Pediatr Blood Cancer 2006;47:737739

Splenectomy and Spontaneous Remission in Children With Chronic Idiopathic Thrombocytopenic Purpura
n, MD,2,6 Mar a Cristina Rapetti, MD,1 Amadeo Rosso, Hugo Donato, MD,1,3,6,7* Armando Pico 3,5 Gabriel Schvartzman, MD, Constanza Drozdowski, MD,2 and Juan Jose Di Santo, MD4
Two hundred thirty of 696 evaluable children were identied as having chronic idiopathic thrombocytopenic purpura (ITP). Splenectomy was performed in 30 (13%), achieving remission in 22 (73%). Favorable response was associated to higher initial platelet count. Spontaneous remission was achieved by 53/200 nonsplenectomized patients (26.5%), up to 10 years from diagnosis.
MD,
4

More than half of them recovered between 6th and 12th month from diagnosis. The recovery rate was signicantly higher (P 0.03) in children aged <9 years (31.2%) than in older children (14.6%). No reliable factor predictive of response in individual cases is still available. Pediatr Blood Cancer 2006;47:737739.
2006 Wiley-Liss, Inc.

Key words:

idiopathic thrombocytopenic purpura; platelets; splenectomy; thrombocytopenia

INTRODUCTION The management of children with chronic idiopathic thrombocytopenic purpura (ITP) is controversial. Although treatment with corticosteroids, azathioprine, cyclophosphamide, vinblastine, cyclosporine, interferon, intravenous immunoglobulin (IVIG), anti-D, and rituximab have been proposed with variable grades of success [13], splenectomy still remains the most effective therapeutic option [4]. However, differing opinions regarding its timing and convenience have been stated. As some authors are reluctant to indicate splenectomy because of the risk of overwhelming post-splenectomy sepsis (OPSS), others claim that it is a safe and useful procedure. Consequently, the rate of splenectomy performed for children with chronic ITP ranges widely in different series [511]. Furthermore, a high rate of spontaneous recovery up to 10 years from the diagnosis has been reported in several studies [9,10,1215]. Therefore, the controversy between active management (splenectomy) and passive management (observation) for these patients is currently set out. Because of the marked differences in results of published trials and contradictory opinions expressed by many authors, we present results regarding the spontaneous or splenectomy-induced remission in a multicentered series of children in Argentina, attempting to clarify some issues on the outcome of chronic ITP. PATIENTS AND METHODS Information concerning children (aged 2 months to 15 years) with ITP diagnosed from 1981 to 2005 is being recorded in a database since 1997. Data regarding 844 children treated in seven hospitals have been recorded to date. The following data are obtained for each patient: age, gender, seasonal incidence, antecedent of preceding infection, initial platelet count, type of bleeding manifestations (dry or wet purpura), severity of bleeding at diagnosis, received therapies, and nal outcome. Chronic ITP is dened as persistence of platelet count <150 109/L at 6 months from diagnosis. Long-lasting
2006 Wiley-Liss, Inc. DOI 10.1002/pbc.20982

antibiotic prophylaxis with penicillin or amoxicillin was administered to every splenectomized patient. Since 1995, all patients were immunized against Streptococcus pneumoniae, Haemophilus inuenzae, and Neisseria meningitidis. RESULTS The outcome was evaluated on 696 children with adequate follow-up. Of them, 230 (32.6%) were considered as having chronic ITP. Splenectomy was performed in 30 patients (13%), at a mean time of 2.5 1.4 years (range 16 years) from the diagnosis. Mean follow-up of these children was 58.4 46.3 months (range 12156 months). Normalization of platelet count was achieved in 22 (73.3%). Age at diagnosis (less or more than 9 years old), gender, severity of bleeding, length of time from diagnosis to splenectomy, and previous treatment with IVIG were not signicantly different between patients who did or did not achieve complete remission. Initial platelet count was signicantly higher in patients with favorable response to splenectomy than in nonresponders (14.9 13.9 109/L vs. 10.0 24.3 109/L, respectively; P 0.02). No child died because of OPSS. Fifty-three of 200 non-splenectomized patients (26.5%) with chronic ITP achieved spontaneous remission between 6 months and 10 years from diagnosis; 30 of them (56.6%) recovered between the 6th and the 12th month from the diagnosis. Gender, initial platelet count, and severity at diagnosis were not signicantly different between children, whether or not they achieved spontaneous remission. The recovery rate was signicantly higher in children aged less
o de San Justo, Buenos Aires, Argentina; 2Hospital Hospital del Nin nica y Maternidad Alejandro Posadas, Buenos Aires, Argentina; 3Cl os Vilela, Suizo-Argentina, Buenos Aires, Argentina; 4Hospital de Nin nico Bancario, Buenos Aires, Rosario, Santa Fe, Argentina; 5Policl Argentina; 6Hospital Naval Pedro Mallo, Buenos Aires, Argentina; 7 Hospital San Juan de Dios, Buenos Aires, Argentina *Correspondence to: Hugo Donato, Ocampo 3308, San Justo, 1754 Buenos Aires, Argentina. E-mail: hugodonato@aol.com Received 20 June 2006; Accepted 20 June 2006

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Donato et al.
TABLE I. Characteristics of Splenectomized and NonSplenectomized Children With Chronic ITP Achieving Complete Remission Splenectomized Non-splenectomized patients patients n Age (years) Gender Female (n) Male (n) Initial platelet count (109/L) Bleeding manifestations Dry purpuraa (n) Wet purpurab (n)
a b

than 9 years (31.2%) than in children aged 9 or more (14.6%) at the diagnosis (P 0.03) (Fig. 1). Comparison between patients who achieved either spontaneous remission or splenectomy-induced remission (Table I) showed that children with spontaneous remission were signicantly younger than splenectomized patients (5.0 3.4 years vs. 8.0 4.4 years, respectively; P 0.008). Gender, initial platelet count, and severity at diagnosis showed no signicant difference between both groups. DISCUSSION The rate of splenectomy performed for chronic ITP in different pediatric series ranges between 9% and 39% [511]. In our population, only 30 of 230 children (13%) with chronic ITP underwent splenectomy, a rate very close to the lowest published percentage. The 73.3% of our splenectomized patients achieved normal platelet count, in agreement with the 72.5% rate of remission reported by Blanchette and Price [4] in a review of published studies. Although patients with higher platelet count at diagnosis showed a more favorable response to splenectomy in our population, these data must be analyzed with caution because of the small number of non-responding patients. No correlation was found between age and post-splenectomy outcome; data in the literature concerning this issue show controversial results [6]. No association between postsplenectomy outcome and other variables (gender, severity, time from diagnosis, previous treatment with IVIG) was found. The analysis of the remaining 200, non-splenectomized children with chronic ITP showed that more than 26% of them achieved normalization of platelet count at different lengths of time from the diagnosis, up to 10 years. Results of published studies show a great disparity concerning the occurrence of spontaneous remission in children

P 0.008 0.858 0.858 0.409

22 8.0 4.4 10 12 14.9 13.9

53 5.0 3.4 27 26 12.7 13.3

14 8

39 14

0.560 0.560

Petechiae and ecchymoses; oral mucosal bleeding. Epistaxis, gastrointestinal bleeding, menorrhagia, intracranial hemorrhage.

Fig. 1. Remission rate according to age at diagnosis. The recovery rate was signicantly higher in children aged less than 9 years than in children aged 9 or more throughout the follow-up period (P 0.03).
Pediatr Blood Cancer DOI 10.1002/pbc

with chronic ITP, with rates ranging from 6% to 79% [1,4,7,10,1218]. However, in our group more than half of patients who spontaneously normalized the platelet count achieved early remission, between the 6th and the 12th month after the diagnosis. The issue regarding the length of time from diagnosis to spontaneous remission has not been exhaustively investigated in most trials. Jayabose et al. [9] reported spontaneous remission in 35 of 62 patients (56%); in agreement with our observation, 13 of them (37%) had achieved remission at 12 months from the diagnosis. Six months is the arbitrarily established limit unanimously accepted to dene an ITP as chronic, but this subject is currently under reassessment. If we should consider that the limit to dene chronic ITP was 12 months instead of 6 months, the rate of spontaneous remission in our population should be as low as 13.5%. In our patients, the only variable having a signicant inuence on the chance of spontaneous remission was age, with children aged 9 years or more showing a signicantly lower rate of recovery (14.6%) than younger children (31.2%). Our rate of spontaneous remission in older children is very close to the 10.3% reported by Lowe and Buchanan [18] in their study performed on patients diagnosed during the second decade of life. Other reports could not nd such an association [9]. Several factors are usually evaluated prior to indicate a splenectomy: the risk of OPSS, the perioperative morbidity, the chance of splenectomy failure, the very low mortality rate of chronic ITP, the probability of spontaneous remission, and the impact of persistent thrombocytopenia on quality of life. Authors who prefer a passive management of children with chronic ITP argue that the reported high rate of spontaneous remission makes the splenectomy unnecessary in the majority of cases, given that the patient will probably achieve remission in a few years [10,19,20]. Others suggest that splenectomy should be considered almost exclusively in

Splenectomy and Spontaneous Remission in Chronic ITP

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children with platelet count <20 109/L at 6 months from the diagnosis who require continuous therapy for their severe thrombocytopenia [4]. On the contrary, other authors claim that the remission induced by splenectomy results in a signicant improvement in quality of life of affected children, a benet that exceeds the minimal risk of death due to OPSS [6,8,18]. Splenectomy is rarely performed before 12 months from the diagnosis, and only in patients with life-threatening bleeding. Nearly all authors agree with this policy [4,6,19,20]. According to our data, the probability to achieve spontaneous remission after 12 months from the diagnosis is low. Therefore, these results could give additional support to the indication for elective splenectomy, but they must be conrmed by prospective studies. There is general agreement that the risk of OPSS is inversely related to the age [4,6]. Children aged less than 45 years are more prone to develop sepsis due to encapsulated germs than older children. Consequently, splenectomy in younger children must be delayed as more as possible to diminish this risk [6]. Furthermore, the rate of spontaneous remission in our study was signicantly higher in patients less than 9 years than in older patients, a nding that should reinforce the convenience to defer the procedure in this age group. However, other trials have not demonstrated any relationship between age and spontaneous recovery [9]. In conclusion, an individualized patient evaluation is necessary to indicate a splenectomy: risk of OPSS, probability of spontaneous remission, and age must be carefully weighted before performing the procedure. However, no reliable factor predictive of response to splenectomy in individual cases is currently available. Ongoing prospective intercontinental studies on long-lasting follow-up of children with ITP and results of splenectomy will probably give a most accurate response to many of these issues. REFERENCES
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Pediatr Blood Cancer DOI 10.1002/pbc