United States to be 1:20,000. However, the incidence is much higher in remote and exclusive communities such as the Amish in Pennsylvania and Ohio and some communities in southern Utah.
1,2,3,4
. PK deficiency is not uncommon in India but the data on its prevalence in Indian
population is lacking. The clinical severity ranges from mildly compensated anemia to severe anemia of childhood and unconjugated hyperbilirubinemia requiring exchange transfusion5. Open-heart surgery for cardiac lesions (congenital or acquired), in patients with hematologic diseases, although infrequent, presents potential management problems during the perioperative period. Cardiopulmonary bypass (CPB) involves contact of blood with bypass circuit surfaces, hypothermia, hypo perfusion and reperfusion in which cell damage is likely to occur6. Application of CPB for patients with PK deficiency can result in fatal hematologic complications. The literature on patients with pyruvate kinase deficiency undergoing cardiac surgery is rare, therefore the authors wish to share their experience and strategy in the management of such patients. The patient’s parents were informed regarding our intention to publish the case and also agreed for his blood sample being sent for free hemoglobin analysis. Therapeutic and other diagnostic
procedures in this case did not change with respect to our standard guidelines, so local ethics committee approval was not required.
CASE REPORT A 7-year-old male child weighing 15kg was admitted to our hospital with rheumatic heart disease having severe mitral restenosis and history of jaundice with history of multiple blood transfusion for past 1 year. Child was previously diagnosed as a case of pyruvate kinase deficiency in a child care hospital where he was treated for RHD and jaundice prior to the admission. He also had undergone Balloon mitral valvotomy (BMV) 6 months back for severe mitral stenosis. Routine blood test showed Hemoglobin 7.3g%, anisopoikilocytosis, Total leucocyte count of 4200, Total bilirubin of 2.48 (D-0.98, I-1.5) (Table 1) with normal liver enzymes and renal function test. Ultrasonography revealed moderate hepatosplenomegaly. Blood level of Pyruvate kinase was 6.9 U/g Hb (normal value 9-13 U/g Hb) (Table 1). Normal reticulocyte counts and normal red cell osmotic fragility indicated the lack of active hemolysis. Preoperative 2 dimensional echocardiography revealed rheumatic heart disease with post (BMV), severe Mitral stenosis (Mitral valve area 0 .6 cm2), moderate Mitral regurgitation and moderate tricuspid regurgitation with severe pulmonary arterial hypertension (70 mmHg) and Right ventricle pressure overload pattern with Wilkin score 10 “(Figure 1)”. Child was receiving Digoxin and furosemide. In the preoperative period, anemia was corrected with one unit packed red cell and General anesthesia was induced with Injection Propofol and Rocuronium following premedication with midazolam and fentanyl and intubated with 5.5 cuffed endotracheal tube. Depth of anesthesia was maintained with infusions of rocuronium and Fentanyl, desflurane.
Median strenotomy was employed and CPB was initiated post heparinization with standard aortobicaval cannulation. Bypass circuit was primed with two units of fresh blood. Intermittent ante grade warm blood hyperkalemic cardioplegia was administered every 20 min to provide myocardial protection. Through a right atrial trans septal approach, mitral valve was replaced with TTK Chitra 19 Aortic valve in reverse position valve in view of small size annulus and tricuspid ring annuloplasty was performed. Normothermia (36°C) and mean arterial blood pressure around 70 mm Hg was maintained throughout the procedure. During the bypass period, urine output was maintained with the use of Mannitol 50 ml and furosemide 20 mg. Child was gradually weaned off from CPB with heart rate of 120/min and BP104/60 mm of Hg with ionotropic supports of dopamine 5ug/kg/min, adrenaline 0.2ug/kg/min, 0.3mg/kg /min and Epicardial pacing. Duration of CPB was 70 min and aortic cross clamp time was 52 mins. Immediately after coming off CPB, 1 unit of fresh frozen plasma and two units of platelets were transfused in view on inadequate hemostasis. Hemoglobinuria was not observed. Child was mechanically ventilated overnight and extubated next morning. The total volume of blood in the chest drainage system was 100ml in 24 hrs. One unit of packed cell transfusion was used to restore the hemoglobin level to 8.5. Postoperative analgesia was maintained with IV Paracetamol 15mg/kg and injection Tramadol 1mg/kg 8 hourly. In view of the uncertain tolerance of the abnormal red cells to cardiopulmonary bypass in PK deficiency, free plasma hemoglobin, liver and renal function tests, urine samples were reviewed on the first postoperative day and showed slight hemolysis in the form of elevated bilirubin in the blood sample and elevated bilirubin and urobilinogen in the urine with normal renal functions. The levels of these parameters slowly reduced during the next postoperative days and the patient
was discharged on the seventh postoperative day. However, at six months follow up, child was found to have anemia, jaundice and marked reduction in blood level of pyruvate kinase (5.5 IU/g Hb) “(Table 1)”. DISCUSSION Erythrocytes (mature red blood cells) entirely depend on glucose as a source of energy. Glucose is usually catabolized to pyruvate and lactate in the Embeden-Meyerhof pathway, which is the major anaerobic glycolytic pathway. Pyruvate kinase catalyzes the conversion of phosphoenolpyruvate to pyruvate, resulting in the production of ATP, which is essential to provide energy to the erythrocytes. ATP plays a major role in maintaining a cation gradient in the erythrocyte, thus protecting the cell from premature death1,2,4,5 “(Figure 2)”. A deficiency of PK results in potassium leakage from the RBC membrane, thereby increasing its rigidity and accelerating RBCs destruction by the spleen leading to anemia, jaundice, hepatosplenomegaly, and reticulocytosis, all consequences of hemolysis1,2,4,5. Extravascular hemolysis, which is a common mode of red cell destruction in patients with PK deficiency leads to jaundice, bilirubin-rich gallstones. Hemosiderosis of parenchymal cells of the liver, pancreas, heart, and endocrine organs occurs with accumulating pigment1,2. Splenectomy in patients with hemolytic anemia increases hemoglobin by 1-3g/dl and reduces or even eliminates the requirement of blood transfusion. However, Splenectomy has been found to be an independent risk factor for the development of pulmonary hypertension. Splenectomy results in increased levels of senescent red cells. During hemolysis, Arginase 1 is released from red cells which catabolizes arginine to ornithine thereby reducing its availability for synthesis of endothelial Nitric Oxide (NO) and activation of coagulation system leading to pulmonary
vascular thrombosis7. Chou R et al reported a case of recurrent thromboembolic disease and chronic pulmonary hypertension in an adult patient with PK deficiency who underwent splenectomy as a child8. Considering these factors and since our patient already had pulmonary hypertension with severe Mitral stenosis, preoperative splenectomy was not advised Open heart surgery is rarely performed on patients with heart disease complicated by congenital hemolytic anemia with the aid of an artificial heart-lung machine. One of the major concern in open heart surgery for patients with PK deficiency is an accentuation of hemolysis with its consequences. Hemolysis is a fact in all extracorporeal circuits i.e. cardiopulmonary bypass, caused by exposure of blood to a non-endothelialized circuit and to mechanical shear stress. RBCs can be damaged on a sub lethal level resulting in altered rheological properties which leads to decreased micro perfusion leading to end organ dysfunction caused by cellular ischemia6. Hypothermia, by itself does not affect pyruvate kinase deficient RBCs but on CPB, hypothermia increases the viscosity of blood apart from increasing the systemic vascular resistance and thus exaggerating hemolysis. It is further magnified in the pediatric population as CPB circuit requires priming with stored blood secondary to the greater disparity between the circulating blood volume and the volume of the CPB circuit. Stored blood is more prone for hemolysis and contains reduced 2,3 DPG levels particularly with increased storage age. So preexisting hemolysis in patients with PK deficiency is further exaggerated by pump hemolysis which is directly proportional to the duration of extracorporeal circulation. To minimize hemolysis, a short CPB duration as was kept in our patient has been proved to be safe in presence of any congenital hemolytic anemia by Dal A and Kumar RS9.
Increased level of free RBCs together with an exhaust of their scavengers result in variety of serious clinical sequelae such as increased systemic and pulmonary vascular resistance, altered coagulation profile, platelet dysfunction, and renal tubular damage6. Also, excessive hemolysis with the release of free hemoglobin can exhaust haptoglobin and cause blockage of renal tubules leading to renal failure. A few studies have shown a correlation between hypothermia, rewarming, and generation of free radicals. Therefore, avoiding hypothermia during CPB may be helpful in such patients10. Studies documenting the rates of hemolysis for different pump types i.e. Standard roller pump, dynamically set roller pump, and centrifugal pump are conflicting. However, the rate of hemolysis is similar or lower with roller pump (nonocclusive) than those seen with the centrifugal pumps11. Intravascular hemolysis occurs often in patients with mechanical heart valve prostheses, mechanical trauma to the red cells and paraprosthetic regurgitation being the common causes. In most of the cases it is mild and subclinical. Nevertheless, hemolysis has also been described with Bio prosthetic valves which occurs due to structural deterioration leading to increase in turbulence, regurgitation causing alteration in the hemodynamic profile of the valve12. Also, due to shorter life (10years) due to structural failure requiring replacement compared to mechanical valves (>20years) and due to unavailability of size (<21) of Bio prosthetic valves, decision of implanting Mechanical valve with proven efficacy i.e. TTK Chitra was taken in our patient. Anticoagulant dose was adjusted to maintain INR between 2.5 to 3.5.
Hemolysis in the postoperative period can be assessed by 1. Measurement of blood counts (RBC, Hb, and hematocrit), haptoglobin, reticulocyte count and indirect bilirubin which shows the degree of hemolysis.
2 Renal function tests (blood urea, serum creatinine) assesses renal dysfunction which could be due to hemolysis. In summary, careful workup in the preoperative period and strategies to minimize hemolysis by avoiding hypothermia, limiting the aortic cross clamp time, total CPB time, maintaining good urine output and continuing same care in the post-operative period is central to the successful management of such type of cases.
Figure Legend List 1. Figure 1: Pre Op 2D Echo 2. Figure 2: Conversion of phosphoenolpyruvate to pyruvate by Pyruvate kinase
References 1. Lucie Luzzatto : Hemolytic anaemias and anaemia due to acute blood loss, in Kasper D.L (ed):
Harrison’s principles of internal medicine, 16th edition. USA, Mc graw hill, 2012, pp 877-
878. 2. Zanella A, Fermo E, Bianchi P, et al: Red cell pyruvate kinase deficiency: molecular and clinical aspects. British Journal of Haematology 130: 11-25,2005 3. Beutler E, Gelbart T: Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general white population. Blood 95(11):3585-3588, 2000 4. Wang C, Laurent R. Chiarelli L.R. et al: Human erythrocyte pyruvate kinase: characterization of the recombinant enzyme and a mutant form (R510Q) causing nonspherocytic hemolytic anemia. Blood 98: 3113-3120, 2001 5. Kedar P, Warang R, Colah B, et al: Red cell Pyruvate Kinase deficiency in neonatal jaundice cases in India. Indian Journal of Pediatrics 73:985-988, 2006; 6. Vercaemst L: Hemolysis in cardiac surgery patients undergoing cardiopulmonary bypass: a review in search of a treatment algorithm. J Extra Corpor Technol 40 (4): 257-67, 2008 7. Elizabeth SK, Gladwin MT: Hemolytic anemia associated Pulmonary artery Hypertension in Sickle cell disease and Thallesemia, in Jason X J Yuan (ed): Textbook of Pulmonary Vascular Disease,1stedition. UK, Springer, 2011, pp 1270 8. Chou R, De Loughery TG: Recurrent thromboembolic disease following splenectomy for pyruvate kinase deficiency. Am J Hematology. 67(3) Jul: 197-199, 2001 9. Dal A and Kumar RS: Open heart surgery in presence of hereditary spherocytosis. J Cardiovasc Surg 36: 447–448, 1995
10. Iyengar J, George A, Rissell JC, et al: Generation of Free Radicals During Cold Injury and Rewarming. Vasc Endovascular Surg 24: 467-74, 1990 11. Hansbro SD, Sharpe DA, Catchpole R, et al: Hemolysis during cardiopulmonary bypass: an in vivo comparison of standard roller pumps, nonocclusive roller pumps and centrifugal pumps. Perfusion 14(1): 3-10, 1999 12. Maraj R, Jacobs LE, Ioli A, et al: Evaluation of hemolysis in patients with prosthetic heart valves. Clin.Cardiol 21:387-392, 1998
Table 1
Perioperative Hb, Serum Bilirubin levels and Pyruvate Kinase level
Intervals
Pre-op
Just
Post
Postop
Postop
Postop
before
CPB
6 hrs
day 1
6 months
7.1
8.5
8.1
7.8
2.54
1.6
4.56
CPB Measured plasma Hb %
7.3
8.2
Sr Bilirubin
2.48
2.48
Pyruvate Kinase levels
6.9
(IU/g Hb)
5.5