ORIGINAL ARTICLE
Splenectomy for Children With Thalassemia: Total or Partial Splenectomy, Open or Laparoscopic Splenectomy Ahmed H. Al-Salem, FRCI, FACS, FICS
Summary: Splenomegaly and hypersplenism are common complications among children with thalassemia necessitating splenectomy. Thirty-six children (27 b-thalassemia major, 3 Hb H disease, and 6 thalassemia intermediate) had total splenectomy (11 laparoscopic and 13 open splenectomy) or partial splenectomy (12 patients). In the partial splenectomy group, 2 with Hb H required no transfusions. For those with b-thalassemia major who had partial splenectomy (9 patients), there was a reduction in the number of transfusions from a preoperative mean of 15.2 transfusions per year to a postoperative mean of 8.2 transfusions per year. Subsequently and as a result of increase in the size of splenic remnant, their transfusions increased, but none required total splenectomy. Twenty-four patients had total splenectomy (13 open and 11 laparoscopic splenectomy). Their postsplenectomy transfusions decreased from a preoperative mean of 17.8 transfusions per year to a postoperative mean of 10 transfusions per year. There was no mortality, and none developed postoperative sepsis or thrombotic complications. Total splenectomy is beneficial for children with b-thalassemia major and hypersplenism by reducing their transfusion requirements. Laparoscopic splenectomy is however more beneficial. Partial splenectomy reduces their transfusion requirements, but only as a temporary measure, and so it is recommended for children younger than 5 years of age. Key Words: thalassemia, splenectomy, partial splenectomy, laparoscopic splenectomy
(J Pediatr Hematol Oncol 2016;38:1–4)
T
here are many types of thalassemia, but the most important affect either the a-chain or b-chain synthesis. The clinical picture of thalassemia varies widely, depending on the severity and age at diagnosis. They range from a mild, almost asymptomatic form to a severe and sometimes fatal form. In the homozygous state, b-thalassemia causes severe, transfusion-dependent anemia. In the heterozygous state, the b-thalassemia trait causes mild-to-moderate microcytic anemia. Today, regular blood transfusion combined with well-monitored chelation therapy has become the standard therapy and has drastically changed the outlook for these patients.1–3 The aim of the therapy is regular blood transfusion every 2 to 3 weeks to keep the hemoglobin (Hb) level over 10 g/dL and iron overload should be treated aggressively with chelators. This was made simpler with the development of oral chelators medications.4–6 As a result of this, the prognosis of these patients has improved markedly. This, however, is not the case in developing countries where Received for publication July 28, 2013; accepted January 14, 2016. From the Department of Pediatric Surgery, Maternity and Children Hospital, Dammam, Saudi Arabia. The author declares no conflict of interest. Reprints: Ahmed H. Al-Salem, FRCI, FACS, FICS, P.O. Box 61015, Qatif 31911, Saudi Arabia (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
regular blood transfusion is not readily available. Adding to this is the poor compliance of some of these patients, which ultimately leads to severe complications as a result of inadequate treatment. One of these complications is development of splenomegaly and hypersplenism necessitating splenectomy.7–10 Splenectomy, however, is associated with increased risk of thrombotic complications and overwhelming postsplenectomy sepsis and to overcome this a variety of procedures aiming at immunopreservation have been advocated including partial splenectomy.11–18 This is an analysis of our experience with total (open or laparoscopic) and partial splenectomy in the management of children with thalassemia.
PATIENTS AND METHODS Thirty-six children with thalassemia (27 b-thalassemia major, 3 Hb H disease, 6 thalassemia intermediate) who had total splenectomy (11 laparoscopic splenectomy and 13 open splenectomy) or partial splenectomy (12 patients) were studied retrospectively. Their records were reviewed for: age at operation, sex, immunization, operative procedures, operative time, spleen weight, hospital stay, postoperative complications, and outcome. In all, the indication for splenectomy was hypersplenism judged by the presence of splenomegaly and increased blood transfusions when the Hb drop exceeded 0.5 per week. All were vaccinated with pneumococcal, meningococcal, and Haemophilus influenzae vaccines. The results were compared in the 2 groups using preoperative and postoperative transfusion requirements based on Hb drop per week and the number of transfusions per year (each transfusion consisted of 250 to 300 mL of packed RBC). The open and the laparoscopic splenectomy groups were compared in terms of operative time, hospital stay, and postoperative recovery. In those who underwent partial splenectomy, about 90% to 95% of the size of the enlarged spleen was removed and the remaining segment was approximately one third of the normal spleen. Whether to preserve the lower pole of the spleen (9 patients) or upper pole (3 patients), was decided intraoperatively based on the distribution of polar vessels. The splenic remnant was fixed to the abdominal wall with interrupted sutures to avoid torsion. On follow-up, the function of the remaining spleen was evaluated using multiple estimation of complete blood count, Howell-Jolly bodies, immunoglobulins, abdominal ultrasound, and/or computed tomography scan and splenic isotope scan. Postoperatively, all patients were covered with oral penicillin for a minimum of 2 years depending on the patient’s age.
RESULTS Thirty-six children with thalassemia (27 b-thalassemia major, 3 Hb H disease, 6 thalassemia intermediate) had either total splenectomy (24 patients) or partial
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splenectomy (12 patients) as part of their management at our hospital. Of the total splenectomy group, 11 had laparoscopic splenectomy (4 thalassemia intermediate and 7 b-thalassemia major) and 13 had open splenectomy (2 thalassemia intermediate and 11 b-thalasemia intermediate). All the 3 children with Hb H disease had partial splenectomy (Table 1). Twelve children had partial splenectomy. The mean weight of the excised spleen was 358 g (range, 180 to 750 g). On follow-up ranging from 7 to 11 years (mean, 8.6 y), 2 patients with Hb H disease required no more blood transfusions. The transfusion requirement of the third patient with Hb H disease decreased from 15 transfusions per year to 10 transfusions per year (from 1.2 g per week Hb drop to 0.6 g per week). This drop persisted for 1 year after partial splenectomy, but his transfusion requirements subsequently increased. The increase in blood transfusion requirements correlated positively with increase in the size of splenic remnant, which was documented by ultrasound and computed tomography scan. This patient underwent total splenectomy 1½ years after partial splenectomy, following which his transfusion requirements decreased from 16 transfusions per year to 9 transfusions per year. For those with b-thalassemia major who had partial splenectomy, there was a reduction in the number of blood transfusions from a preoperative mean of 15.2 transfusions per year (range, 13 to 22 transfusions per year) to a postoperative mean of 8.2 transfusions per year (range, 2 to 11 transfusions per year). Their Hb drop per week decreased from a preoperative mean of 1.6 g per week (range, 0.8 to 3.5 g per week) to a postoperative mean of 0.5 g per week (range, 0.2 to 0.75 g per week). This was the case during the first 1 to 2 years after partial splenectomy wherein some of them required only 2 to 3 transfusions per year. However, subsequently, and as a result of increase in the size of splenic remnants, their transfusion requirements increased, but none of them so far required total splenectomy. Their mean postoperative transfusion requirements at present are 10.5 transfusions per year (range, 10 to 11.5 transfusions per year) and their mean postoperative Hb drop is 0.45 g/week (range, 0.4 to 0.58 g/wk). In all those who had partial splenectomy, the splenic remnants proved functional. There were no Howel-Jolly bodies, and their immunoglobulin M (IgM) levels did not change significantly. Their mean postoperative platelet count was 476,000 (range, 190,000 to 662,000). Six of them had isotope scan of the spleen, which showed increased splenic perfusion with average colloid tracer uptake. Twenty-four children (18 b-thalassemia major and 6 thalassemia intermediate) had total splenectomy (11 had laparoscopic splenectomy and 13 had open splenectomy).
One of them had splenectomy, left inguinal herniotomy, and circumcision at the same time. Their mean preoperative transfusion requirements were 17.8 transfusions per year (range, 12 to 23 transfusions per year) and their mean Hb drop was 1.8 g per week (range, 0.5 to 2.3 g per week). On follow-up, ranging from 5 to 11.5 years (mean, 6 y), 2 patients required no blood transfusions during the first 2 postoperative years and 1 required only single blood transfusion. Overall, they continued to receive blood transfusions but at a lower frequency. Their mean postsplenectomy transfusion requirements was 10 transfusions per year (range, 8 to 12 transfusions per year) and their mean Hb drop was 0.45 g/week (range, 0.3 to 0.65 g/wk). Their mean splenic weight was 747.5 g (range, 240 to 1093 g). A comparison of the transfusion requirements in the 2 groups is shown in Table 1. A comparison between the open and laparoscopic splenectomy groups showed a significant difference between the 2 groups regarding the operative time and hospital stay. Laparoscopic splenectomy took longer operative time. The mean operative time for laparoscopic splenectomy group was 2.5 hours (range, 1.5 to 3 h) when compared with 1.2 hours (range, 0.8 to 1.75 h for the open splenectomy group; P < 0.0001). The mean hospital stay was 4.2 days (range, 3 to 7 d) for the laparoscopic splenectomy group when compared with 6.5 days (range, 5 to 12 d) for the open splenectomy group (P < 0.0001). There was no mortality in our series, and none of our patients developed postoperative thrombotic or septic complications.
Volume 38, Number 1, January 2016
DISCUSSION Thalassemias are considered the most common hemoglobinopathy in the world and represent a major health problem. About 300 million people are carriers for the thalassemia gene Worldwide and about 15 million people have clinically apparent thalassemia. The prognosis of patients with thalassemia major is highly dependent on the patient’s adherence to long-term treatment programs, namely regular blood transfusion program and lifelong iron chelation.1,3 The introduction of chelating agents capable of removing excessive iron from the body has dramatically increased their life expectancy and recently the introduction of oral chelating agents has simplified their management.2,4–6 Regular blood transfusions combined with wellmonitored chelation therapy is now the standard therapy of patients with thalassemia. Although bone marrow transplantation offers cure for patients with thalassemia major, it is costly, not readily available, and not without complications.19,20
TABLE 1. Comparison of the Total Splenectomy and Partial Splenectomy Groups
Total Splenectomy (27 Patients) Open Splenectomy (13)
Laparoscopic Splenectomy Group (11 Patients)
*11 b-thalassemia major *7 b-thalassemia major *2 thalassemia intermediate *4 Thalassemia intermediate *11 males:2 females *6 males:5 females Mean age: 7.8 y (range: 4.5-12 y) *Mean age: 6.8 y (range: 4-11 y) *Mean preoperative transfusion requirements/year (range): 17.2 (12-23) *Mean preoperative Hb drop/week (range): 1.8 g/wk (0.5-2.3) *Mean postoperative transfusion requirements/year (range): 10 (8-12) *Mean postoperative Hb drop/week (range): 0.45 g/wk (0.3-0.65)
Partial Splenectomy Group (12 Patients) *9 b-thalassemia *3 Hb H disease *4 males:8 females *Mean age: 6.9 y (range: 3-10 y) 15.2 (11-22) 1.6 g/wk (0.8-3.5) 13 (11-15) 0.55 g/wk (0.4-0.85)
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Volume 38, Number 1, January 2016
Splenectomy for Thalassemia
However, the frequency of a- and b-thalassemia genes are variable worldwide and also in the different regions of Saudi Arabia. In the Eastern Province of Saudi Arabia, there is a high prevalence of hemoglobinopathies, mainly sickle cell anemia and thalassemia, and like other parts of Saudi Arabia, children with b-thalassemia major tend to have severe complications because of inadequate treatment.8,9,21–23 Adding to this is the poor compliance of these patients with regular blood transfusion and deferoxamine therapy, which ultimately leads to hemosiderosis and its related complications. The recently established hemoglobinopathies centers in different parts of Saudi Arabia where thalassemia is prevalent are expected to provide comprehensive management of these children, which ultimately will result in a decrease in both morbidity and mortality. The spleen is one of the common and early organs to be affected in children with thalassemia, and the degree of splenomegaly is related to the severity of thalassemia and compliance with regular blood transfusions. Splenomegaly in these patients can at times be massive necessitating splenectomy to overcome the frequently associated hypersplenism and also to relieve them from the mechanical pressure of the enlarged spleen.7,8,10 With the use of regular blood transfusion program, massive splenomegaly is unusual nowadays. Nevertheless, hypersplensim manifested by increased destruction of transfused RBC and increase transfusion requirements is still a very common complication of b-thalassemia major. This is specially so in developing countries where compliance is poor. However, splenectomy is associated with increased risk of thrombotic complications and postsplenectomy overwhelming infection (OPSI).24–26 It is also of importance to note that patients with thalassemia major are prone to develop infection more than normal children.27 The cell-mediated immunity is suppressed and neutrophil function is abnormal in these patients. The decision to perform splenectomy in children with thalassemia requires careful assessment; nevertheless, splenectomy may be beneficial to reduce their transfusion requirements with its associated risks. Several criteria are used to aid in the decision for splenectomy in these patients. We adopted a policy that splenectomy should be considered in those who require >200 to 250 mL/kg of PRBC per year to maintain an Hb level of 10 g/dL or a drop in their Hb level by >0.5 g/wk. To obviate the risks of postsplenectomy overwhelming infections, alternatives toward total splenectomy have been advocated. These include partial splenectomy, partial splenic dearterialization, partial splenic embolization, and splenectomy with splenic slice grafting.11–18 Twelve of our patients had partial splenectomy. Three of them had Hb H disease, 2 of them required no more blood transfusions, whereas the third continued to receive blood transfusions but at a lower frequency. Subsequently, and as a result of increase in the size of splenic remnant, his blood transfusion requirements increased necessitating total splenectomy 1.5 years after partial splenectomy. Although the number of patients with Hb H disease in our series is small to draw any conclusions from, we feel that partial splenectomy should be attempted first for children with Hb H disease and if relapse should occur, total splenectomy can be performed subsequently. In the remaining patients with b-thalassemia major, partial splenectomy resulted in a decrease in their transfusion requirements but this was temporary for the first 1 to 2 years after partial splenectomy. Subsequently, however, their transfusion requirements increased gradually but still less than their
prepartial splenectomy requirements. This increase in transfusion requirements correlated with increase in the size of splenic remnants, but none of them so far required total splenectomy. Therefore, for those with b-thalassemia major, partial splenectomy is beneficial in reducing their transfusion requirements but only as a temporary measure. We recommend partial splenectomy for children with bthalassemia major who were younger than 5 years of age, as they are at greatest risk of postsplenectomy sepsis, but if this proves to be ineffective subsequently, total splenectomy can be performed. Partial splenectomy is beneficial in these patients, not only it reduces their transfusion requirements, obviate the risk of post splenectomy sepsis, but the retained splenic remnant also provides a storage area for excessive iron load. The subsequent regrowth of the splenic remnant may necessitate total splenectomy. Patients with b-thalassemia major may require splenectomy to overcome hypersplenism. Splenectomy has long been shown to decrease their transfusion requirements, and so their iron overload. Adding to this is the fact that splenectomy eliminates the discomfort from the mechanical pressure of the enlarged spleen as well as increasing their growth rate. In those who had partial splenectomy, the splenic remnant proved functional. There was no evidence of postsplenectomy sepsis in any of them, no Howell-Jolly bodies, their IgM levels did not change ,and the splenic remnant proved functional on scintigraphy. With the recent advances in minimal invasive surgery, laparoscopic splenectomy has become the procedure of choice to treat children with various hematologic disorders, including those with b-thalassemia.28–31 Eleven of our patients had laparoscopic splenectomy and when compared with open splenectomy, laparoscopic splenectomy was found to be superior. Not only it reduces their transfusion requirements but it is superior with regard to duration of hospital stay, cosmetic appearance, and postoperative recovery. Laparoscopic splenectomy, however, may not be the ideal procedure for those with massive splenomegaly. Splenectomy, whether open or laparoscopic, is associated with an increased risk of sepsis. To minimize this risk, splenectomy should be delayed as much as possible until after 5 years of age when the risk of postsplenectomy sepsis decreases greatly; they should be immunized with pneumococcal, H. influenzae, and meningococcal vaccines; and they should receive prophylactic penicillin. All our patients received pneumococcal as well as meningococcal vaccines and H. influenzae vaccine. We routinely give our patients prophylactic penicillin for 2 to 3 years postsplenectomy depending on the age of the child, and we educate the parents to seek medical advice in any febrile illness.
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REFERENCES 1. Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2011;118:3479–3488. 2. Olivieri NF, Brittenham GM, McLaren CE, et al. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. N Engl J Med. 1998;339:417–423. 3. Taher AT, Musallam KM, Cappellini MD, et al. Optimal management of beta thalassaemia intermedia. Br J Haematol. 2011;152:512–523. 4. Neufeld EJ. Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood. 2006;107:3436–3441. 5. Vichinsky E. Clinical application of deferasirox: practical patient management. Am J Hematol. 2008;83:398–402.
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6. Taher A, El-Beshlawy A, Elalfy MS, et al. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with b-thalassaemia: the ESCALATOR study. Eur J Haematol. 2009;82:458–465. 7. Casale M, Cinque P, Ricchi P, et al. Effect of splenectomy on iron balance in patients with b-thalassaemia major: a long-term follow-up. Eur J Haematol. 2013;91:69–73. 8. Al Hawsawi ZM, Hummaida TI, Ismail GA. Splenecotmy in thalassemia major: experience at Madina Maternity and children’s hospital, Saudi Arabia. Ann Trop Paediatr. 2001;21: 155–158. 9. Nasserallah Z. Patients with beta thalassemia major. Saudi Med J. 1995;16:13–16. 10. Al-Salem AH, Nasserulla Z. Splenectomy for children with thalassemia. Int Surg. 2002;87:269–273. 11. Kheradpir MH, Albouyeh M. Partial splenectomy in the treatment of thalassemia major. Z Kinderchir. 1985;40:195–198. 12. Meral A, Sevinir B, Sadikoglu Y, et al. Partial splenic embolization in beta thalassemia major: a case report. Turk J Pediatr. 2000;42:76–79. 13. Stanley P, Shen TC. Partial embolization of the spleen in patients with thalassemia. J Vasc Interv Radial. 1995;1:137–142. 14. Banani SA. Partial dearterialization of the spleen in thalassemia major. J Pediatr Surg. 1998;33:449–453. 15. Sarkar PK, Bhattacharya DK, Sarkar D. Splenectomy and splenic slice grafting in the management of thalassemia. Pediatr Surg Int. 2001;17:369–372. 16. Banani SA, Bahador A. Management of thalassemia major by partial splenectomy. Pediatr Surg Int. 1994;9:350–352. 17. De Montalembert M, Girot R, Revillon Y, et al. Partial splenectomy in homozygous beta thalassaemia. Arch Dis Child. 1990;65:304–307. 18. Pinca A, Di Palma A, Soriani S, et al. Effectiveness of partial splenic embolization as treatment for hypersplenism in thalassaemia major. Eur J Haematol. 1992;49:49–52.
19. Sabloff M, Chandy M, Wang Z, et al. HLA-matched sibling bone marrow transplantation for b-thalassemia major. Blood. 2011;117:1745–1750. 20. Baronciani D, Elauroci N, Dini G, et al. Spreading and outcome of opoietic stem cell transplantation in beta thalassemia major. Data from EBMT registry. Bone Marrow Transplant. 2011;46:S67. 21. Laditan AA, El Agib MA, Al Naeem S, et al. B-thalassemia major: experience at King Fahd Hofuf Hospital, AL Hassa, Saudi Arabia. Ann Saudi Med. 1996;16:560–563. 22. Dammas AS, Adedoying MA, Cheriya A. Experience with thalassemia major in Al Baha. Ann Saudi Med. 1995;15:589–593. 23. ElHazmi MAF. Haemoglobinopathies, thalassemia and enzymopathies in Saudi Arabia. Saudi Med J. 1992;13:488–499. 24. Shaw JF, Print CG. Post-Splenecotmy sepsis. Br J Surg. 1989; 76:1074–1081. 25. Lynch AM, Kapila R. Overwhelming postsplenectomy infection. Infect Dis Clin North Am. 1996;4:693–707. 26. Waghorn DJ. Overwhelming infection in asplenic patients: current best practice preventive measures are not being followed. J Clin Pathol. 2001;54:214–218. 27. Vento S, Cainelli F, Cesario F. Infections and thalassaemia. Lancet Infect Dis. 2006;6:226–233. 28. Laopodis V, Kritikos E, Rizzoti L, et al. Laparoscopic splenectomy in beta thalassemia major patients. Advantages and disadvantages. Surg Endosc. 1998;12:944–947. 29. Esposito C, Corcione F, Garipoli V, et al. Pediatric laparoscopic splenectomy: are there real advantages in comparison with the traditional open approach? Pediatr Surg Int. 1997;12:509–510. 30. Patel NM, Tantia O, Sasmal PK, et al. Laparoscopic splenectomy in patients of b thalassemia: our experience. J Minim Access Surg. 2010;6:70–75. 31. Konstadoulakis MM, Lagoudianakis E, Antonakis PT, et al. Laparoscopic versus open splenectomy in patients with beta thalassemia major. J Laparoendosc Adv Surg Tech A. 2006;16:5–8.
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Splenectomy for Children With Thalassemia: Total or Partial Splenectomy, Open or Laparoscopic Splenectomy Ahmed H. Al-Salem, FRCI, FACS, FICS
Summary: Splenomegaly and hypersplenism are common complications among children with thalassemia necessitating splenectomy. Thirty-six children (27 b-thalassemia major, 3 Hb H disease, and 6 thalassemia intermediate) had total splenectomy (11 laparoscopic and 13 open splenectomy) or partial splenectomy (12 patients). In the partial splenectomy group, 2 with Hb H required no transfusions. For those with b-thalassemia major who had partial splenectomy (9 patients), there was a reduction in the number of transfusions from a preoperative mean of 15.2 transfusions per year to a postoperative mean of 8.2 transfusions per year. Subsequently and as a result of increase in the size of splenic remnant, their transfusions increased, but none required total splenectomy. Twenty-four patients had total splenectomy (13 open and 11 laparoscopic splenectomy). Their postsplenectomy transfusions decreased from a preoperative mean of 17.8 transfusions per year to a postoperative mean of 10 transfusions per year. There was no mortality, and none developed postoperative sepsis or thrombotic complications. Total splenectomy is beneficial for children with b-thalassemia major and hypersplenism by reducing their transfusion requirements. Laparoscopic splenectomy is however more beneficial. Partial splenectomy reduces their transfusion requirements, but only as a temporary measure, and so it is recommended for children younger than 5 years of age. Key Words: thalassemia, splenectomy, partial splenectomy, laparoscopic splenectomy
(J Pediatr Hematol Oncol 2016;38:1–4)
T
here are many types of thalassemia, but the most important affect either the a-chain or b-chain synthesis. The clinical picture of thalassemia varies widely, depending on the severity and age at diagnosis. They range from a mild, almost asymptomatic form to a severe and sometimes fatal form. In the homozygous state, b-thalassemia causes severe, transfusion-dependent anemia. In the heterozygous state, the b-thalassemia trait causes mild-to-moderate microcytic anemia. Today, regular blood transfusion combined with well-monitored chelation therapy has become the standard therapy and has drastically changed the outlook for these patients.1–3 The aim of the therapy is regular blood transfusion every 2 to 3 weeks to keep the hemoglobin (Hb) level over 10 g/dL and iron overload should be treated aggressively with chelators. This was made simpler with the development of oral chelators medications.4–6 As a result of this, the prognosis of these patients has improved markedly. This, however, is not the case in developing countries where Received for publication July 28, 2013; accepted January 14, 2016. From the Department of Pediatric Surgery, Maternity and Children Hospital, Dammam, Saudi Arabia. The author declares no conflict of interest. Reprints: Ahmed H. Al-Salem, FRCI, FACS, FICS, P.O. Box 61015, Qatif 31911, Saudi Arabia (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
regular blood transfusion is not readily available. Adding to this is the poor compliance of some of these patients, which ultimately leads to severe complications as a result of inadequate treatment. One of these complications is development of splenomegaly and hypersplenism necessitating splenectomy.7–10 Splenectomy, however, is associated with increased risk of thrombotic complications and overwhelming postsplenectomy sepsis and to overcome this a variety of procedures aiming at immunopreservation have been advocated including partial splenectomy.11–18 This is an analysis of our experience with total (open or laparoscopic) and partial splenectomy in the management of children with thalassemia.
PATIENTS AND METHODS Thirty-six children with thalassemia (27 b-thalassemia major, 3 Hb H disease, 6 thalassemia intermediate) who had total splenectomy (11 laparoscopic splenectomy and 13 open splenectomy) or partial splenectomy (12 patients) were studied retrospectively. Their records were reviewed for: age at operation, sex, immunization, operative procedures, operative time, spleen weight, hospital stay, postoperative complications, and outcome. In all, the indication for splenectomy was hypersplenism judged by the presence of splenomegaly and increased blood transfusions when the Hb drop exceeded 0.5 per week. All were vaccinated with pneumococcal, meningococcal, and Haemophilus influenzae vaccines. The results were compared in the 2 groups using preoperative and postoperative transfusion requirements based on Hb drop per week and the number of transfusions per year (each transfusion consisted of 250 to 300 mL of packed RBC). The open and the laparoscopic splenectomy groups were compared in terms of operative time, hospital stay, and postoperative recovery. In those who underwent partial splenectomy, about 90% to 95% of the size of the enlarged spleen was removed and the remaining segment was approximately one third of the normal spleen. Whether to preserve the lower pole of the spleen (9 patients) or upper pole (3 patients), was decided intraoperatively based on the distribution of polar vessels. The splenic remnant was fixed to the abdominal wall with interrupted sutures to avoid torsion. On follow-up, the function of the remaining spleen was evaluated using multiple estimation of complete blood count, Howell-Jolly bodies, immunoglobulins, abdominal ultrasound, and/or computed tomography scan and splenic isotope scan. Postoperatively, all patients were covered with oral penicillin for a minimum of 2 years depending on the patient’s age.
RESULTS Thirty-six children with thalassemia (27 b-thalassemia major, 3 Hb H disease, 6 thalassemia intermediate) had either total splenectomy (24 patients) or partial
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splenectomy (12 patients) as part of their management at our hospital. Of the total splenectomy group, 11 had laparoscopic splenectomy (4 thalassemia intermediate and 7 b-thalassemia major) and 13 had open splenectomy (2 thalassemia intermediate and 11 b-thalasemia intermediate). All the 3 children with Hb H disease had partial splenectomy (Table 1). Twelve children had partial splenectomy. The mean weight of the excised spleen was 358 g (range, 180 to 750 g). On follow-up ranging from 7 to 11 years (mean, 8.6 y), 2 patients with Hb H disease required no more blood transfusions. The transfusion requirement of the third patient with Hb H disease decreased from 15 transfusions per year to 10 transfusions per year (from 1.2 g per week Hb drop to 0.6 g per week). This drop persisted for 1 year after partial splenectomy, but his transfusion requirements subsequently increased. The increase in blood transfusion requirements correlated positively with increase in the size of splenic remnant, which was documented by ultrasound and computed tomography scan. This patient underwent total splenectomy 1½ years after partial splenectomy, following which his transfusion requirements decreased from 16 transfusions per year to 9 transfusions per year. For those with b-thalassemia major who had partial splenectomy, there was a reduction in the number of blood transfusions from a preoperative mean of 15.2 transfusions per year (range, 13 to 22 transfusions per year) to a postoperative mean of 8.2 transfusions per year (range, 2 to 11 transfusions per year). Their Hb drop per week decreased from a preoperative mean of 1.6 g per week (range, 0.8 to 3.5 g per week) to a postoperative mean of 0.5 g per week (range, 0.2 to 0.75 g per week). This was the case during the first 1 to 2 years after partial splenectomy wherein some of them required only 2 to 3 transfusions per year. However, subsequently, and as a result of increase in the size of splenic remnants, their transfusion requirements increased, but none of them so far required total splenectomy. Their mean postoperative transfusion requirements at present are 10.5 transfusions per year (range, 10 to 11.5 transfusions per year) and their mean postoperative Hb drop is 0.45 g/week (range, 0.4 to 0.58 g/wk). In all those who had partial splenectomy, the splenic remnants proved functional. There were no Howel-Jolly bodies, and their immunoglobulin M (IgM) levels did not change significantly. Their mean postoperative platelet count was 476,000 (range, 190,000 to 662,000). Six of them had isotope scan of the spleen, which showed increased splenic perfusion with average colloid tracer uptake. Twenty-four children (18 b-thalassemia major and 6 thalassemia intermediate) had total splenectomy (11 had laparoscopic splenectomy and 13 had open splenectomy).
One of them had splenectomy, left inguinal herniotomy, and circumcision at the same time. Their mean preoperative transfusion requirements were 17.8 transfusions per year (range, 12 to 23 transfusions per year) and their mean Hb drop was 1.8 g per week (range, 0.5 to 2.3 g per week). On follow-up, ranging from 5 to 11.5 years (mean, 6 y), 2 patients required no blood transfusions during the first 2 postoperative years and 1 required only single blood transfusion. Overall, they continued to receive blood transfusions but at a lower frequency. Their mean postsplenectomy transfusion requirements was 10 transfusions per year (range, 8 to 12 transfusions per year) and their mean Hb drop was 0.45 g/week (range, 0.3 to 0.65 g/wk). Their mean splenic weight was 747.5 g (range, 240 to 1093 g). A comparison of the transfusion requirements in the 2 groups is shown in Table 1. A comparison between the open and laparoscopic splenectomy groups showed a significant difference between the 2 groups regarding the operative time and hospital stay. Laparoscopic splenectomy took longer operative time. The mean operative time for laparoscopic splenectomy group was 2.5 hours (range, 1.5 to 3 h) when compared with 1.2 hours (range, 0.8 to 1.75 h for the open splenectomy group; P < 0.0001). The mean hospital stay was 4.2 days (range, 3 to 7 d) for the laparoscopic splenectomy group when compared with 6.5 days (range, 5 to 12 d) for the open splenectomy group (P < 0.0001). There was no mortality in our series, and none of our patients developed postoperative thrombotic or septic complications.
Volume 38, Number 1, January 2016
DISCUSSION Thalassemias are considered the most common hemoglobinopathy in the world and represent a major health problem. About 300 million people are carriers for the thalassemia gene Worldwide and about 15 million people have clinically apparent thalassemia. The prognosis of patients with thalassemia major is highly dependent on the patient’s adherence to long-term treatment programs, namely regular blood transfusion program and lifelong iron chelation.1,3 The introduction of chelating agents capable of removing excessive iron from the body has dramatically increased their life expectancy and recently the introduction of oral chelating agents has simplified their management.2,4–6 Regular blood transfusions combined with wellmonitored chelation therapy is now the standard therapy of patients with thalassemia. Although bone marrow transplantation offers cure for patients with thalassemia major, it is costly, not readily available, and not without complications.19,20
TABLE 1. Comparison of the Total Splenectomy and Partial Splenectomy Groups
Total Splenectomy (27 Patients) Open Splenectomy (13)
Laparoscopic Splenectomy Group (11 Patients)
*11 b-thalassemia major *7 b-thalassemia major *2 thalassemia intermediate *4 Thalassemia intermediate *11 males:2 females *6 males:5 females Mean age: 7.8 y (range: 4.5-12 y) *Mean age: 6.8 y (range: 4-11 y) *Mean preoperative transfusion requirements/year (range): 17.2 (12-23) *Mean preoperative Hb drop/week (range): 1.8 g/wk (0.5-2.3) *Mean postoperative transfusion requirements/year (range): 10 (8-12) *Mean postoperative Hb drop/week (range): 0.45 g/wk (0.3-0.65)
Partial Splenectomy Group (12 Patients) *9 b-thalassemia *3 Hb H disease *4 males:8 females *Mean age: 6.9 y (range: 3-10 y) 15.2 (11-22) 1.6 g/wk (0.8-3.5) 13 (11-15) 0.55 g/wk (0.4-0.85)
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J Pediatr Hematol Oncol
Volume 38, Number 1, January 2016
Splenectomy for Thalassemia
However, the frequency of a- and b-thalassemia genes are variable worldwide and also in the different regions of Saudi Arabia. In the Eastern Province of Saudi Arabia, there is a high prevalence of hemoglobinopathies, mainly sickle cell anemia and thalassemia, and like other parts of Saudi Arabia, children with b-thalassemia major tend to have severe complications because of inadequate treatment.8,9,21–23 Adding to this is the poor compliance of these patients with regular blood transfusion and deferoxamine therapy, which ultimately leads to hemosiderosis and its related complications. The recently established hemoglobinopathies centers in different parts of Saudi Arabia where thalassemia is prevalent are expected to provide comprehensive management of these children, which ultimately will result in a decrease in both morbidity and mortality. The spleen is one of the common and early organs to be affected in children with thalassemia, and the degree of splenomegaly is related to the severity of thalassemia and compliance with regular blood transfusions. Splenomegaly in these patients can at times be massive necessitating splenectomy to overcome the frequently associated hypersplenism and also to relieve them from the mechanical pressure of the enlarged spleen.7,8,10 With the use of regular blood transfusion program, massive splenomegaly is unusual nowadays. Nevertheless, hypersplensim manifested by increased destruction of transfused RBC and increase transfusion requirements is still a very common complication of b-thalassemia major. This is specially so in developing countries where compliance is poor. However, splenectomy is associated with increased risk of thrombotic complications and postsplenectomy overwhelming infection (OPSI).24–26 It is also of importance to note that patients with thalassemia major are prone to develop infection more than normal children.27 The cell-mediated immunity is suppressed and neutrophil function is abnormal in these patients. The decision to perform splenectomy in children with thalassemia requires careful assessment; nevertheless, splenectomy may be beneficial to reduce their transfusion requirements with its associated risks. Several criteria are used to aid in the decision for splenectomy in these patients. We adopted a policy that splenectomy should be considered in those who require >200 to 250 mL/kg of PRBC per year to maintain an Hb level of 10 g/dL or a drop in their Hb level by >0.5 g/wk. To obviate the risks of postsplenectomy overwhelming infections, alternatives toward total splenectomy have been advocated. These include partial splenectomy, partial splenic dearterialization, partial splenic embolization, and splenectomy with splenic slice grafting.11–18 Twelve of our patients had partial splenectomy. Three of them had Hb H disease, 2 of them required no more blood transfusions, whereas the third continued to receive blood transfusions but at a lower frequency. Subsequently, and as a result of increase in the size of splenic remnant, his blood transfusion requirements increased necessitating total splenectomy 1.5 years after partial splenectomy. Although the number of patients with Hb H disease in our series is small to draw any conclusions from, we feel that partial splenectomy should be attempted first for children with Hb H disease and if relapse should occur, total splenectomy can be performed subsequently. In the remaining patients with b-thalassemia major, partial splenectomy resulted in a decrease in their transfusion requirements but this was temporary for the first 1 to 2 years after partial splenectomy. Subsequently, however, their transfusion requirements increased gradually but still less than their
prepartial splenectomy requirements. This increase in transfusion requirements correlated with increase in the size of splenic remnants, but none of them so far required total splenectomy. Therefore, for those with b-thalassemia major, partial splenectomy is beneficial in reducing their transfusion requirements but only as a temporary measure. We recommend partial splenectomy for children with bthalassemia major who were younger than 5 years of age, as they are at greatest risk of postsplenectomy sepsis, but if this proves to be ineffective subsequently, total splenectomy can be performed. Partial splenectomy is beneficial in these patients, not only it reduces their transfusion requirements, obviate the risk of post splenectomy sepsis, but the retained splenic remnant also provides a storage area for excessive iron load. The subsequent regrowth of the splenic remnant may necessitate total splenectomy. Patients with b-thalassemia major may require splenectomy to overcome hypersplenism. Splenectomy has long been shown to decrease their transfusion requirements, and so their iron overload. Adding to this is the fact that splenectomy eliminates the discomfort from the mechanical pressure of the enlarged spleen as well as increasing their growth rate. In those who had partial splenectomy, the splenic remnant proved functional. There was no evidence of postsplenectomy sepsis in any of them, no Howell-Jolly bodies, their IgM levels did not change ,and the splenic remnant proved functional on scintigraphy. With the recent advances in minimal invasive surgery, laparoscopic splenectomy has become the procedure of choice to treat children with various hematologic disorders, including those with b-thalassemia.28–31 Eleven of our patients had laparoscopic splenectomy and when compared with open splenectomy, laparoscopic splenectomy was found to be superior. Not only it reduces their transfusion requirements but it is superior with regard to duration of hospital stay, cosmetic appearance, and postoperative recovery. Laparoscopic splenectomy, however, may not be the ideal procedure for those with massive splenomegaly. Splenectomy, whether open or laparoscopic, is associated with an increased risk of sepsis. To minimize this risk, splenectomy should be delayed as much as possible until after 5 years of age when the risk of postsplenectomy sepsis decreases greatly; they should be immunized with pneumococcal, H. influenzae, and meningococcal vaccines; and they should receive prophylactic penicillin. All our patients received pneumococcal as well as meningococcal vaccines and H. influenzae vaccine. We routinely give our patients prophylactic penicillin for 2 to 3 years postsplenectomy depending on the age of the child, and we educate the parents to seek medical advice in any febrile illness.
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6. Taher A, El-Beshlawy A, Elalfy MS, et al. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with b-thalassaemia: the ESCALATOR study. Eur J Haematol. 2009;82:458–465. 7. Casale M, Cinque P, Ricchi P, et al. Effect of splenectomy on iron balance in patients with b-thalassaemia major: a long-term follow-up. Eur J Haematol. 2013;91:69–73. 8. Al Hawsawi ZM, Hummaida TI, Ismail GA. Splenecotmy in thalassemia major: experience at Madina Maternity and children’s hospital, Saudi Arabia. Ann Trop Paediatr. 2001;21: 155–158. 9. Nasserallah Z. Patients with beta thalassemia major. Saudi Med J. 1995;16:13–16. 10. Al-Salem AH, Nasserulla Z. Splenectomy for children with thalassemia. Int Surg. 2002;87:269–273. 11. Kheradpir MH, Albouyeh M. Partial splenectomy in the treatment of thalassemia major. Z Kinderchir. 1985;40:195–198. 12. Meral A, Sevinir B, Sadikoglu Y, et al. Partial splenic embolization in beta thalassemia major: a case report. Turk J Pediatr. 2000;42:76–79. 13. Stanley P, Shen TC. Partial embolization of the spleen in patients with thalassemia. J Vasc Interv Radial. 1995;1:137–142. 14. Banani SA. Partial dearterialization of the spleen in thalassemia major. J Pediatr Surg. 1998;33:449–453. 15. Sarkar PK, Bhattacharya DK, Sarkar D. Splenectomy and splenic slice grafting in the management of thalassemia. Pediatr Surg Int. 2001;17:369–372. 16. Banani SA, Bahador A. Management of thalassemia major by partial splenectomy. Pediatr Surg Int. 1994;9:350–352. 17. De Montalembert M, Girot R, Revillon Y, et al. Partial splenectomy in homozygous beta thalassaemia. Arch Dis Child. 1990;65:304–307. 18. Pinca A, Di Palma A, Soriani S, et al. Effectiveness of partial splenic embolization as treatment for hypersplenism in thalassaemia major. Eur J Haematol. 1992;49:49–52.
19. Sabloff M, Chandy M, Wang Z, et al. HLA-matched sibling bone marrow transplantation for b-thalassemia major. Blood. 2011;117:1745–1750. 20. Baronciani D, Elauroci N, Dini G, et al. Spreading and outcome of opoietic stem cell transplantation in beta thalassemia major. Data from EBMT registry. Bone Marrow Transplant. 2011;46:S67. 21. Laditan AA, El Agib MA, Al Naeem S, et al. B-thalassemia major: experience at King Fahd Hofuf Hospital, AL Hassa, Saudi Arabia. Ann Saudi Med. 1996;16:560–563. 22. Dammas AS, Adedoying MA, Cheriya A. Experience with thalassemia major in Al Baha. Ann Saudi Med. 1995;15:589–593. 23. ElHazmi MAF. Haemoglobinopathies, thalassemia and enzymopathies in Saudi Arabia. Saudi Med J. 1992;13:488–499. 24. Shaw JF, Print CG. Post-Splenecotmy sepsis. Br J Surg. 1989; 76:1074–1081. 25. Lynch AM, Kapila R. Overwhelming postsplenectomy infection. Infect Dis Clin North Am. 1996;4:693–707. 26. Waghorn DJ. Overwhelming infection in asplenic patients: current best practice preventive measures are not being followed. J Clin Pathol. 2001;54:214–218. 27. Vento S, Cainelli F, Cesario F. Infections and thalassaemia. Lancet Infect Dis. 2006;6:226–233. 28. Laopodis V, Kritikos E, Rizzoti L, et al. Laparoscopic splenectomy in beta thalassemia major patients. Advantages and disadvantages. Surg Endosc. 1998;12:944–947. 29. Esposito C, Corcione F, Garipoli V, et al. Pediatric laparoscopic splenectomy: are there real advantages in comparison with the traditional open approach? Pediatr Surg Int. 1997;12:509–510. 30. Patel NM, Tantia O, Sasmal PK, et al. Laparoscopic splenectomy in patients of b thalassemia: our experience. J Minim Access Surg. 2010;6:70–75. 31. Konstadoulakis MM, Lagoudianakis E, Antonakis PT, et al. Laparoscopic versus open splenectomy in patients with beta thalassemia major. J Laparoendosc Adv Surg Tech A. 2006;16:5–8.
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