Abstract
Amaç: Trombositopeni çocuklarda sık görülen bir hematolojik bulgudur. Bu çalışmada trombositopenili çocukların demografik, laboratuvar, genetik özelliklerinin ve prognozlarının değerlendirilmesi amaçlandı. Gereç ve Yöntem: Bu retrospektif çalışmaya Aralık 2021-Ağustos 2023 tarihleri arasında Düzce Üniversitesi Tıp Fakültesi Çocuk Hematoloji-Onkoloji Polikliniği’nde trombositopeni tanısı konulan çocuklar (n=82) dahil edildi. İdiyopatik trombositopenik purpurası (n=41) olan ve olmayan (n=41) trombositopenili olguların laboratuvar, klinik, ve tedavileri karşılaştırıldı. Seçilmiş olgularda klinik ekzom yeni nesil sekanslama ile gen analizi yapıldı. Bulgular: İmmun trombositopenik purpura (İTP)’li olmayan çocuklarda (n=41) İTP’lilere göre (n=41) ateş (p<0,001), enfeksiyon (p<0,001), bisitopeni veya pansitopeni (p=0,013) ve solukluk (p=0,014) oranları daha yüksekti. İTP’li hastalarda, İTP’li olmayan hastalara göre trombosit sayısının ortanca değeri (p<0,001) anlamlı olarak daha düşük ve ortalama nötrofil düzeyleri (±SD) (p=0,003) daha yüksekti. Enfeksiyonu olan çocuklarda (n=22), enfeksiyonu olmayanlara (n=60) göre yüksek ateş (p<0,001), solukluk (p<0,001), bisitopeni ve pansitopeni (p=0,04) daha sık ve ortalama trombosit düzeyleri (± SD) ile nötrofil düzeyleri (p=0,004) daha düşük bulundu. Ortanca trombositopeni süresi (15 güne karşın 90 gün) (p=0,04) enfekte grupta daha kısaydı. Hafif makrotrombositopenisi olan bir erkek çocukta klinik ekzom yeni nesil sekanslama analizinde üç yeni variant tanımlandı. ANKRD26 geninde 3:c. 340A >G (p. Arg114Gly) varyantı, SAMD9 geninde 002G>A (p. Asp668Asn) varyantı ve TUBB1 geninde 1342 G>T (p. Asp448Tyr) varyantı saptandı. Yeni TUBB1 varyantı hastanın kliniği ile uyumlu bulundu. Sonuç: Enfeksiyona bağlı trombositopeni, İTP’ye göre daha yüksek trombosit sayıları ile daha hızlı iyileşir. Konjenital makrotrombositopeni tanısı için atipik İTP’li olgularda klinik ekzom yeni nesil sekanslama analizi önerilir.
References
- Bhatia I, Sharma A, Guleria S, et al. Thrombocytopenia in Children: A large prospective study on clinical manifestations, seasonal variation, etiology, and outcome. J Assoc Physicians India. 2023;71(3):11-12.
- Despotovic JM, Grimes AB. Pediatric ITP: is it different from adult ITP? Hematology Am Soc Hematol Educ Program. 2018;2018(1):405-411.
- Schifferli A, Heiri A, Imbach P, et al. Misdiagnosed thrombocytopenia in children and adolescents: analysis of the Pediatric and Adult Registry on chronic ITP. Blood Adv. 2021;5(6):1617-1626.
- Berrueco R, Sebastián E, Solsona M, et al. Secondary immune thrombocytopenia in children: Characteristics and outcome of a large cohort from two Spanish centres. Acta Paediatr. 2021;110(6):1952-1958.
- Li RW, Fu RF, Chen YF, et al. Clinical Analysis of Hospitalized Children with Primary Immune Thrombocytopenia. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021;29(2):574-580.
- Lee YK, Yoon HS, Lee EH, et al. Can we predict the clinical course of immune thrombocytopenia in children by the mean platelet volume? A preliminary study. Clin Lab. 2021;67(3).
- Tyagi R, Basu S, Kumar A, et al. Thrombocytopenia in a child with polyarthritis: A pointer to gray platelet syndrome. Pediatr Blood Cancer. 2023;70(2):e29916.
- Tyrrell L, Scruggs M, Kerwin A, et al. The role of peripheral blood smear examination in the evaluation of suspected platelet-related disorders in children: A practical approach and an illustrated review. Malays J Pathol. 2022;44(3):397-413.
- Çalışkaner ZO, Abdul Waheed A, Tuzlakoğlu Öztürk M, et al. Identification of novel TUBB1 variants in patients with macrothrombocytopenia. Turk J Med Sci. 2021 ;51(2):490-500.
- Palma-Barqueros V, Bury L, Kunishima S,et al. Expanding the genetic spectrum of TUBB1- related thrombocytopenia. Blood Adv. 2021;5(24):5453-5467. Erratum in: Blood Adv. 2023;7(6):877.
- Matsumura T, Nakamura-Ishizu A, Takaoka K, et al. TUBB1 dysfunction in inherited thrombocytopenia causes genome instability. Br J Haematol. 2019;185(5):888-902.
- Hou Y, Shao L, Zhou H, et al. Identification of a pathogenic TUBB1 variant in a Chinese family with congenital macrothrombocytopenia through whole genome sequencing. Platelets. 2021;32(8):1108-1112.
- Perez Botero J, Dugan SN, Anderson MW. ANKRD26-Related Thrombocytopenia. 2018 Jun 21. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm. nih.gov/books/NBK507664/
- Raskind WH, Chen DH, Bird T. SAMD9L Ataxia-Pancytopenia Syndrome. 2017 Jun 1 [Updated 2021 Feb 4]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi. nlm.nih.gov/books/NBK435692/
Abstract
Aim: Thrombocytopenia is a common hematologic finding in children. This study evaluated the demographic, laboratory and genetic characteristics and prognosis of children with thrombocytopenia. Material and Method: This retrospective study included children (n=82) examined with thrombocytopenia at Düzce University Faculty of Medicine Pediatric Hematology-Oncology Clinic between December 2021 and August 2023. Laboratory, clinical, and treatment characteristics of patients with idiopathic thrombocytopenic purpura (n=41) and without thrombocytopenia (n=41) were compared. Gene analysis was performed by clinical exome next-generation sequencing in selected cases. Results: Children without idiopathic thrombocytopenic purpura (ITP) (n=41) had higher rates of fever (p<0.001), infection (p<0.001), cytopenia or pancytopenia (p=0.013) and pallor (p=0.014) than children with ITP (n=41). The median platelet count was significantly lower (p<0.001) and neutrophil levels (mean ± SD) (p=0.003) were higher in patients with ITP compared to patients without ITP. In children with infection (n=22), high fever (p<0.001), pallor (p<0.001), cytopenia and pancytopenia (p=0.04) were more frequent and mean platelet levels (± SD) and neutrophil levels (p=0. 004) were lower than those without infection (n=60). The median duration of thrombocytopenia (15 days vs. 90 days) (p=0. 04) was shorter in the infected group. Three novel variants were identified by clinical exome next-generation sequencing analysis in a boy with mild macrothrombocytopaenia. Three novel variants in one patient in the genes; a three :c. 340A >G (p. Arg114Gly) variant, a 002G>A (p. Asp668Asn) variant in the ANKRD26 gene in the SAMD9 gene and in the TUBB1 gene a 1342 G>T (p. Asp448Tyr) variant. The new TUBB1 variant was consistent with the patient’s clinical presentation. Conclusion: Infection-associated thrombocytopenia improves faster with higher platelet counts than ITP. Clinical exome next-generation sequencing analysis is recommended in cases with atypical ITP to diagnose congenital macrothrombocytopaenia.
References
- Bhatia I, Sharma A, Guleria S, et al. Thrombocytopenia in Children: A large prospective study on clinical manifestations, seasonal variation, etiology, and outcome. J Assoc Physicians India. 2023;71(3):11-12.
- Despotovic JM, Grimes AB. Pediatric ITP: is it different from adult ITP? Hematology Am Soc Hematol Educ Program. 2018;2018(1):405-411.
- Schifferli A, Heiri A, Imbach P, et al. Misdiagnosed thrombocytopenia in children and adolescents: analysis of the Pediatric and Adult Registry on chronic ITP. Blood Adv. 2021;5(6):1617-1626.
- Berrueco R, Sebastián E, Solsona M, et al. Secondary immune thrombocytopenia in children: Characteristics and outcome of a large cohort from two Spanish centres. Acta Paediatr. 2021;110(6):1952-1958.
- Li RW, Fu RF, Chen YF, et al. Clinical Analysis of Hospitalized Children with Primary Immune Thrombocytopenia. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021;29(2):574-580.
- Lee YK, Yoon HS, Lee EH, et al. Can we predict the clinical course of immune thrombocytopenia in children by the mean platelet volume? A preliminary study. Clin Lab. 2021;67(3).
- Tyagi R, Basu S, Kumar A, et al. Thrombocytopenia in a child with polyarthritis: A pointer to gray platelet syndrome. Pediatr Blood Cancer. 2023;70(2):e29916.
- Tyrrell L, Scruggs M, Kerwin A, et al. The role of peripheral blood smear examination in the evaluation of suspected platelet-related disorders in children: A practical approach and an illustrated review. Malays J Pathol. 2022;44(3):397-413.
- Çalışkaner ZO, Abdul Waheed A, Tuzlakoğlu Öztürk M, et al. Identification of novel TUBB1 variants in patients with macrothrombocytopenia. Turk J Med Sci. 2021 ;51(2):490-500.
- Palma-Barqueros V, Bury L, Kunishima S,et al. Expanding the genetic spectrum of TUBB1- related thrombocytopenia. Blood Adv. 2021;5(24):5453-5467. Erratum in: Blood Adv. 2023;7(6):877.
- Matsumura T, Nakamura-Ishizu A, Takaoka K, et al. TUBB1 dysfunction in inherited thrombocytopenia causes genome instability. Br J Haematol. 2019;185(5):888-902.
- Hou Y, Shao L, Zhou H, et al. Identification of a pathogenic TUBB1 variant in a Chinese family with congenital macrothrombocytopenia through whole genome sequencing. Platelets. 2021;32(8):1108-1112.
- Perez Botero J, Dugan SN, Anderson MW. ANKRD26-Related Thrombocytopenia. 2018 Jun 21. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm. nih.gov/books/NBK507664/
- Raskind WH, Chen DH, Bird T. SAMD9L Ataxia-Pancytopenia Syndrome. 2017 Jun 1 [Updated 2021 Feb 4]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi. nlm.nih.gov/books/NBK435692/
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences (Other) |
| Journal Section | Research Article |
| Authors | |
| Publication Date | October 31, 2023 |
| Submission Date | September 11, 2023 |
| Published in Issue | Year 2023 Volume: 1 Issue: 3 |
