Long-term follow-up of subtotal splenectomy for hereditary spherocytosis: a single-center study

To the editor:

Red cells of patients with hereditary spherocytosis (HS) have a decreased surface-to-volume ratio,¹  leading to their trapping and destruction during their passage through the splenic cords.^2-4  Therefore, surgical total splenectomy (TS) by removing the main site of red cell destruction lengthens the red blood cell life span and, according to published guidelines, should be recommended in severe cases and needs to be considered in intermediate forms of HS.^5-8  However, spleen removal is associated with loss of important physiological functions: splenectomized patients are exposed to long-term complications including infectious risks (particularly high in children under 6 years of age⁹ ) and vascular risks.^10,11  To preserve the spleen function, subtotal splenectomy (STS) has been proposed as an alternative to TS. We and others published reports regarding a series of HS patients who underwent STS and showed that it reduced the hemolytic rate and increased the red cell life span while maintaining efficient splenic phagocytic function.^12-16  However, long-term results are still lacking.

We report here an update of our STS series which includes 79 patients from 71 families who underwent STS for HS at Bicêtre Hospital since February 1985 with at least 3 years’ follow-up. This represents the largest STS series in HS, with the longest follow-up to date (mean follow-up, 11 ± 0.7 years standard error of the mean [SEM]; range, 3-23 years). Patients’ characteristics are summarized in Table 1. Thirty-nine patients (group A) underwent STS for transfusion dependency (n = 31) and/or anemia with a baseline hemoglobin (Hb) level under 95 g/L (n = 8). For the 40 other patients (group B), all with a baseline Hb above 95 g/L, STS was performed for chronic fatigue (n = 18), mild asthenia with gallstones requiring cholecystectomy (n = 16) or with frank icterus (n = 6). The mean age at surgery was significantly lower in group A than in group B (4.3 vs 11 years, P < .0001). The procedure consisted of open surgical removal of 85% to 95% of the spleen, as previously described.^12,13  A cholecystectomy was performed when preoperative ultrasonography demonstrated stones in the gallbladder. The postsurgical complications were: 2 early hemorrhages, 1 late bowel occlusion, 2 patients with recurrent abdominal pain requiring completion, and 5 symptomatic wandering remnants requiring TS for 1 and fixation for the others. The phagocytic function of the spleen remnant was assessed using pitted red cell count, Howell-Jolly body count, and splenic scintigraphy performed at 1-year postsurgery and then every 5 years.¹⁷  A functional remnant spleen was documented following STS in 96% of the patients. Three patients were considered as asplenic: 1 showing a very small fixation (remnant length, 1 cm), the 2 others because of an early postsurgery necrosis. No severe infections (requiring hospitalization) or thrombotic event was noted during the follow-up period.

We confirmed the good hematologic response after STS as previously reported by our group^12,13  and others¹⁴  (Figure 1A). All patients but 1 experienced a significant increase in Hb level 1 year after surgery. The only primary failure was related to an insufficient removal of splenic tissue (postoperative remnant size: 208% of the volume of a normal spleen). The mean Hb level did not decrease over time, with a slight increase after 10 years of follow-up. At the last end point, a sustainable response (no symptom related to anemia and Hb level >95 g/L) was observed in 69 patients (87%). Fifty-nine patients had received at least 1 transfusion before STS. After STS, 65 patients (82%) remained free of any transfusion. In group A, the transfusion rate decreased from 3.13 to 0.19 transfusions per year per patient (P < .0001). However, as previously reported,^12,13  although STS decreased the hemolytic rate, it did not abrogate it. The bilirubin level remained unchanged, and among the 46 patients who did not undergo cholecystectomy at STS, 16 (35%) developed cholelithiasis during the follow-up. Fourteen underwent cholecystectomy with a mean delay of 7.5 years after STS. Gallstones were slightly more frequent in group A than in group B (43% vs 15%; P = .04).

Another concern is the growth of the remnant, consistently noted in previous STS reports.^13,14  The volume of the remnant was assessed using scintigraphy or, when not available, ultrasonography providing 3-dimensional measurements.^18-21  Surgery reduced by 88% the initial volume of the spleen. The remnant grew quickly during the first year, then at a slower rate until 5 years after surgery without reaching its presurgical volume (Figure 1B). Spleen growth was more pronounced in group A than in group B: at 5 years, remnant volume was found to be 5.5-fold the immediate postoperative volume in group A and 4.4-fold in group B, in the face of similar immediate postoperative volume in both groups. The growth was faster in patients with a hematologic relapse compared with the others (Figure 1C). For patients with a sustained hematologic response, we confirmed our initial report showing no clear correlation between the size of the remnant and the Hb level at the last follow-up (linear regression, R² 0.025, not significant). Twenty-one patients (27%) underwent TS with a mean delay of 8.4 ± 1.2 years after STS (range, 0-20.1 years). The TS rate was higher in group A than in group B (47% vs 8%, P < .0001). In all cases, TS was performed with no major surgical difficulties. One patient underwent early TS because of an immediate postoperative hemorrhage; 1 other for primary failure. Nine patients, all from group A, underwent TS for hematologic relapse when Hb level fell below 95 g/L, with relapses occurring with a mean delay of 5.3 ± 1 years after STS. The 10 other patients underwent TS for reasons not related to anemia: abdominal pain (n = 2), discomfort related to the remnant size (n = 5), major icterus (n = 2), or wandering spleen (n = 1). For these patients, TS was performed later after STS (11.3 ± 1.6 years; P = .02) (Figure 1D). This probably explains the higher rate of TS in our series in comparison with other reports with shorter follow-up. Of note, in group A, none of the preoperative characteristics (including the Hb levels, the spleen volume, or the transfusion rate) was found to be a reliable predictive parameter for future TS.

In summary, with the intrinsic limitations of a single-center retrospective study, our results clarify the improvement that can be expected from STS in HS on a long-term basis. Benefits of STS were different depending on the disease severity. In children under the age of 6 years with severe anemia and/or transfusion requirement, STS was very efficient and safe because it alleviates the transfusion rate and increases the Hb to a level compatible with normal growth and activity. Of interest, half of these patients will not require TS. However, the other half will require TS, but at an age when it will be much safer. In the case of patients with intermediate HS, splenectomy aims to remove discomfort related to the high hemolytic rate. For them, STS, by preserving the spleen functions, appears to be an interesting alternative; it avoids the distressing decision of TS abrogating hemolysis but carrying the long-term risk of infections and vascular events. However, the price to pay is the persistence of a lower but persistent hemolytic state that exposes patients to its own complications.