Zeynep Canan Özdemir

Beta blocker and steroid therapy in the treatment of infantile hepatic hemangioendothelioma

Infantile hepatic hemangioendothelioma (IHHE) is the most common benign vascular liver tumor and typically occurs during the first 6 months of life. A 4-month-old male patient presented with abdominal distention. A physical examination revealed massive hepatomegaly. Liver enzyme levels were normal. The alpha fetoprotein level was 1,323 mg/dL (6-1,000). Abdominal magnetic resonance imaging (MRI) showed multiple, well-defined and hyperintense nodular lesions in the liver. MRI findings suggested IHHE. The thyroid stimulating hormone (TSH) level was high (177.2 µU/mL). He was started on sodium levothyroxine 50 μg daily. The patient has hypoxemia due to abdominal distention during the follow-up period. Oral methylprednisolone therapy was started at a dose of 2.5 mg/kg/dose, and propranolol at a dose of 1 mg/kg/dose, bid. Fifteen days later his TSH level remained elevated at 212.3 μU/mL despite repeatedly increasing the dose of levothyroxine up to 200 μg/daily. One month after the initial presentation, his TSH level was reduced to 11.28 µU/mL. We observed a marked improvement in abdominal distention and respiratory distress within 15 days and an average reduction of 50% in the lesion diameters after a month. Despite its benign nature, IHHE may lead to development of complications. Steroid and propranolol treatment may be useful in in the management of emergency complications.

Is N-acetylcysteine infusion an effective treatment option in L-asparaginase associated hepatotoxicity?

Fig. 1. Abdominal computed tomography showed a hepatomegaly and hepatosteatosis. REFERENCES 1. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054-61. 2. Scott LM. The JAK2 exon 12 mutations: a comprehensive review. Am J Hematol 2011;86:668-76. 3. Darwish Murad S, Plessier A, Hernandez-Guerra M, et al. Etiology, management, and outcome of the Budd-Chiari syndrome. Ann Intern Med 2009;151:167-75. 4. Milosevic Feenstra JD, Nivarthi H, Gisslinger H, et al. Wholeexome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms. Blood 2016;127: 325-32. 5. Alghasham N, Alnouri Y, Abalkhail H, Khalil S. Detection of mutations in JAK2 exons 12-15 by Sanger sequencing. Int J Lab Hematol 2016;38:34-41.

The frequency of hepatotoxicity and myelotoxicity in leukemic children with different high doses of methotrexate

Background and objectives Methotrexate (MTX) is a chemotherapeutic agent that functions as a folic acid antagonist. The frequency of high dose methotrexate (HDMTX)-associated toxicity is variable. In this study, we investigated the frequency of myelotoxicity and hepatotoxicity 7 days after HDMTX infusion. Patients and methods This study included children diagnosed with acute lymphoblastic leukemia (ALL) between January 2010 and April 2015. The patient blood counts and biochemical parameters measured before and after 7 days of HDMTX infusion were retrospectively recorded. We assessed HDMTX infusions for 48 children. The number of patients and drug doses included the following: 17 children receiving 1 g/m2 (68 infusions), 14 children receiving 2 g/m2 (56 infusions), and 17 children receiving 5 g/m2 (68 infusions). The classification of toxicity was made based on the Common Terminology Criteria for Adverse Events (CTCAE) 2010 criteria. Myelotoxicity was defined as a hemoglobin level <10 g/L and absolute neutrophil count <1 × 109/L or platelet count <75 × 109/L. The presence of transaminase levels ≥5 times the upper limit was considered to be hepatotoxicity grade ≥3. The MTX levels at 42 h in patients with and without toxicity were compared to evaluate the correlation between MTX levels, hematologic parameters, and transaminase levels. Results Myelotoxicity was observed in 35.2%, 37.5%, and 33.8% of the infusions, and hepatotoxicity grade ≥3 was detected in 13.2%, 12.5%, and 11.7% of the infusions in patients receiving 1, 2 and 5 g/m2 HDMTX after 7 days, respectively. There was no statistically significant difference between MTX levels at 42 h in patients with and without toxicity (P > .05, for all). There was no correlation between hematologic parameters and transaminase levels and MTX levels at 42 h. Conclusion Hematologic toxicity was the most common toxicity observed. The data indicate the hematologic toxicity increased after repeated cycles in patients receiving 5 g/m2. However, the hepatic toxicity decreased with additional cycles. Our results show the level of MTX at 42 h is not effective to identify toxicity.

The association of ghrelin, leptin, and insulin levels in umbilical cord blood with fetal anthropometric measurements and glucose levels at birth

Abstract Objectives: To investigate the association of ghrelin, leptin, and insulin levels in the umbilical cord blood of the preterm and term infants with anthropometric measurements and glucose metabolism. Methods: Sixty-nine infants who were born between November 2004 and June 2005 were included in the study. Pregnancy ages, birth weights, heights, head circumferences, and Ponderal Indexes (PI) were identified. Ghrelin, leptin, insulin, and glucose levels in the umbilical cord blood were studied. Results: Eighteen infants out of 69 infants were preterm (34.6 ± 0.43 weeks), and 33 infants were term (38.7 ± 0.14 weeks). All preterm infant weights were appropriate for gestational age (AGA); 33 of the term infants’ weights were AGA and 18 were large for gestational age (LGA). Leptin, insulin, and glucose levels of term infants were significantly higher compared with the preterm infants (p < .0001, p < .001, and p < .0001, respectively); no significant difference was detected in the ghrelin levels between the two groups (p > .05). The leptin and insulin levels of the term LGA infants were higher compared with the term AGA and preterm AGA infants (p < .05, for all). No difference was detected between the three groups regarding serum ghrelin levels (p > .05). No difference was found in the glucose levels between term AGA and LGA infants (p > .05); however, the serum glucose levels of term AGA and LGA infants were higher compared with levels in preterm AGA infants (p < .05, for both). A positive correlation was demonstrated in all study groups between leptin and insulin with gestational age, body weight, height, head circumference, and PI. A positive correlation was found between serum leptin levels with gestational age and insulin levels in preterm infants, and between serum leptin levels and insulin and glucose levels in term infants. No association was found between ghrelin and anthropometric measurements, leptin, insulin, and glucose levels (p > .05, for all). Conclusions: The increase of leptin production with increased gestational age, and the strong association with anthropometric measurements supports the opinion that leptin behaves as a fetal growth factor. Leptin in intrauterine life is in close association with insulin and glucose metabolism. Although ghrelin was at measurable levels in preterms, no association with fetal growth and glucose metabolism could be demonstrated in preterm and term infants.

Evaluation of hypercoagulability with rotational thromboelastometry in children with iron deficiency anemia

ABSTRACT Objective: Iron deficiency anemia (IDA) has been demonstrated to be a risk factor for thromboembolic events, although the pathogenesis of the development of thromboembolism in IDA is as yet unclear. The likelihood of children with IDA contracting hypercoagulability was evaluated in this cross-sectional study using rotational thromboelastometry (ROTEM). Material and Method: A total of 57 children with IDA (median age 11 years; 37 female, 20 male) and 48 healthy children (median age 9.9 years; 23 female, 25 male) were enrolled in the study. Whole blood count, serum iron, transferrin saturation, ferritin level, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen levels were ascertained, while ROTEM assays [intrinsic TEM (INTEM) and extrinsic TEM (EXTEM)] were used to measure and analyze coagulation time (CT), clot formation time (CFT), maximum clot firmness (MCF) and rate of maximum lysis (ML60%). This study conforms to ethical standards, has been approved by the appropriate Institutional Review Board. Results: Hemoglobin, serum iron, transferrin saturation and ferritin levels were lower in the IDA group than in the control group (p < 0.001, for all), while the EXTEM and INTEM CT in the two groups were similar (p > 0.05). The EXTEM and INTEM MCF in the IDA group was higher than in the control group, while the INTEM CFT and rate of ML60% were lower than in the control group (p < 0.001, p < 0.001, p < 0.05, p < 0.001, respectively). Conclusion: The ROTEM results suggest that although the platelet count and coagulation tests were within normal ranges in IDA, the tendency to coagulate may have been increased.

Plasmapheresis in a child with cold antibody autoimmune hemolytic anemia: case report

Autoimmune hemolytic anemia is a picture of hemolysis which is caused by autoantibodies against red blood cell surface antigens. It is classified as primary, secondary or warm and cold autoimmune hemolytic anemia according to the temperature at which antibodies react. It is usually an acute and self-limiting condition. Here, we present a three-year-old male patient who presented with malaise, paleness, and dark-colored urine. His hemoglobin level was 5.8 g/dL, and increased indirect bilirubin and lactate dehydrogenase levels and decreased haptoglobulin and reticulocyte levels were noted. A direct Coombs test was positive using anti-C3. Four erythrocyte suspension transfusions were given because the anemia was life-threatening. High-dose steroids (30 mg/kg/ day, methylprednisolone) and intravenous immunoglobulin (1 g/kg/day, two days) treatments were unresponsive. Plasmapheresis was performed and no further transfusions were needed after plasmapheresis. Plasmapheresis treatment can be effective in children with cold type autoimmune hemolytic anemia.

Evaluation of febrile neutropenic attacks of pediatric hematology-oncology patients with febrile neutropenia

Aim Febrile neutropenia is an important cause of mortality and morbidity in hematology-oncology patients undergoing chemotherapy. The objective of this study was to evaluate febrile neutropenic episodes in children with malignancy. Material and Methods Sixty-eight children who received chemotherapy for malignancy between 2010 and 2015 were retrospectively reviewed. The demographic characteristics, laboratory data, infection foci, and frequency of microorganisms grown in culture were examined. Also, the frequency of febrile neutropenic attacks was investigated according to the chemotherapy periods. Results Of the total 200 episodes, 81 (40.5%) were clinically documented, and 73 (36.5%) were microbiologically documented infections. Fever of unknown origin was observed in 46 (23%) episodes. The most frequently clinically documented focus were mucositis (33.4%) and pneumonia (24.7%). Blood culture was positive in 55 (75.3%) episodes of microbiologically documented infections. The most commonly isolated microorganisms in blood culture were Gram-negative bacteria (47.2%). C-reactive protein levels in microbiologically documented infections were higher than in clinically documented infections, and fever of unknown origin (p<0.05, for both). The most common underlying malignancy was acute lymphoblastic leukemia (73.5%). The highest proportions (34.6%) of febrile neutropenic episodes were observed during the reinduction period for these children. Nine (13.2%) children died of neutropenic sepsis. Conclusions Febrile neutropenia continues to be an important cause of mortality in pediatric patients with malignancy. C-reactive protein levels may be an indicator for predicting bacterial infection in children with febrile neutropenia without apparent focus. The most frequently isolated agents in our center were Gram-negative microorganisms. Determining the microbial flora of each center may be beneficial to improving survival rates.

Fatal course of Saprochaete capitata fungemia in children with acute lymphoblastic leukemia

ABSTRACT Saprochaete capitata (S. capitata) is a very rare fungal pathogen that causes disseminated opportunistic infections in patients with hematologic malignancies. Fever resistant to broad-spectrum antibiotic and antifungal treatment is common in the presence of fungemia during the period of profound neutropenia. We describe three cases of leukemic children who died from S. capitata fungemia following a first febrile neutropenic episode after the induction of chemotherapy. S. capitata fungemia is an emergent infection associated with high mortality and low susceptibility to fluconazole and echinocandins. Awareness of this emergent infection is needed to ensure that it can be properly treated.

Incomplete Miller—Fisher syndrome with advanced stage Burkitt lymphoma

BackgroundLymphoma-associated incomplete Miller-Fisher syndrome is very rare.Case CharacteristicsAn 11-year-old boy who initially presented with headache, left ptosis, diplopia and weakness. Neurologic examination indicated left sided ptosis with ophthalmoplegia.ObservationsCerebral imaging and cerebrospinal fluid examinations were normal. Magnetic resonance imaging of the abdomen showed a mass lesion in the ileal loops. A bone marrow biopsy showed infiltration by Burkitt’s lymphoma.MessageBurkitt lymphoma may present with incomplete Miller Fisher syndrome.

Treatment with propranolol for infantile hemangiomas: single-center experience.

Infantile hemangiomas (IHs) are the most common soft tissue tumors of infancy. Although spontaneous regression is expected, medical treatment is needed in approximately 10–20% of cases.