Evaluation of coagulation parameters and impact of transfusion on coagulation in patients with beta thalassemia major.

There have been several studies that have shown that patients with beta thalassemia major are at a higher risk of thrombosis due to the procoagulant activity of thalassemic erythrocytes, decreased liver synthetic function, increased platelet activity and vascular endothelial activation attributed to chronic oxidative stress, although there are no established tests to predict thrombotic risk in TM patients. In this study, we evaluated whether or not the platelet function analyser (PFA-200) and thrombin generation test (TGT) would be useful tools to identify hypercoagulability and risk of thrombosis in thalassemia major patients. The study included 50 patients with thalassemia major and 104 healthy control group. Pretransfusion and posttransfusion PFA-200 and TGT results were compared with control group. We found that median C/ADP and C/EPI values in the thalassemia major group were greater in both the pre and posttransfusion samples than the C/ADP and C/EPI results from the control group. The TGT results showed there was no difference between control group and the results from the thalassemia major group. The TGT and PFA-200 testing did not identify hypercoagulability nor identify clear testing parameters to predict a thalassemia major patient's risk of thrombosis. There may be other mechanisms/causes yet unidentified that could better explain thalassemia major patient's increased risk from thromboembolic events.

Idiopathic Hypereosinophilic Syndrome Associated With Pulmonary Hypertension in an Infant.

Hypereosinophilic syndrome (HES) is a very rare disease during childhood. It involves the different organs like skin, gastrointestinal system, heart and lungs, besides pulmonary hypertension (PHT) is a very rare morbidity of HES that may cause life-threatening complications. PHT improves with the treatment of hypereosinophilia, without the need for pulmonary vasodilator therapy. Here, we present a case of PHT developed after recovery of pulmonary infiltration in an infant with idiopathic HES. We revealed that pulmonary pressure returned to normal range in parallel with the decrease in eosinophil count with steroid treatment.

Posterior Reversible Encephalopathy Syndrome in Childhood Hematological/Oncological Diseases: Multicenter Results.

The aim of the study was to analyze the characteristics of posterior reversible encephalopathy syndrome (PRES) cases treated at 10 different institutions in our country. Fifty-eight patients diagnosed with PRES were included in this study. The data of PRES cases from 10 departments of pediatric hematology/oncology were analyzed. The mean age of the patients at the time of diagnosis of PRES was 8.95±3.66 years. Most patients (80.4%) had a primary diagnosis of acute leukemia. Patients received chemotherapy (71.4%) and/or used steroids within 14 days before the diagnosis of PRES (85.7%). Hypertension was found in 83.9% of the patients. Twenty-six patients had infections and 22 of them had febrile neutropenia. The most common electrolyte disorders were hypocalcemia, hypomagnesemia, and hypopotassemia. Six patients had tumor lysis syndrome and 4 had inappropriate antidiuretic hormone syndrome. Magnetic resonance imaging was used for diagnosis in all patients. The most commonly involved regions by magnetic resonance imaging were occipital (58%), parietal (51%), and frontal lobes (45%), respectively. Twenty-five patients required intensive care and 7 patients were intubated. In conclusion, PRES may develop during the follow-up and treatment of hematological diseases. In addition to steroid and intense combined chemotherapies, immunosuppressive agents and hypertension are also factors that may be responsible for PRES.

Central nervous system lesions in Fanconi anemia: Experience from a research center for Fanconi anemia patients.

BACKGROUND: Brain atrophy, abnormal pituitary morphology, corpus callosum, and posterior fossa abnormalities have been described in patients with Fanconi anemia (FA). We aimed to provide an overview of cranial neuroimaging findings and to evaluate the clinical implications in FA patients. PROCEDURE: Cranial magnetic resonance imaging (MRI) studies of 34 patients with FA were retrospectively evaluated, and patients' clinical data were correlated with the imaging findings. RESULTS: The patients' median age was 17.6 (range, 3.9-28) years. At least one pathological brain imaging finding was demonstrated in 22 (65%) patients. These findings included corpus callosum abnormalities and other related supratentorial malformations in nine, pituitary abnormalities in eight, craniovertebral junction and posterior fossa abnormalities in eight, vascular lesions in six, and intracerebral calcifications in two patients. Among the 22 patients who had abnormal cranial MRI findings, six (27%) had mild to moderate intellectual disability (ID), three (14%) had epilepsy, one (5%) had mild hearing loss, and one patient (5%) had hemiplegia. Among these 34 patients, 14 (41%) were transfusion dependent. There was no significant difference between patients with congenital and acquired neuroimaging findings and patients with normal neuroimaging regarding transfusion dependency. CONCLUSIONS: Acquired abnormalities in brain tissue, such as white matter intensity changes, white matter T2 hyperintense discrete foci, or infarcts along with congenital abnormalities, were identified in this study. Variable abnormal brain imaging findings in FA patients, although some were not associated with clinical neurological manifestations, suggest that brain imaging could be part of screening in FA.

Children with lymphoma presenting with hemophagocytic lymphohistiocytosis.

BACKGROUND: < 7b > Hemophagocytic lymphohistiocytosis (HLH) may precede malignancy, in particular lymphomas and leukemias. However, the causative factors, appropriate treatment and the prognosis of this association is not established. CASE: Herein, we present two patients, one with nodular sclerosing Hodgkin lymphoma (HL) and concomitant Epstein-Barr virus (EBV) infection, and the other with anaplastic large cell lymphoma (ALCL), presented as malignancy associated HLH. CONCLUSION: In our patients, malignancy directed therapy was sufficient to treat HLH symptoms both at presentation and at recurrence in the second patient.

A Rare Malignity of Childhood: Krukenberg Tumor-Case Report and Review of Literature.

Krukenberg tumor (KT) is a rare ovarian carcinoma containing mucin-filled signet ring cells. It accounts for 1%-2% of all ovarian tumors. It is seen at an average age of 40 years. Reported pediatric cases of KT in the literature are very limited. Herein, we present an adolescent with a KT that was compatible with metastatic ring cell colon carcinoma.

Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics.

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

Assessment of Peripheral Neuropathy in Patients with ß-Thalassemia via Electrophysiological Study: Reevaluation in the Era of Iron Chelators.

Peripheral neuropathy is one of the complications of ß-thalassemia (ß-thal) that has been investigated in limited reports. We aimed to detect the rate of peripheral neuropathy and risk factors for neuropathy development in patients with ß-thal. The study was performed in patients with ß-thal intermedia (ß-TI) or ß-thal major (ß-TM). Prospective electrophysiological studies were achieved via standard procedures. A total of 27 patients were enrolled in the study. Electrophysiological studies for both motor and sensory nerves were within normal range. In motor nerve studies, delayed peroneal nerve latency was found in patients with high ferritin levels, increased ulnar nerve amplitude was detected in patients ≥20 years old, and increased tibial nerve amplitude was seen in patients with low copper levels. We could not show peripheral neuropathy in our patients. Increased ferritin level, older age, and copper deficiency may cause mild changes in electrophysiological studies of motor nerves.

Evaluation of Serum Trace Element and Vitamin Levels in Children With Cancer in the First 6 Months After Diagnosis.

Adequate nutrient intake should be provided for the cure of children diagnosed with cancer. The aim of this study was to evaluate serum trace elements and vitamins of children with cancer at diagnosis and during treatment. Children with newly diagnosed cancer who were admitted to our center were evaluated for serum selenium, iron, ferritin, C-reactive protein, vitamin B12, folate, and 25-OH vitamin D levels at presentation, and at the third and sixth months of cancer treatment. Forty-two children (male/female: 15/27) with a median age of 8 years (range, 2 to 17) were included in the study. Mean serum B12, folate, and iron levels were within normal ranges, but selenium and 25-OH vitamin D were low at presentation and during the 6-month period. Serum ferritin levels were high in all 3 measures, but they decreased significantly at the sixth month (P=0.04). There was no relation between micronutrient deficiency and sex, or primary disease, or stage, or place of residence of the patient. In conclusion, serum trace element and vitamin deficiencies are common in children with cancer, and there is a need for further studies with larger patient series.

Molecular genetic analysis of the F11 gene in 14 Turkish patients with factor XI deficiency: identification of novel and recurrent mutations and their inheritance within families.

BACKGROUND: Factor XI (FXI) deficiency is an autosomal bleeding disease associated with genetic defects in the F11 gene which cause decreased FXI levels or impaired FXI function. An increasing number of mutations has been reported in the FXI mutation database, most of which affect the serine protease domain of the protein. FXI is a heterogeneous disorder associated with a variable bleeding tendency and a variety of causative F11 gene mutations. The molecular basis of FXI deficiency in 14 patients from ten unrelated families in Turkey was analysed to establish genotype-phenotype correlations and inheritance of the mutations in the patients' families. MATERIAL AND METHODS: Fourteen index cases with a diagnosis of FXI deficiency and family members of these patients were enrolled into the study. The patients' F11 genes were amplified by polymerase chain reaction and subjected to direct DNA sequencing analysis. The findings were analysed statistically using bivariate correlations, Pearson's correlation coefficient and the nonparametric Mann-Whitney test. RESULTS: Direct DNA sequencing analysis of the F11 genes revealed that all of the 14 patients had a F11 gene mutation. Eight different mutations were identified in the apple 1, apple 2 or serine protease domains, except one which was a splice site mutation. Six of the mutations were recurrent. Two of the mutations were novel missense mutations, p.Val522Gly and p.Cys581Arg, within the catalytic domain. The p.Trp519Stop mutation was observed in two families whereas all the other mutations were specific to a single family. DISCUSSION: Identification of mutations confirmed the genetic heterogeneity of FXI deficiency. Most of the patients with mutations did not have any bleeding complications, whereas some had severe bleeding symptoms. Genetic screening for F11 gene mutations is important to decrease the mortality and morbidity rate associated with FXI deficiency, which can be life-threatening if bleeding occurs in tissues with high fibrinolytic activity.

Heavy metal levels in patients with ineffective erythropoiesis.

OBJECTIVES: Iron is taken into enterocytes at the duodenum via apical divalent metal-ion transporter 1 protein. Besides iron, divalent metal-ion transporter 1 also transports other divalent metals. We aimed to investigate blood heavy metal levels in patients with ineffective erythropoiesis. METHODS: Blood levels of heavy metals including Pb, Al, Cd, Cr, Co, Cu, and Zn were measured in patients with thalassemia major (TM), thalassemia intermedia (TI), congenital dyserythropoietic anemia (CDA), and age- and sex-matched healthy controls. RESULTS: Blood samples were obtained from 68 patients (51 patients with TM, 8 with TI, 9 with CDA), and a control group that included 65 volunteers. Patients with TM were found to have lower Al, Pb, and Zn, and higher Cd levels compared with the control group. The patients treated with deferasirox were further analyzed and Pb and Zn levels were found lower compared with the control group. DISCUSSION: Patients with TM had tendency to have elevated levels of plasma cadmium; however, the median level was not at a toxic level. Increased metal-ion transporter 1 activity may cause heavy metal accumulation, but deferasirox chelation may be protective against heavy metals besides iron.

An orbital perivascular epithelioid cell tumor in a 7-year-old boy: case report and review of the literature.

We report the case of a 7-year-old boy who presented with a swollen right eye. Magnetic resonance imaging revealed a right intraconal orbital mass with intense contrast enhancement. Incisional biopsy led to a diagnosis of perivascular epithelioid cell tumor (PEComa). Sirolimus was initiated but discontinued at the third week of treatment because the tumor had progressed. A minor regression of the tumor was seen after six cycles of systemic chemotherapy. Previously reported cases of PEComa were benign in nature, and full remission was achieved with surgical excision. In the present case the tumor was malignant and responded only slightly to systemic chemotherapy.

The questioning for routine monthly monitoring of proteinuria in patients with ß-thalassemia on deferasirox chelation.

BACKGROUND: Iron chelation therapy is one of the mainstays of the management of the patients with ß-thalassemia (BT) major. Deferasirox is an oral active iron chelating agent. Proteinuria is one of the potential renal adverse effects of deferasirox, and monthly follow-up for proteinuria is suggested by Food and Drug Administration and European Medicine Agency. METHODS: We aimed to investigate the necessity for monthly monitoring for proteinuria among patients with BT on deferasirox. A retrospective laboratory and clinic data review was performed for patients with BT major or intermedia who were treated with deferasirox chelation therapy. All patients were monitored for proteinuria for every 3 or 4 weeks after the initiation of deferasirox with serum creatinine and spot urine protein/creatinine ratios. RESULTS: The median follow-up time of the 37 (36 BT major and one BT intermedia) patients was 44 months. Seven patients (18.9%) developed significant proteinuria (ratio ≥0.8). Of the 1490 measurements, 12 tests (0.8%) were proteinuric. Urine proteinuria resolved in all of the patients during the follow-up. The risk of proteinuria was higher at ages below a cut-off point of 23 years (p = 0.019). Patients, who were on deferasirox at doses above a cut-off dose of 29 mg/kg/day, were found to have higher risk of proteinuria development (p = 0.004). CONCLUSION: Proteinuria resolves without any complication or major intervention according to our results. Potentially more risky groups (age below 23 years old and receivers above a dose of 29 mg/kg/day) might be suggested to be followed monthly, besides monitoring all of the patients.

Sorafenib-induced Posterior Reversible Encephalopathy Syndrome in a Child With FLT3-ITD-positive Acute Myeloid Leukemia.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiologic condition characterized by headache, seizures, impaired vision, acute hypertension, and typical cranial MRI findings. OBSERVATION: A 10-year-old boy with FLT3-ITD-positive acute myelogenous leukemia who developed PRES during sorafenib treatment has been presented here. In English literature, there are 2 adult patients with metastatic cholangiocarcinoma or hepatocellular carcinoma who developed PRES under sorafenib treatment. Our patient is the first pediatric case with the diagnosis of acute myelogenous leukemia who developed PRES that might be attributed to sorafenib use. CONCLUSIONS: Thus, PRES might be a rare, potentially serious, but manageable, side effect of sorafenib that should be kept in mind by pediatric hematologists and oncologists.

Foetal and neonatal intracranial haemorrhage in term newborn infants: Hacettepe University experience.

In this study, we aimed to evaluate the incidence, risk factors, causes and clinical management of intracranial haemorrhage (ICH) diagnosed during foetal life or in the first month of life in term neonates with a discussion of the role of haematological risk factors. This study included term neonates (gestational age 37-42 weeks) with ICH diagnosed, treated and followed up in the Neonatal Intensive Care Unit of Hacettepe University, Ankara, Turkey, between January 1994 and January 2014. Medical follow-up was obtained retrospectively from hospital files and prospectively from telephonic interviews and/or clinical visits. During the study period, 16 term neonates were identified as having ICH in our hospital. In six (37.5%) neonates, ICH was diagnosed during foetal life by obstetric ultrasonography, and in 10 (62.5%) neonates, it has been diagnosed after birth. Haemorrhage types included intraventricular haemorrhage (IVH) in eight (50.0%), intraparenchymal haemorrhage in six (37.5%), subarachnoid haemorrhage in one (6.2%) and subdural haemorrhage in one (6.2%) neonate. IVH was the most common (n = 5/6, 83.3%) haemorrhage type among neonates diagnosed during foetal life. Overall, haemorrhage severity was determined as mild in three (18.7%) neonates, moderate in three (18.75%) neonates and severe in 10 (62.5%) neonates. During follow-up, one infant was diagnosed as afibrinogenemia, one diagnosed as infantile spasm, one cystic fibrosis, one orofaciodigital syndrome and the other diagnosed as Friedrich ataxia. Detailed haematological investigation and search for other underlying diseases are very important to identify the reason of ICH in term neonates. Furthermore, early diagnosis, close monitoring and prompt surgical interventions are significant factors to reduce disabilities.