Çocukluk çağında ITP ve farklı klinik seyir: Tek merkezli 16 yıllık deneyim

Variant clinal courses in children with ITP: 16 year experience of a single-medical center

Özet

Amaç: Idiopatik trombositopenik purpura (ITP), çocukluk çağında sık görülen edinsel bir trombositopeni nedenidir. Hastalığın, klinik seyri ile ilgili tek merkezli, uzun süreli izleme ait kaynaklar yetersizdir. Ayrıca, literatürde, bilinen akut ve kronik seyir yanında farklı klinik seyirlerin de olduğundan söz edilmektedir. Bu çalışmada amacımız, hastanemiz Çocuk Hematoloji Bölümü'nde ITP tanısı alarak izlenen olguların başvuru bulguları, klinik seyirlerindeki farklılıklar, tedavi protokollerine kısa ve uzun dönem yanıtlarını değerlendirmektir. Yöntem: Hastanemiz Çocuk Sağlığı ve Hastalıkları Klinikleri Hematoloji Ünitesi'nde Ocak 1990-Haziran 2006 tarihleri arasında ITP tanısı alarak izlenen 491 olgudan 6 ay-16 yaş arasındaki 350 olgu çalışma grubunda incelendi. Trombositopenisi 6 aydan kısa süren olgular akut ITP, 6 aydan daha uzun süren olgular kronik ITP kabul edildi. Tedavi almaksızın en az 3 ay süre ile trombosit sayısı normal sınırlarda seyreden ve ardından trombositopenisi tekrarlayan olgular rekürren ITP olarak kabul edildi. Kronik ITP'H olgular remisyona girmeyen ve geç remisyona giren olmak üzere ayrıca iki alt grupta incelendi. Tanıda ciddi trombositopenisi ( 150xl09A- tam remisyon, trombosit sayısı 50-149 xlO9/L kısmi remisyon, 20 xlO9/L, başvuru yaşının >10 yaş olmanın kronik ITP olasılığını 2 kat arttırdığı görüldü. Kronik ITP'H olguların %77.5'ini oluşturan remisyona girmeyen grupta tanı yaşı median 7.9 yıl, %22.5'ini oluşturan geç remisyona giren grupta median 3.5 yıl bulundu ve aralarında anlamlı fark saptandı (p 20xl09/L olmasının risk faktörleri olarak değerlendirilebileceği anlaşılmıştır.

Abstract

Aim: Idiopathic thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia in children. However, single-institution, long-term, natural history data are limited. Besides, clinical course and treatment outcome reported in the literature are quite variable. The objective of this study is to evaluate the presenting features, variations in the clinical courses, response to therapy and long-term outcome in patients with ITP treated at our Pediatric Hematolgy Division. Methods: 350 out of 491 patients with ITP between the ages of 6 months to 16 years diagnosed and followed-up for the last 16 years (Jan. 1990 to June 2006) at Izmir Tepecik Teaching Hospital, Pediatric Hematology Division were included in the this retrospective study. Patients having low platelet counts (<15OxlO9/L) < 6 months were accepted as acute ITP; thrombocytopenia persisting for more than 6 months after initial diagnosis were accepted as chronic ITP. Patients showing recurrences after at least 3 months of remission sustained without treatment were accepted as recurrent ITP. Chronic ITP patients were also evaluated in 'non-remission' and 'late-remission' subgroups. Patients with platelet counts < 20xl09/L and/or bleeding symptoms at diagnosis were treated. Treatment consisted of high dose methylprednisolon (HDMP), intravenous immunoglobulin (IVIG) and/or combination therapy of HDMP and IVIG. Complete and partial response were defined as platelet count >150 xlO9/L and 50-149 xlO9/L (including clinical recovery), repectively. Platelet count <50 xlO9/L was defined as non-responsive. Patients with acute vs chronic ITP, acute vs recurrent ITP and chronic vs recurrent ITP were compared in terms of age, age at diagnosis, gender, initial platelet count, initial response, long-term response to therapy and total duration of follow-up. In patients with recurrent ITP, number of recurrences, interval between the recurrences and the duration past after the last recurrence was also noted. In splenectomized patients response rate, clinical course and duration of follow-up after splenectomy was established. For statistical analysis SPSS for Windows, version 13.0 was used. Independent Samples T Test, Pearson Ki-Square, Mann-Whitney U test and Linear Regression were used in statistical evaluation. P< 0.05 was accepted as statistically significant. Results: Among 350 patients with ITP 186 were female; 93.7% had presented with minor bleeding symptoms (skin and/or mucousale hemorrhage). Median age at diagnosis and median initial platelet count were 5 years (6 months to 16 years) and 9.5 xlO9/L , respectively. Overall patients were followed-up for median 3.5 years with a range of 6 months to 14.5 years. The clinical course of the patients were found as acute, chronic and recurrent in 63.8%, 29.1% and 7.1%, respectively. Acute cases presented at a younger age than both chronic and recurrent cases 4.5, 6.2 and 6.5 years, respectively (p<0.05) (p<0.05). Initial platelet counts in acute and recurrent ITP patients were significantly lower than in chronic ITP patients (p<0.05). Platelet count >20xl09/L and initial diagnosis age >10 years were found to increase the probability of chronic outcome by at least 2-jolds. Concerning the 102 chronic ITP patients, 77.5% was found to be in the non-remission and 22.5% in the late-remission group within the follow-up period. Median age at diagnosis of the patients in non-remission and late-remission group was 7.9 years and 3.5 years, respectively (p<0.05). Late-remission chronic ITP patients achived remission in median 1.5 years (0.6-5.3 years). Concerning the recurrent ITP patients, median age at initial diagnosis was 6.2 years (1.8-12.5 years). Within the follow-up period of 1.4 to 11.7 years these patients had undergone 1-4 recurrences. 29.4% (n=30) of the 102 chronic ITP patients were splenectomized and 24 (80%) patients responded to splenectomy. One male patient with non-remission chronic ITP developed intracranial hemorrhage at the sixth-month of diagnosis (platelet count 7xlO9/L). None of the patients died. Conclusion: ITP in childhood is a common disease with low morbidity and mortality. Natural course of the disease is variable. Besides acute and chronic, form, recurrent form which is about 7% of all ITP patients, should be considered. The clinical course, response to treatment and ultimate outcome is more like acute form than chronic form in these patients: Chronic ITP patients with late remission should also be considered. In prediction of chronic course of the disease initial diagnosis age of older than 10 years, unresponsiveness to initial therapy and initial platelet count over 20xl09/L can be evaluated as risk factors.