Serdar Özkasap

The Role of Prohepcidin in Anemia Due to Helicobacter pylori Infection

Background: Hepcidin, a key regulator of iron homeostasis, increases when inflammation and some infections occur. It plays a critical role in macrophage iron retention, which underlies inflammation/infection caused anemia. It is known that Helicobacter pylori (HP) may lead to iron deficiency (ID) due to occult blood loss or reduced iron absorption. This study investigates the role of prohepcidin, hepcidins precursor, in ID and ID anemia (IDA) with a concurrent HP infection. Methods: In this prospectively designed study, 15 patients with IDA and a concurrent HP infection (group 1), 11 patients with an ID and a concurrent HP infection (group 2), and 18 patients with HP infection (group 3) were observed. All groups received only HP eradication therapy. Twenty-five age- and sex-matched children without ID/IDA and HP infection were included in the study as the control group. In all groups and control group, measurements were taken for pre- and posttreatment hemoglobin, serum prohepcidin, serum ferritin, serum iron (SI), transferrin saturation, erythrocyte sedimentation rate, fibrinogen, and C-reactive protein levels. Results: The pretreatment prohepcidin levels were significantly higher only in group 1 compared to the control group (P < .05). In group 1, a significant increase in hemoglobin and SI levels and a significant reduction in prohepcidin levels were additionally observed following HP eradication treatment (P < .05). However, in groups 2 and 3, significant differences in hemoglobin, iron, and prohepcidin levels between pre- and posttreatment were not observed. Conclusion: Elevated serum prohepcidin might indicate the role of inflammation in the etiology of anemia concurrent with HP.

ACUTE RENAL FAILURE DURING ATRA TREATMENT

All-trans-retinoic acid (ATRA), which is used in acute promyelocytic leukemia, is usually well tolerated, but some side effects can be observed. Retinoic acid syndrome is the most severe side effect. Triazole derivatives such as fluconazole inhibit the NADPH-dependent cytochrome P-450-mediated catabolism of ATRA and are increased plasma levels of ATRA. Here, the authors report a case of APL who developed acute renal failure during ATRA and concurrent use of fluconazole.

Deferasirox therapy in children with Fanconi aplastic anemia.

Thirty-nine children with Fanconi aplastic anemia (FAA) have been followed up in our center between January 2008 and November 2010. Eight of these children (20%) with a transfusional iron overload had been undergoing deferasirox treatment during the study period. In the English literature, transfusional iron overload and the use of an iron chelator in children with FAA has not yet been evaluated. Here, we have presented the effectivity and tolerability of deferasirox in children with FAA and a transfusional iron overload. Before the deferasirox treatment, the mean serum ferritin level was 3377±2200 ng/mL. After a mean 13.6-month treatment duration, the mean ferritin level decreased to 2274±1300 ng/mL (P<0.05). In our series, 3 patients had renal and 3 had hepatic toxicity during the treatment. Two patients had peliosis hepatis and 2 had congenital renal abnormalities before the treatment. There may be differences in the side-effect profiles of deferasirox treatment in patients with FAA. In our series, despite the low number of cases, nephrotoxicity and hepatotoxicity were common side effects instead of gastrointestinal disturbances reported in other studies. Deferasirox is an oral, easily applicable, and effective iron chelator; baseline hepatotoxicity and nephrotoxicity may increase the development of toxic side effects in children with FAA. Patients with FAA receiving deferasirox treatment should be followed up closely for these side effects.

Endocrinopathies in Turkish children with Beta thalassemia major: results from a single center study.

The endocrinological complications in β-thalassemia major patients do affect the life quality to a large extend. In this study, the endocrinological complications of 47 β-thalassemia patients, who have been followed-up at our hospitals pediatric hematology department, were evaluated. Out of β-thalassemia major cases included to this study, the 55.3% was male and 44.7% was female. The patients’ mean levels of ferritin, whose mean age was 10.0 ± 4.5 years (2–20 years), were 2497 ± 1469 ng/mL (472–8558 ng/mL). At least one endocrinological pathology in 27 out of 47 (57.4%) and more than one endocrinological pathology in 14 out of 47 (29.7%) thalassemia patients were observed. The most frequently observed complication in followed-up cases was vitamin D insufficiency and deficiency (78.2%). The other complications in decreasing order were pubertal failure (41.6%), growth retardation (25.5%), decreased bone-mineral density (22.2%), secondary hyperparathyroidism (11.5%), overt hypothyroidism (4.25%), subclinical hypothyroidism (2.12%), and impaired glucose tolerance (2.12%). There was no statistically significant difference between serum mean ferritin level and endocrin complications (P > .05). Four patients (8.5%) had decreased signal intensity in pituitary magnetic resonance imaging (MRI) but this finding was not associated with ferritin levels (P = .87). MRI parameters were similar between patients with and without gonadal dysfunction. Mean height of the pituitary gland was 4.98 ± 1.1 mm (3–9 mm) and this was similar to those normal values in the literature. Ferritin levels were not correlated with pituitary height (P > .05). Beta thalassemia major, having the potential of leading to multisystemic complications, is a chronic disease that should be treated and followed-up by a multidisciplinary approach. Due to frequently encountered endocrinological complications, beta thalassemic patients should be followed-up regularly by hematology and endocrinology departments in coordination.

Leptin promoter G-2548A genotypes and associated serum leptin levels in childhood acute leukemia at diagnosis and under high-dose steroid therapy.

Abstract Genotype/allele distributions of leptin promoter G−2548A polymorphism, serum leptin and insulin levels and body weight were not significantly different between 72 children (39 male/33 female; age range 1.08–16, median 6 years) with acute leukemia (56 acute lymphoblastic leukemia [ALL]/16 acute non-lymphoblastic leukemia [ANLL]) at diagnosis and 70 age- and sex-matched controls (p > 0.05). The − 2548GG genotype was associated with the highest leptin levels in controls and patients with acute leukemia after 7-day high-dose methylprednisolone (HDMP) therapy (p < 0.05), while no significant association of genotype with leptin levels was detected in patients at diagnosis (p > 0.05). One-week HDMP therapy in patients carrying the − 2548G allele caused a significant increase in leptin levels and body weight (p < 0.001), whereas increases in those carrying the − 2548AA genotype were insignificant (p > 0.05). Decreases in white blood cell counts of patients after therapy were insignificant in − 2548GG (p > 0.05) yet significant in − 2548GA and − 2548AA (p < 0.05) genotypes. These results revealed no association of leptin genotype with the etiology of childhood acute leukemia but a possible association with leptin levels and effects of HDMP therapy.

Difficulties in the treatment of an Infant with Hemophilia B

Dear Editor, Hemophilia B is a X-linked recessive bleeding disorder which occurs as a result of Factor IX (FIX) deficiency (1, 2). In some patients with hemophilia, antibody (inhibitor) and allergic reaction may develop against FIX protein which is administered for treatment (3). While antibody develops against the factor administered in approximately 15–25% of the patients with severe hemophilia A, this rate is much lower in patients with hemophilia B (3%). Life-threatening allergic reactions may develop in 50% of the patients who have inhibitor (4). There is no efficient treatment which can be used to prevent allergic reaction developing secondary to antibody response. In this case report, the difficulties in treatment of an infant with severe hemophilia B who developed antibody and allergic reaction against FIX treatment have been discussed. Our patient was diagnosed with hemophilia B after investigations performed because of severe hemorrhage which developed following circumscision at the age of five months. At presentation, the bleeding tests revealed an activated partial thromboplastin time (aPTT) of 104 seconds and a FIX level of 1%. A concentrate containing FIX protein obtained from 9 doses of plasma was used to stop bleeding. When the patient was 14-month old, he was rehospitalized because of head trauma. His cranial ultrasonography and brain tomography findings were found to be normal. FIX concentrate (Replenine®) was initiated at a dose of 80 IU/kg by way of slow intravenous infusion because of head trauma. However, anaphylactic reaction (diffuse urticaria, blushing in the face, cough, dyspnea, cyanosis) developed during infusion of factor concentrate. Dexamethasone, antihistaminic and adrenaline were administered for treatment. In the following administrations, his treatment was switched to Berinine® which is another FIX concentrate with prophylactic administration of antihistaminic and steroid. A similar anaphylactic reaction developed in the third minute of infusion of this new concentrate and treatment was immediately discontinued. Antihistaminic, dexamethasone and adrenaline were administered again. In the follow-up visit one month later, aPTT was found to be 134 s, the FIX level was found to be 0.1% and the amount of inhibitor was found to be 1.7 BU. As a result of mutation study, CGA>TGA (R252X) mutation was demonstrated in exon 8, n.30875, codon 252. Non-human-derived recombinant active FVIIa (rFVIIa - Novo Seven®) was given for severe bleedings in the following periods because of development of antibody. Allergic reaction may occur against FIX protein in patients with hemophilia B who have developed antibody in contrast to hemophilia A (5). Follow-up and treatment of hemorrhage is difficult in patients with hemophilia who are allergic against external FIX protein and develop FIX-related antibody. Antibodies are involved in morbidity and mortality related with bleeding. FIX concentrates are not appropriate, because these patients develop antibody and allergy against FIX concentrates. Since treatment with active prothrombin complex concentrate (aPCC) involves FIX, it may result in allergic reaction similarly (6). Development of recombinant FVIIa provided an appropriate treatment option for patients with hemophilia who develop inhibitor. However, no consensus has been made in relation with treatment with aPCC and rFVIIa in FIX patients who have developed antibody (7). In our own individual experience, it was observed that hemostasis control was provided with aPCC treatment during surgery in patients with hemophilia B who developed antibody (8). It should be kept in mind that the cost of recombinant FVIIa concentrates is high and they carry a risk of thrombosis. Therefore, inhibitor elimination and desensitization treatment should be considered in these patients (9). Elimination of antibody is considerably difficult and treatment success is poor in patients with hemophilia B who are allergic against Factor IX concentrates and who develop antibody. Immune tolerance induction (ITI) treatment which is commonly used in patients with hemophilia A to eliminate antibody and is successful is generally ineffective in these patients. It is recommended that patients with high-risk in terms of development of antibody (patients with complete gene loss) should be identified with molecular analyses at the time of first diagnosis and monitored closely in the beginning of treatment (5). In patients with hemophilia B, it is recommended that the first 10–20 treatments should be administered in hospital in terms of allergy and family members should be trained in terms of the risk of anaphylaxis (10). In conclusion, we aimed to emphasize the difficulties in follow-up of patients with severe hemophilia B who develop allergic reaction and inhibitor against FIX concentrates. Since life-threatening allergic reactions against Factor IX concentrates may develop, the initial administrations in treatment of patients with newly diagnosed hemophilia B should be definitely performed in hospital environment. Recombinant FVIIa is the only appropriate option for treatment of hemorrhage in these patients. Despite a need for inhibitor elimination and desensitization treatment, there is no current application in this area and further studies are needed.

Urinary retention in acute lymphoblastic leukemia induction therapy: Two distinct pathologies

Intrathecal chemotherapy and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system disease in hematologic malignancies. We presented two children with urinary retention due to neurotoxicity with two distinct drugs and reasons. The main presenting complaints were urinary retention and incontinence in both patients. Before the adverse clinical event, the patients had received vincristine intravenously and triple therapy with hydrocortisone, cytosine arabinoside, and methotrexate intrathecally. The clinical event resolved, and vincristine and intrathecal chemotherapy were deleted from the patients subsequent therapy until recovery was achieved.

Kidney growth and renal functions under the growth hormone replacement therapy in children

Abstract Objective: The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. Materials and methods: A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Results: Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p < 0.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p < 0.05). Height was the most significant predictor of kidney volume in rhGH received children (p < 0.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p < 0.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p > 0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (p < 0.05). Conclusions: In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.