Sultan Aydin Koker

Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively. None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

Thrombotic Microangiopathy with Complement Factor H Gene Mutations Unassociated with Atypical Hemolytic Uremic Syndrome.

To the Editor, Atypical hemolytic uremic syndrome (aHUS) is a rare multigenic disorder characterized by thrombotic microangiopathy (TMA). Among the genes that are associated with aHUS, mutations in the complement factor H (CFH) gene are the most common genetic cause of the disease. Several specific gene mutations have been identified in patients with aHUS [1,2,3]. A 5-year-old boy was admitted to our hospital with fatigue. Physical examination revealed pallor and hepatomegaly. His blood pressure was within the normal range. A blood smear showed hemolysis with 10% schistocytes and polychromasia. He had anemia with 5.5 g/ dL hemoglobin level and 14.6% reticulocyte level. He had also thrombocytopenia (48,000/mm3) and elevated lactate dehydrogenase (LDH) as 1066 U/L. A direct Coombs test was negative. The other blood parameters of the patient were as follows: haptoglobin 5 mg/dL (reference range: 41-165 mg/dL), C3 122 mg/dL (reference range: 79-152 mg/dL), creatinine level 0.5 mg/dL, blood urea nitrogen 12 mg/dL, and indirect bilirubin 7 mg/dL. Urine analysis was normal. On the second day of admission, the patient’s thrombocyte count dropped to 38,000/mm3, his LDH level remained elevated, and schistocytes were still present on his peripheral blood smear. As for the blood smear and other TMA symptoms, first plasmapheresis was started, which lasted 20 weeks. Then treatment was continued with 600 mg of eculizumab weekly for the first three weeks and followed by once every 2 weeks (total 11 doses). Although the patient had TMA symptoms he didn’t have renal insufficiency. Also ADAMTS-13 activity was 48% (reference range: 40%-130%) and ADAMTS-13 antibody was negative. Four months after stopping eculizumab, the patient’s levels of hemoglobin, thrombocytes, reticulocytes, haptoglobin and LDH were 11 g/dL, 150,000/mm3, 0.87%, 46.4 mg/dL (reference range: 41-165 mg/dL) and 385 U/L, respectively. Informed consent was obtained for genetic testing and publishing the patient’s data from his parents. DNA sequencing analysis of the patient revealed a homozygous p.His402Tyr mutation due to a p.1204 C>T change in exon 9, a homozygous p.Ala307Ala mutation due to a p921A>C change in exon 7 and a heterozygous p.Ala473Ala mutation due to a p.1419G>A change in exon 10 of the CFH gene (Figure 1).

Central line bundle for prevention of central line–associated bloodstream infection for totally implantable venous access devices (ports) in pediatric cancer patients:

Objective: The clinical impact of central line bundle programs for central line–associated bloodstream infections has been well demonstrated in intensive care units. However, the experience of central line bundle programs in totally implantable venous access devices (ports) in pediatric-hematology patients was limited. Methods: A retrospective study was designed to compare and evaluate the clinical impact of implementing a central line bundle for a 2-year 5-month period, including 10 months of prebundle period, 11 months of central line bundle (that includes needleless split-septum devices), and finally 8 months of central line bundle period in which single-use prefilled flushing devices were added to the previous central line bundle. Results: During the prebundle period, the rate of 14.5 central line–associated bloodstream infections per 1000 CL-days had decreased to 5.49 CLABSIs per 1000 CL-days in the first bundle period. The incidence rate ratio with these two groups was 0.379, indicating a relative risk reduction of 62% (p = 0.005). By the addition of single-use prefilled flushing devices to the first bundle program, the central line–associated bloodstream infection rate decreased to 2.63 per 1000 CL-days. Port removal rate due to central line–associated bloodstream infections was 0.46 per 1000 catheter days in the bundle period, which was significantly lower than in the prebundle period in which port removal rate was 4.5 per 1000 catheter days (p < 0.001). Conclusion: Central line bundle programs were found to be effective in decreasing central line–associated bloodstream infection rates, improving patients’ quality of life by preventing ports removal due in pediatric cancer patients.

The Evaluation of Taking Iron Supplements in Children Aged 6 Months-2 Years

156 ©Telif Hakkı 2017 Ege Üniversitesi Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları Anabilim Dalı ve Ege Çocuk Vakfı The Journal of Pediatric Research, Galenos Yayınevi tarafından basılmıştır. Ya z›fl ma Ad re si/Ad dress for Cor res pon den ce Dr. Tuba Hilkay Karapınar, Dr. Behçet Uz Çocuk Hastalıkları ve Cerrahisi Eğitim ve Araştırma Hastanesi, Çocuk Hematoloji-Onkoloji Kliniği, İzmir, Türkiye Tel.: +90 232 411 63 11 E-posta: thkarapinar@yahoo.com ORCID ID: orcid.org/0000-0002-4714-332X Ge liş ta ri hi/Re cei ved: 10.10.2016 Ka bul ta ri hi/Ac cep ted: 24.03.2017 The Evaluation of Taking Iron Supplements in Children Aged 6 Months-2 Years

Idiopathic pulmonary hemosiderosis mimicking iron deficiency anemia: a delayed diagnosis?

Idiopathic pulmonary hemosiderosis (IPH) is an uncommon chronic disorder in children. It is characterized by recurrent pulmonary hemorrhage and may result in hemoptysis and pulmonary insufficiency. The most common hematologic manifestation of IPH is iron deficiency anemia. The etiology of IPH is not known and its diagnosis may be difficult due to the variable clinical courses. The most helpful signs for identifying IPH are iron deficiency anemia and recurrent or chronic cough, hemoptysis, dyspnea, wheezing. We report here 5 pediatric cases of IPH presenting with iron deficiency anemia and without pulmonary symptoms. Mean corpuscular volume was low in all patients; iron was low in 4 out of 5 cases; total iron binding capacity was high in all of them; ferritin was low in 3 patients. At follow up, none of them had responded successfully to the iron therapy. Although they didn’t present with pulmonary symptoms, chest radiographs incidentally revealed diffuse reticulonoduler shadows in all of them. Computed tomography revealed diffuse ground-glass opacities, consolidation, increased density. The diagnosis was confirmed by the detection of hemosiderin-laden macrophages in bronchoalveolar lavage fluid and gastric aspirate. If patients with iron deficiency anemia don’t respond to iron therapy, they should be examined for IPH. Chest radiographs should be taken even in absence of pulmonary symptoms. Early diagnosis is important for a timely management of IPH.

Chronic Neutropenia in Childhood: Experience From a Single Center.

Chronic neutropenia (CN) is defined as neutropenia that persists for >3 months; it is caused by a heterogeneous group of diseases in children. The aim of the present study was to evaluate the significance and clinical manifestations of CN in children at a single children’s hospital. Between October 2004 and April 2014, CN patient data were evaluated retrospectively. Thirty-one patients were assessed in this study. Thirteen of them (41.9%) were younger than 12 months of age at initial diagnosis. There was no difference in the absolute number of neutrophils at diagnosis between the children aged younger than 12 months and those aged 12 months and older at CN onset. Twenty-two of the patients (70.9%) were diagnosed during treatment for acute infections. A total of 11 patients (35.5%) were hospitalized because of recurrent infections. Most of the recurrent infections occurred in the lungs (81.8%). Congenital neutropenia (CoN) was identified in 14 patients (45.1%). Eight of 14 patients (57.1%) required granulocyte-colony stimulating factor treatment, and none of them experienced adverse effects from this treatment. Fifteen patients (48.3%) were diagnosed with idiopathic neutropenia. Comparison between the idiopathic and CoN groups revealed no differences in age, the absolute number of neutrophils, or the presence of infection at diagnosis; however, differences were detected in sex and the rate of spontaneous recovery from neutropenia. Ten of the patients (32.2%) experienced spontaneous recovery from neutropenia during a follow-up period of 7 to 52 months. In current study, we found a higher CoN ratio in the CN patients compared with previous reports, which may be due to the high rate of consanguineous marriages in our country. However, the finding of CN requires several laboratory investigations, prolonged follow-up, and advanced molecular analysis, and its etiology can remain idiopathic.

Torticollis in a haemophilic infant with inhibitor: a case of spinal epidural haematoma.

Central nervous system bleeding, which can be a life-threatening complication, is seen in 2.7% of patients with haemophilia. Spinal epidural haematomas represent about one-tenth of such cases. Here, we report on a 10-month-old boy with severe haemophilia A, who presented with torticollis. Although administration of factor VIII at a dose of 50 U/kg, the patient developed flaccid paralysis of the upper extremities. Factor VIII inhibitor screen was positive. Magnetic resonance imaging of the spine revealed spinal epidural haematomas, extending from C-1 to the cauda equina. Treatment was continued with recombinant activated factor VIIa without surgery. After 1 month, complete neurological recovery was achieved and fully resolved haematomas were detected on spinal MRI. A prompt radiological evaluation of the cervical spine with MRI should be made in patients with haemophilia presenting with torticollis. In addition, in the case of life-threatening bleeding in patients with haemophilia, the possibility of an inhibitor should be kept in mind.