American Journal of Hematology 30:254-256 (1 989)

Long-Term Effect of Splenectomy on Transfusion Requirements in Thalassemia Major

Alan Cohen, Robin Gayer, and Jeannie Mizanin Division of Hematology, The Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School

of Medicine, Philadelphia

Splenectomy reduces transfusion requirements in the first year after surgery in patients with thalassemia major and hypersplenism. To determine whether this response is main- tained, we have studied transfusion requirements in 16 patients with thalassemia major for 2-17 years after splenectomy. Transfusion requirements remained stable (mean yearly change -0.1%) after the predictable fall in the first year after surgery. The mean change between the first postoperative year and the most recent year was -7 mllkg. Transfusion requirements and the magnitude of change from year to year were unrelated to the time since splenectomy. These studies indicate that the effect of splenectomy on transfusion requirements is long-lasting and that large variations in annual transfusion requirements after splenectomy should prompt a search for accessory spleens or other causes of red cell destruction.

Key words: thalassemia, hypersplenisrn, transfusion

INTRODUCTION

Patients with thalassemia major commonly develop hypersplenism after 5-10 years of regular red cell trans- fusions [ 11. As a result of splenic enlargement, transfu- sion requirements steadily increase, accelerating the in- f lux of toxic iron [2]. If splenectomy is performed when the transfusion requirement exceeds 200 ml/kg/yr, the transfusion requirement falls by 24-74% in the first year after surgery [ 31.

Disagreement exists as to whether the reduction in transfusion requirement is sustained beyond the first postsplenectomy year. Some investigators have found that the need for blood subsequently returns to presple- nectomy levels in the majority of patients [4], while other investigators have found that the reduction in trans- fusion requirement remains unchanged [2,5]. An accu- rate prediction of the long-term effect of splenectomy in thalassemia major is particularly important because the primary goal of surgery is to achieve or enhance negative iron balance in patients receiving iron chelation therapy. If the fall in transfusion requirements is short-lived, the impact of splenectomy on the prevention of iron overload will be diminished or lost. In the current study, we have evaluated transfusion requirements as long as 17 years

after splenectomy to determine whether or not the ben- eficial effects of splenectomy are long-lasting.

PATIENTS AND METHODS

Sixteen patients with Po and P' thalassemia major who receive regular red cell transfusions to maintain the pretransfusion hemoglobin level between 8.5 and 10.0 g/dl (85-100 g/L) were studied. The patients underwent splenectomy at 2-3 1 years of age and are currently 8-34 years old. The interval since splenectomy is 2-17 years; 98 patient-years are included in the study.

Annual transfusion requirements are expressed as the volume of packed, washed, or frozen-thawed red cells divided by the weight of the patient at midyear. The first

Received for publication September 26, 1988; accepted October 14, 1988.

This work was supported in part by a contract with the Commonwealth of Pennsylvania The study was presented at the annual meeting of the American Society of Hematology, Washington, DC, December 1987.

Address reprint requests to Alan Cohen, M.D., Division of Hematol- ogy. Children's Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia, PA 19104.

0 1989 Alan R. Liss, lnc.

Brief Report: Splenectomy in Thalassemia Major 255

\ I

I 2 3 4 5 a Pre- Splenectorny Years After Splenectomy

Fig. 1. Annual transfusion requirements after splenec- tomy. Transfusion requirements fell in the first year and then remained stable in (a) 8 patients evaluated 2-5 years

6 months after splenectomy were excluded from the anal- ysis. The actual volume of administered blood was used in the calculation of transfusion requirements. In eight of the 98 patient-years, the volume of one transfusion was missing. The average volume for the remaining transfu- sions in the same year was assigned to the missing data.

Two years from one patient were excluded from the study. In one of these years, the transfusion program was intensified in order to raise the pretransfusion hemoglo- bin level above 12 g/dl (120 g/L). In the other year, the patient had severe, recurrent epistaxis due to a naso- pharyngeal angiofibroma that was subsequently excised. Four patients had previously participated in a study of young red cells [6]. Blood requirements of these patients during the year of young red cell transfusions varied little

I

after splenectomy and (b) 8 patients evaluated 6-17 years after splenectomy.

from requirements with conventional red cells and are therefore included in the current study.

RESULTS

Transfusion requirements decreased by 14-66% (mean 37%) in the first year after splenectomy but re- mained stable thereafter (Fig. I ) . The change in individ- ual transfusion requirements between the first year after splenectomy and the current year was -43 to + 15 ml/kg (mean -6 ml/kg), representing no significant difference ( P >. 10 by Student's t-test for paired samples). Analysis of the eight patients who were 6 or more years from the time of splenectomy showed a similar stability of trans-

256

fusion requirements with a mean change of -7 ml/kg ( P >. 10). Overall, annual transfusion requirements were unrelated to the time since splenectomy (r = -0.28).

Blood requirements for individual patients varied little from year to year (mean annual change -0.1%). Increas- ing duration from the time of splenectomy was unrelated to the magnitude of the yearly change in transfusion re- quirements ( r= -0.19).

Fourteen of 16 patients have received regular chelation therapy before and after splenectomy . Serum ferritin lev- els for these 14 patients have fallen markedly during treatment with deferoxamine and are currently 188- 4,628 kg/L. The influence of reduced blood require- ments on iron load could not be determined precisely for each patient because of confounding factors including alteration in route or dose of deferoxamine, change in compliance and the normal change in the amount of uri- nary iron excretion as iron stores diminish.

Brief Report: Cohen et al.

DISCUSSION

The results of this study indicate that the beneficial effects of splenectomy on transfusion requirements and the rate of iron loading in thalassemia major are long- lasting. In a previous study, Engelhard et al. concluded that the improvement after splenectomy was often tem- porary, lasting only 1 or 2 years [4]. Transfusion require- ments, expressed simply as number of units per year, returned to presplenectomy levels in more than one-half of the patients. The investigators reported that the pa- tients with a short-lived response were more likely to have begun transfusion therapy and undergone splenec- tomy earlier in life than the patients with a sustained improvement. Hemoglobin levels of the patients in the study varied widely and were generally much lower than the levels of patients in the present study and the levels used in most current transfusion programs. Since weight was not included in the calculation of annual blood re- quirements in this study, the apparent reversal of the early benefits of splenectomy may have represented the expected change during normal patient growth.

In two overviews of the treatment of thalassemia ma- jor, Modell noted that most of her patients had achieved a permanent reduction in transfusion requirements after splenectomy [2 ,5] . Patients who did not have sustained improvements were on transfusion programs in which the pretransfusion hemoglobin level was less than 8.5 g/dl (85 g/L). Modell suggested that the low hemoglobin level in these patients as well as the patients in the study by Engelhard et al. facilitated the growth of accessory spleens, leading to a recurrence of hypersplenism.

Patients in the present study were treated with a con- ventional hypertransfusion program in which pre-trans- fusion hemoglobin levels were 8.5-10 g/dl (85-100 g/L). All had a sustained reduction in transfusion re- quirements after splenectomy , and the decreased rate of transfusional iron loading has presumably enhanced the removal of excessive iron stores during long-term che- lation therapy. The normally stable pattern of individual transfusion requirements after splenectomy suggests that even a moderate increase in blood consumption should prompt a search for alloantibodies or an accessory spleen.

ACKNOWLEDGMENTS

The author gratefully acknowledges the assistance of Joan Grady in the preparation of this manuscript.

REFERENCES

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2. Modell 8: Total management of thalaasaeniia major. Arch Dis Child 52:489. 1977.

3 . Cohen A. Markenson AL, Schwartz E: Transfusion requirements and splenectomy in thalassemia major. J Pediatr 97: 100. 1980.

4. Engelhard D, Cividalli G. Rachmilewitz EA: Splenectomy in homozy- gous beta thalassaemia: A retrospective study of 30 patients. Br J Hae- niatol 31:391, 1975.

5. Modell B, Berdoukas V: “The Clinical Approach to Thalassaemia.” London: Grune & Stratton. 1984, pp 130-131.

6. Cohen AR. Schmidt JM, Martin M, Barnsley W, Schwartz E: Clinical trial of young red cell transfusions. J Pediatr 104:865, 1984.