Long-Term Follow up of the Beneficial Effects and of Issues in Subtotal Splenectomy for Hereditary Spherocytosis

Total splenectomy is recommended in symptomatic cases of hereditary spherocytosis (HS) to reduce the severity of anemia but exposes patients to long-term infectious or thrombotic complications. Alternative strategies such as subtotal splenectomy (STS) have been developed, principally for children under the age of 6 with severe HS, who are not eligible to total splenectomy because of the high infectious risk and for older patients with mild HS complaining of chronic discomfort. Since our original report, several groups have shown that STS reduced the hemolytic rate, increased the red cell lifespan while maintaining an efficient splenic phagocytic function but the extent of follow-up has been limited. In order to define the long-term benefits of STS, we report here an update of our series that includes 90 patients who underwent STS at the Bicêtre hospital between 1985 and 2013, with a median-follow-up of 9.3 years (range 1-23 years). Two groups were defined on the basis of the disease phenotype: Group A included 42 patients for whom STS was performed because of severe/intermediate HS (transfusion requirement or hemoglobin (Hb) level <95 g/dL and Group B included 48 patients with a milder HS but presenting marked icterus, gallstones requiring cholecystectomy or chronic fatigue. At the time of STS, the mean hemoglobin level was 82 g/L in Group A vs. 110 g/L in Group B. Mean age at surgery was 7.6 ± 5.4 years (0.5-25 years), significantly lower in Group A than in Group B (4.3 vs. 10 years, p<0.0001). In all cases, STS was performed by laparotomy. Preoperative mean spleen volume was 513 ± 241% of normal. Surgery reduced by 88% the initial splenic volume. A functional assessment of the splenic remnant was performed by Howell jolly body counts and by splenic scintigraphy.  Splenic function was retained in 87 of 90 patients except for 3 individuals (2 post-operative necrosis of the remnant, 1 non-functional remnant). No severe infection or thrombotic event was documented during the entire period of follow-up. A sustainable hematological response was observed in 81 patients (90%) at the end of the evaluation period. The mean increase in the hemoglobin level was 27 g/L, with a hemoglobin level after STS being still higher in group B than in group A (130 ± 3.3g/L vs. 110 ± 3.3 g/L (p<0.0001). For the whole population, the mean number of transfusions per year and per patient was 0.097 after versus 1.7 before STS (for Group A only: 0.21 after vs. 3.65 before STS, p<0.0001). Of note, STS decreased the hemolytic rate but did not abrogate it: the reticulocyte count decreased from 399 ±195 G/L to 290 ±170 G/L (p<0.001), but the bilirubin level remained unchanged.  Seventeen patients (33%) developed cholelithiasis during the follow-up period. Gallstones were slightly more frequent in Group A than in Group B (47% vs. 15%, p=0.03). After an initial improvement, 8 patients (19% of patients from Group A) experienced a relapse with transfusion-dependant anemia and/or decrease of the hemoglobin level below 95g/L. Relapses occurred with a mean delay of 4.6 ± 1.2 years after STS. Assessing the remnant volume by ultrasonography and/or scintigraphy, we noticed that it increased quickly during the first year after STS but at a slower rate during the subsequent 5 years. The growth was faster in patients from Group A but there was no clear correlation at the end of the follow-up period between the hemoglobin level and the volume of the remnant. During the follow-up period twenty patients (22%) underwent total splenectomy with a mean delay of 8 ± 5.6 years after STS (range 0-20.1 years). Eight patients underwent total splenectomy for recurrence of anemia, the others for recurrent discomfort/pain of the remnant (n=7), icterus (n=3), wandering spleen (n=1) and early post-STS hemorrhage (n=1). Requirement for total splenectomy was significantly higher in Group A than Group B (40 of the patients vs. 6% at the last endpoint, p<0.0001).

In summary, our results show that in the long-term, STS resulted in a decrease in the hemolytic rate in HS. In children under the age of six years with severe HS, STS decreased the transfusion rate and increased the hemoglobin to a level compatible with normal growth while retaining splenic function. However, half of these patients will require total splenectomy, but at an age where it will be much safer. In milder HS, STS removed discomfort related to the high hemolytic rate whithout exposing the patients to the risks of a total splenectomy.