Oliveira MC, Fernandes RA, Rodrigues CL, Ribeiro DA, Giovanardi MF, Viana MB and during early adult life. However, depending on the severity of hemolysis, the disorder may be diagnosed at any age.(14) About 75% of cases have a family history of HS.(1) In this study only 57% had a positive family history but this feature was not mentioned in the medical files of 5 patients. Regarding the clinical features, patients have varying degrees of anemia and jaundice and most children have mild to moderate enlargement of the spleen. Around two thirds of these cases were anemic, 70% had varying degrees of splenomegaly and 38% were jaundiced at presentation. The clinical feature is very heterogeneous ranging from asymptomatic to hydrops fetalis or stillbirth.(15,16) The clinical expression is relatively uniform within a given family but can vary considerably between families. In the present study, asymptomatic HS was diagnosed in three fathers and three mothers. The phenotypic variability of only one family was not uniform in its clinical presentation. In this family, the index case was classified as severe, transfusion- dependent, while his two siblings were classified as having mild disease. It has been estimated that 20% of HS patients have mild disease with compensated hemolysis. Moderate HS represents the largest group of patients comprising about 70% of cases, while a small group of patients, 3-5%, have a severe form and require regular transfusions.(17) In the present study most patients were classified as moderate, but a fifth was classified as having a severe phenotype. These patients were younger and needed blood transfusions more frequently than patients with mild and moderate disease. In a series of 468 Italian children with HS, only 7% were classified as severe, while 21% were mild and 72% moderate.(18) A small proportion of patients with a severe degree was also found in another study of 44 patients; only 2% had severe HS.(19) The higher proportion of patients with severe HS found in the current study may be attributed to the fact that classification was retrospective, without a true knowledge of the clinical situation of the patient at diagnosis. It is known that, ideally, patients should be classified when clinically stable because a simple viral infection may lead to a severe transient anemia and so the severity of HS may be overestimated.(12) Furthermore, we were not able to assess the three laboratory variables – Hb, bilirubin, and reticulocyte count – for all patients, which may affect proper allocation of patients to risk groups. The formation of bilirubin gallstones is one of the commonest complications in HS;(20) 6 to 50% of patients eventually develop symptomatic gallbladder disease at 10 to 30 years old and undergo cholecystectomy.(12,21,22) However, only 5 to 8% of children younger than ten have detectable gallstones.(18) In other words, the mean age at diagnosis of cholelithiasis is inversely proportional to the severity of the disease.(19) In the current series 27% of patients had gallstones, with the average age at diagnosis being 10 years old. Although it was possible to identify a tendency that the more severe forms of the disease are 12 associated with a higher incidence of gallstones, the difference was not statistically significant. Possibly the relatively small number of patients with gallstones in this sample can explain this finding. Other complications that occurred during the follow- up of these patients were acute spleen sequestration and aplastic crisis. Splenic sequestration was responsible for approximately 41% of indications for splenectomy. This finding supports results of the study of Rice et al.(23) in which 50% of splenectomies were indicated due to sequestration crises. Aplastic crises are generally less common and almost always following virally-induced bone marrow suppression. The most common causative agent is parvovirus B19, which confers life-long immunity.(24) As parvovirus serology was not available in this study, the etiology of aplastic crises could not be identified. Splenectomy is generally indicated in patients with HS to alleviate symptoms related to hemolysis.(25) Previously, splenectomy was considered a "routine procedure" in HS patients. Although the risk of overwhelming post- splenectomy sepsis can be reduced by the use of immunizations as well as postoperative antibiotic prophylaxis, its risk is never eliminated.(26) Moreover, concern about incomplete protection by pneumococcal vaccinations, emergence of penicillin-resistant pneumococci and poor compliance to antibiotic prophylaxis still persists. These factors contribute by increasing the risk of post-splenectomy infection.(3,26) Nowadays, splenectomy is reserved for patients with severe HS or those who develop complications such as symptomatic gallstones and transfusion-dependency.(27) The mean age at splenectomy has been reported to be from 6.6 to 13 years of age.(19,28,29) The proportion of splenectomized patients in the present study (35%) was quite similar to that reported by others (38.5%).(18) As previously stated, the main reason for referring patients to the tertiary Pediatric Hematological Center at Hospital of Clínicas of UFMG was anemia of unknown etiology, followed by anemia unresponsive to iron supplementation. It is important to highlight that during the interview at UFMG many children had positive family histories for HS or clear-cut symptoms of hemolytic anemia. It is surprising that the diagnosis of HS had not been considered by the general practitioner as a cause of gallstones and splenomegaly in children. The main limitation of this study is its retrospective design that results in limited control over the variables included in the analysis, especially regarding the classification of disease severity. In addition, molecular studies underlying the HS defect were not available and so its genetic distribution is not known. In conclusion, the clinical course of patients with HS in this series was relatively benign with cholelithiasis being a common complication. Despite the high proportion of splenectomized patients in the current study, most of them (65%) were not submitted to splenectomy which corroborates the literature that recommends trying to postpone and, when Rev Bras Hematol Hemoter. 2012;34(1):9-13