Publications by authors named "Aytemiz Gurgey"

90 Publications

Cohort Study: Central Venous Catheter-Related Complications in Children with Hematologic Diseases at a Single Center.

Turk J Haematol 2015 Jun;32(2):144-51

Afyon Kocatepe University Faculty of Medicine Hospital, Department of Pediatrics, Afyonkarahisar, Turkey Phone: +90 (272) 246 33 33 E-mail:

Objective: This study aims to document and analyze the central venous catheter (CVC)-related complications in children with hematological diseases who were treated within a single institution.

Materials And Methods: A retrospective investigation was conducted in 106 pediatric patients in whom 203 CVCs were inserted. A total of 175 catheter-related complications occurred in 5 years.

Results: The rates of clinical catheter infections, local catheter infections, venous thromboembolism, bleeding, and mechanical complications were 2.6, 1.1, 0.2, 0.2, and 0.2 per 1000 catheter days. Methicillin-resistant Staphylococcus epidermidis was the predominant infectious organism in blood and catheter cultures. The children with leukemia had a significantly higher frequency of clinical catheter infections (p=0.046). The children who underwent bone marrow transplantation had a significantly lower frequency of clinical catheter infections (p=0.043) and higher frequency of local catheter infections (p=0.003). The children with implanted catheters had a significantly lower frequency of clinical catheter infections (p=0.048). The children with thrombocytopenia had significantly fewer local catheter infections and significantly more clinical catheter infections and catheter-related bleeding (respectively p=0.001, p=0.042, and p=0.024).

Conclusion: Leukemia, bone marrow transplantation, and thrombocytopenia are risk factors for CVC-associated complications. The relatively higher number of interventions performed via permanent catheters may be responsible for the significantly increased incidence of systemic infections and mechanical injury.
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http://dx.doi.org/10.4274/tjh.2013.0403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451482PMC
June 2015

Congenital thrombotic thrombocytopenic purpura with novel mutations in three unrelated Turkish children.

Pediatr Blood Cancer 2014 Mar 30;61(3):558-61. Epub 2013 Sep 30.

Division of Pediatric Immunology and Allergy, Ankara Children's Hematology Oncology Training and Research Hospital, Ministry of Health, Ankara, Turkey.

Congenital thrombotic thrombocytopenic purpura (TTP) is an inherited disease caused by mutations in the ADAMTS 13 gene and has been reported to have diverse ages of presentation, ranging from the newborn period to adulthood. Herein, we present three cases of congenital TTP who were symptomatic during childhood (neonatal period, 7 and 10 years) and were each initially given different diagnoses. Congenital TTP was later diagnosed by molecular analysis and responsiveness to fresh frozen plasma. Three novel mutations in a homozygous state were identified in these patients: c.1308G>C, c.428T>C (p.Ile143Thr) and c.1709A>G (p.Tyr570Cys).
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http://dx.doi.org/10.1002/pbc.24764DOI Listing
March 2014

Defective UNC13D gene-associated familial hemophagocytic lymphohistiocytosis triggered by visceral leishmaniasis: a diagnostic challenge.

J Pediatr Hematol Oncol 2014 Jan;36(1):e42-5

*Department of Pediatric Hematology, Faculty of Medicine, Hacettepe University †Department of Pediatric Hematology, Ankara Children's Hematology Oncology Hospital, Dişkapi, Ankara, Turkey.

Background: Visceral leishmaniasis (VL) triggered genetic hemophagocytic lymphohistiocytosis (HLH) is clinically challenging.

Observations: One-year-old VL-HLH patient improved after liposomal-amphotericin-B therapy, but subsequently deteriorated, although bone marrow amastigotes disappeared. Symptoms resolved after 8 weeks of HLH-2004 therapy but recurred upon cessation. Homozygous UNC13D gene 627delT mutation was identified however stem cell donor was unavailable. The patient died at age 4 years after central nervous system attacks and HLH recurrences.

Conclusions: VL in HLH patients does not exclude a genetic etiology and requires structured clinical management. VL should be excluded in all HLH patients in endemic regions before immunochemotherapy, which is recommended for VL-HLH patients unresponsive to VL treatment and/or reactivated.
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http://dx.doi.org/10.1097/MPH.0b013e31829b7f22DOI Listing
January 2014

Structural and functional analysis of perforin mutations in association with clinical data of familial hemophagocytic lymphohistiocytosis type 2 (FHL2) patients.

Protein Sci 2013 Jun;22(6):823-39

Center for Computational Biology and Bioinformatics, College of Engineering, Koc University, Rumelifeneri Yolu, Sariyer, Istanbul, Turkey.

Perforin plays a key role in the immune system via pore formation at the target cell membrane in the elimination of virus-infected and transformed cells. A vast number of observed mutations in perforin impair this mechanism resulting in a rare but fatal disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL2). Here we report a comprehensive in silico structural analysis of a collection of 76 missense perforin mutations based on a proposed pore model. In our model, perforin monomers oligomerize having cyclic symmetry in consistent with previously found experimental constraints yet having flexibility in the size of the pore and the number of monomers involved. Clusters of the mutations on the model map to three distinct functional regions of the perforin. Calculated stability (free energy) changes show that the mutations mainly destabilize the protein structure, interestingly however, A91V polymorphism, leads to a more stable one. Structural characteristics of mutations help explain the severe functional consequences on perforin deficient patients. Our study provides a structural approach to the mutation effects on the perforin oligomerization and impaired cytotoxic function in FHL2 patients.
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http://dx.doi.org/10.1002/pro.2265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690721PMC
June 2013

Recurrent macrophage activation syndrome associated with heterozygous perforin W374X gene mutation in a child with systemic juvenile idiopathic arthritis.

J Pediatr Hematol Oncol 2013 Jul;35(5):e205-8

Division of Pediatric Hematology, School of Medicine, Hacettepe University, Ankara, Turkey.

Background: Recurrent macrophage activation syndrome (MAS) is rarely reported.

Aim: To describe recurrent MAS in a 2.5-year-old girl with systemic juvenile idiopathic arthritis and heterozygous perforin mutation, which may have a role in the patient's first recurrence despite use of the HLH-2004 treatment protocol.

Observations: In the presented case, MAS was initially controlled after the addition of etoposide to the treatment regimen. However, recurrence occurred 6.5 months after cessation of the HLH-2004 protocol. Subsequent recurrences may have occurred because of the family's noncompliance with treatment.

Conclusions: The patient's extremely high serum ferritin level (267,054 ng/mL) and the recurrent course of MAS may have been because of the coexistence of juvenile idiopathic arthritis and heterozygous perforin W374X mutation. We suggest to search for mutations in HLH genes in recurrent MAS cases.
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http://dx.doi.org/10.1097/MPH.0b013e31827b4859DOI Listing
July 2013

Association of nonimmune hydrops fetalis with familial hemophagocytic lymphohistiocytosis in identical twin neonates with perforin His222Arg (c665A>G) mutation.

J Pediatr Hematol Oncol 2013 Nov;35(8):e332-4

*Department of Pediatrics, Division of Hematology, Faculty of Medicine, Hacettepe University, Ankara †Department of Pediatrics, Neonatology Intensive Care Unit, Zeynep Kamil Maternity and Children's Education and Training Hospital, Istanbul, Turkey.

Background: This is the first study demonstrating that nonimmune hydrops fetalis (NIHF) in identical twin neonates is associated with biallelic gene defect causing familial hemophagocytic lymphohistiocytosis.

Observations: Preterm male twins (31(4/7) wk) with NIHF and hepatosplenomegaly gradually developed pancytopenia, hyperferritinemia, hyponatremia, hypoalbuminemia, and elevated alanine aminotransferase, aspartate aminotransferase, bilirubin, and lactate dehydrogenase levels. Suspected sepsis led to antibiotic therapy. Upon detection of hemophagocytosis in bone marrow, multiorgan failure and pulmonary bleeding led to death. Homozygous His222Arg (c665A>G) mutation was identified in Perforin.

Conclusions: Familial hemophagocytic lymphohistiocytosis should be considered in first days of NIHF cases to have chance for HLH-2004 therapy. Missense mutations of Perforin codon His222 may lead to intrauterine presentation.
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http://dx.doi.org/10.1097/MPH.0b013e31827078c6DOI Listing
November 2013

Recurrent pediatric thrombosis: the effect of underlying and/or coexisting factors.

Blood Coagul Fibrinolysis 2012 Jul;23(5):434-9

Hacettepe University, School of Medicine, Department of Pediatric Hematology, Ankara, Turkey.

The objective of this study was to evaluate the underlying diseases, thrombus localization, and other risk factors in pediatric patients with recurrent thrombosis in order to obtain a sense of early awareness of the possible recurrences. We retrospectively evaluated both inherited and acquired thrombophilic risk factors in children with recurrent thrombosis that were diagnosed and treated at Hacettepe University, School of Medicine, Department of Pediatric Hematology, Ankara, Turkey. Both congenital and acquired risk factors associated with recurrent thrombosis, and treatment modalities were analyzed in detail. Among 569 children with thrombosis, 32 (5.6%) presented with recurrent thrombosis. Median age at first presentation in these 32 patients [11 women (34.4%) and 21 men (65.6%)] was 132 months. In all, 29 (90.6%) of the 32 patients had an underlying chronic disorder: the most common of which was congenital heart disease [n = 11 (34.4%)]. At presentation intracardiac localization, including the entrance of the inferior and superior vena cava, was observed in 10 of the patients (31.2%). Thrombosis recurred at the same location in 15 (47%) patients and at a different location in 17 (53%). Median time interval between the first and second episode of thrombosis was 6.5 months (range: 1-180 months). Considering both acquired and congenital thrombophilic factors, three (9.3%) patients, four (12.5%) patients, and 14 (43.8%) patients had five, four, and three risk factors, respectively. More than half of the patients had elevated plasma FVIII (>150 IU/dl) and D-dimer (>0.5 mg/ml) levels. Thrombectomy was performed in three patients with organized, chronic intracardiac thrombus. Tissue plasminogen activator (t-PA) was used more frequently to treat recurrence than the first event (15.6 vs. 28.1%) and consequently the complete resolution rate was higher (40 vs. 77.7%) at the second event. Thrombi partially resolved in 11 of the patients during the initial episode and in 10 patients during recurrence (34 vs. 32%). In all, 29 (87.5%) patients were using prophylaxis at the time of recurrence. [coumadin (n = 16), low molecular weight heparin (n = 12) and aspirin (n = 1)]. In total, four patients (12.5%) died because of their underlying disorders and six (18.7%) developed postthrombotic syndrome during the follow-up. Recurrent thrombosis should be expected, especially in cases with congenital heart disease, incomplete thrombus resolution, and elevated plasma FVIII/D-dimer levels. In the light of this knowledge we suggest aggressive treatment for pediatric patients with a high risk of recurrent thrombosis.
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http://dx.doi.org/10.1097/MBC.0b013e3283548e39DOI Listing
July 2012

A rare metabolic complication of acute lymphoblastic leukemia in childhood: lactic acidosis.

Turk J Pediatr 2012 Jan-Feb;54(1):61-3

Unit of Pediatric Hematology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

A 13-year-old boy presented with nausea, fatigue, weight loss, and bone pain for two months. Complete blood count and serum renal and liver function tests were all normal. Blood gas analysis revealed severe metabolic acidosis with high anion gap. Lactate level was 61.2 mmol/L. Abdominal ultrasonography yielded bilateral nephromegaly and hepatomegaly with increased echogenicity. Peripheral blood smear revealed 2% blasts. Bone marrow aspiration showed 'Common ALL Antigen'-negative acute lymphoblastic leukemia by flow cytometric analysis. Metabolic acidosis dissolved as soon as chemotherapy was begun. Lactic acidosis at the presentation of acute lymphoblastic leukemia--especially with low tumor burden--is a very rare and almost always fatal complication. Our patient is still alive and in remission, which is a point of interest in this child.
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April 2012

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

Leuk Lymphoma 2012 Apr 25;53(4):648-53. Epub 2011 Nov 25.

Division of Hematology, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, Turkey.

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.
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http://dx.doi.org/10.3109/10428194.2011.626881DOI Listing
April 2012

The frequency of A91V in the perforin gene and the effect of tumor necrosis factor-α promoter polymorphism on acquired hemophagocytic lymphohistiocytosis.

Turk J Haematol 2011 Jun;28(2):125-30

Objective: Numerous acquired etiological factors, such as infections, malignancies, and collagen tissue disorders, are involved in the development of acquired hemophagocytic lymphohistiocytosis (AHLH). Not everyone with the same etiological factors developments AHLH, which suggests the role of additional genetic or environmental predisposing factors that remain to be identified.

Methods: Perforin gene A91V missense transition (C>T change at position 272 in exon 2 of the perforin gene) and TNF-α gene promoter-1031 T>C nucleotide substitution are 2 candidate genetic predisposing factors due to their potential to alter inflammatory responses. In the present study these changes were investigated in healthy controls and AHLH patients.

Results: A91V transition was observed in 7 of the 159 (4.4%) controls. Among the 44 AHLH patients, 5 (11.3%) were heterozygous and the difference in the frequency of A91V transition, although striking (odds ratio: 2.8), was not statistically significant (p=0.09). All A91V-positive patients had infection. TNF-α-1031 T>C polymorphism was examined in 164 healthy controls and 40 AHLH patients, and the CC risk-elevating genotype was noted in 7 (4.3%) of the controls and 1 (2.5%) of the AHLH patients. The frequency of C and T alleles was 22.5% (n=18) and 77.5% (n=62) among the AHLH patients, and 22% (n=72) and 78% (n=259) among the controls, respectively. There wasn't a statistically significant difference between the groups in terms of allele frequencies (p>0.05).

Conclusion: The present results indicate that compared to controls, A91V mutation was 2.8-fold more prevalent (according to the odds ratio) in the AHLH patients. A91V mutation is not uncommon in the general population and increases the risk of AHLH in patients with an underlying condition, especially those with an underlying infection.
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http://dx.doi.org/10.5152/tjh.2011.28DOI Listing
June 2011

Prenatal diagnosis of hemoglobinopathies in Hacettepe University, Turkey.

Pediatr Hematol Oncol 2011 Feb 23;28(1):51-5. Epub 2010 Sep 23.

Division of Maternal Fetal Medicine and Perinatology, Department of Obstetrics and Gynecology, Hacettepe University, Faculty of Medicine, Ankara, Turkey.

Between 1983 and 2008, prenatal diagnostic procedures for identifying hemoglobinopathies were performed in 947 at-risk fetuses. Seventy-six percent of the fetuses were at risk for β-thalassemia major and 16% for sickle cell anemia; only a small percentage (7%) were at risk for compound heterozygosity of β-thalassemia and an abnormal hemoglobin of the β chain. The results of the study showed that β gene mutations in hemoglobinopathies have a very broad spectrum. Seven hundred and thirty of the 947 fetuses examined using the DNA technique showed 88 different combinations of 27 different mutations. Although the number of fetuses evaluated was far below the desired target, the termination of 261 affected fetuses provided both psychological and economic relief for the parents and was economically beneficial for the country in the long term.
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http://dx.doi.org/10.3109/08880018.2010.507690DOI Listing
February 2011

Infectious mononucleosis in Turkish children.

Turk J Pediatr 2010 May-Jun;52(3):245-54

Unit of Infectious Diseases, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

The aim of this study was to analyze the demographic, clinical and laboratory characteristics and prognoses of children diagnosed with infectious mononucleosis (IM). The demographic features, referral complaints, clinical and laboratory findings, follow-up, and prognoses of 44 patients diagnosed with IM between January 2000 and June 2006 at the Infectious Diseases Department of Hacettepe University Ihsan Doğramaci Children's Hospital were analyzed retrospectively. The children suspected of IM based on clinical findings and whose diagnoses were proven by serological tests were enrolled in the study. In addition, the patients were divided into four groups -namely, age 0-4, age 5-8, age 9-12 and age 13-16, and the differences among groups were investigated in terms of their clinical and laboratory findings. The patients were aged between 3 months and 16 years. The median age was 4, and 56.8% of patients were below age 5. The male/female ratio was 1.6. No statistically significant variation was observed in the seasonal distribution of patients (p = 0.131). The most common referral complaints were swollen cervical lymph nodes or swollen neck (68.1%), followed by fever (43.1%) and sore throat (25%). Lymphadenopathy (79.5%), tonsillopharyngitis (72.7%), splenomegaly (34%), and hepatomegaly (25%) were the most common physical examination findings. Leukocyte count was normal in 68.3% of the cases. Leukocytosis was detected in 29.5% of the patients, and leukopenia in 2.2%. Lymphocytosis was detected in 44.7% of patients. Downey cell was detected in the peripheral blood smear of 23.6% of patients, and thrombocytopenia in 11.3%. Elevated alanine aminotransferase and aspartate aminotransferase levels were detected in 61.9% and 90.4% of patients who were investigated for these parameters, respectively. The clinical, hematological and biochemical findings of patients did not vary significantly among age groups (p > 0.05). Only one complication (hemophagocytic syndrome) was observed in one patient.
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September 2010

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) for the treatment of children with poor-prognosis acute leukemia: the Hacettepe experience.

Pediatr Hematol Oncol 2010 Oct;27(7):517-28

Pediatric Hematology Unit, Ihsan Dogramacı Children's Hospital, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Fludarabine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and idarubicin (FLAG-IDA) regimen has been proven to be a potentially useful chemotherapy regimen for relapsed or poor-prognosis childhood leukemia. The aim of the study was to evaluate complete remission (CR) rate, toxicity, and overall survival of children with poor-prognosis acute leukemia who received the FLAG-IDA regimen. Furthermore, the authors investigated the children who achieved CR following FLAG-IDA treatment regarding their eligibility for allogeneic hematopoietic stem cell transplantation (HSCT). Between January 2002 and April 2007, 25 children with poor-prognosis acute leukemia were treated with FLAG-IDA regimen in our center. Of the 25 children (16 AML, 9 ALL) with poor-prognosis acute leukemia, 7 (28.0%) received 1 cycle, 17 (68.0%) received 2 cycles, and 1 (4%) received 3 cycles of FLAG or FLAG-IDA regimen. After 44 cycles of FLAG-IDA or FLAG regimen, 10/25 (40%) children were nonresponders, 15/25 (60.0%) showed CR. Five (20%) of these patients in CR who underwent allogeneic HSCT are still in remission. The remaining 20 (80.0%) children were lost due to infection or relapse of the primary diseases. The overall survival of patients who are still alive and underwent allogeneic HSCT (mean: 40.6 ± 4.7, median: 40, range: 34-46 months) was longer than that of patients (mean: 5.5 ± 4.3, median: 4, range: 1-15 months) who did not undergo allogeneic HSCT. The CR rate was quite high in the present study using the FLAG-IDA regimen, and the authors believe this regimen is a possible option prior to allogeneic HSCT in children with poor-prognosis acute leukemia.
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http://dx.doi.org/10.3109/08880018.2010.493578DOI Listing
October 2010

An unusual presentation of pediatric acute lymphoblastic leukemia with parotid gland involvement and dactylitis.

Turk J Haematol 2010 Jun;27(2):117-9

Hacettepe University, Division of Pediatric Hematology 06100 Ankara, Türkiye Phone: + 90 312 305 11 70 E-mail:

Mumps infection during the course of childhood acute lymphoblastic leukemia (ALL) treatment has been reported to have a mild course and this was related to the intrinsic low cytopathological effect of the virus, contrasting with the severe course of measles and Varicella zoster virus infections in immunocompromised patients. Herein, we present a three-year-old girl, who was previously vaccinated against mumps infection, admitted with bilateral parotid swelling, dactylitis and serum immunoglobulin M positivity for mumps infection and diagnosed to have ALL with bilateral persistent parotid involvement, inconsistent with mumps infection. Acute leukemia should be suspected during the atypical course of any disease during childhood. Besides, mumps infection at presentation of ALL, as similar to infection emerging during the period of the leukemia treatment, has a mild course.
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http://dx.doi.org/10.5152/tjh.2010.10DOI Listing
June 2010

Measles, mumps, and rubella antibody status and response to immunization in children after therapy for acute lymphoblastic leukemia.

Pediatr Hematol Oncol 2010 Aug;27(5):333-43

Hematology Unit Hacettepe University Ihsan Doğramaci Children's Hospital, Hematology Unit, Ankara, Turkey.

Seventy-seven patients with acute lymphoblastic leukemia (ALL) who were in complete remission and whose therapies had been stopped for at least 6 months before enrollment in this study were retrospectively analyzed regarding their antibody status for measles, mumps, and rubella, with the aim to demonstrate the seropositivity rate after treatment in the authors' group. Each patient's serum samples were analyzed by enzyme-linked immunosorbent assay (ELISA) method to determine the antibody titers before and after immunization. Measles serology was available in 77 children; 45 (58%) were seronegative. Initial ages of measle-seronegative patients were statistically lower than those of seropositive cases (median 3.29 versus 4.91 years, respectively). Mumps serology was available in 76 children; 36 (47%) were seronegative. Mumps-seropositive cases tended to have more frequent previous history of infection than seronegative cases (55.0% versus 28.6%, respectively, P = .05). Rubella serology was available in 76 children, and 20 (26.3%) were seronegative. It was determined that initial ages of rubella-seronegative patients were statistically lower than those of seropositive cases (median 3.03 versus 4.32 years, respectively). The authors concluded based on the results of their study that at a median of 3.31 years after completion of chemotherapy for ALL, the majority of cases had antibody levels lower than protective values for measles (58.4%); however, these values were 47.3% for mumps and 26.3% for rubella. Seroconversion rates after measles (55%) and mumps vaccination (57.1%) were still low. However, in the available cases, relatively adequate response to rubella vaccination (92.3%) was observed.
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http://dx.doi.org/10.3109/08880011003767720DOI Listing
August 2010

Plasminogen activator inhibitor I 4G/5G polymorphism in neonatal respiratory distress syndrome.

Clin Appl Thromb Hemost 2011 Aug 11;17(4):352-7. Epub 2010 May 11.

Department of Pediatrics, Neonatology Unit, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Fibrin monomers inhibit surfactant function. 4G/5G insertion/deletion polymorphism plays an important role in the regulation of plasminogen activator inhibitor 1 (PAI-1) gene expression. To examine the genotype distribution of PAI-1 polymorphism in 60 infants with respiratory distress syndrome (RDS) and 53 controls, an allele-specific polymerase chain reaction (PCR) was used. The proportion of 4G/4G, 4G/5G, and 5G/5G genotypes did not differ statistically between the RDS and control groups (P > .05). Having PAI-1 4G/4G genotype polymorphism appears to increase the risk of RDS (odds ratio [OR] =1.5; 95% confidence interval [CI], 0.5-4.3), although it was not statistically significant. No relation was found between the PAI-1 4G/5G polymorphisms and RDS, but there was an increased risk associated with the 4G variant of the PAI-1 gene. We believe that our findings of increased 4G allele of the PAI-1 gene in infants with RDS would also help to clarify the pathogenesis of RDS.
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http://dx.doi.org/10.1177/1076029610369796DOI Listing
August 2011

Assessment of clinical and laboratory presentations of familial hemophagocytic lymphohistiocytosis patients with homozygous W374X mutation.

Leuk Res 2010 Aug 1;34(8):1012-7. Epub 2010 Mar 1.

Hacettepe University, Department of Pediatrics, Section of Pediatric Hematology, Ankara, Turkey.

Homozygous W374X mutation was identified in unrelated 13 patients (6M/7F) from consanguineous families, 62% of which had history of deceased sibling. Haplotype analysis provided evidence for the probable existence of a founder effect. Age at disease onset ranged from 1 day to 5.5 months (median 2 months). Hepatic dysfunction was observed in 69%, ascite 62%, hypertriglyceridemia 77%, each hyperferritinemia and hypofibrinogenemia 85%, CNS involvement 46% of patients while birth weights were in normal range. Those with very high ferritin (>20,000ng/ml) had extremely low fibrinogen levels. Two-thirds of patients receiving HLH protocol died within 20 days of therapy.
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http://dx.doi.org/10.1016/j.leukres.2010.02.002DOI Listing
August 2010

Hydrops fetalis associated with chorioangioma and thrombosis of umbilical vein.

Turk J Pediatr 2009 Sep-Oct;51(5):515-8

Unit of Neonatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Placental chorioangioma and thrombosis of an umbilical vein varix are rare etiologic factors of non-immune hydrops fetalis. Herein, we report a patient who had hydrops fetalis associated with placental chorioangioma and thrombosis of an umbilical vein varix. This is the first report of coexistence of non-immune hydrops fetalis with placental chorioangioma and thrombosis of an umbilical vein varix.
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February 2010

Mild clinical phenotype and subtle radiographic findings in an infant with cartilage-hair hypoplasia.

Turk J Pediatr 2009 Sep-Oct;51(5):493-6

Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Cartilage-hair hypoplasia (CHH) is one of the well-known immuno-osseous dysplasias (IOD), which are a combination of skeletal dysplasia and immunodeficiency. It is characterized by disproportionate short stature, fine sparse hair, ligamentous laxity, hematological abnormalities with anemia, a predisposition to malignant tumors, and recurrent infections usually due to cellular and/or humoral immunodeficiency. However, there is a significant overlap of clinical findings among the other IODS such as Schimke's IOD. Here, we present a case of CHH with mild skeletal changes and immunological findings associated with recurrent otitis media, neutropenia, and lymphopenia. With this report, we once more emphasize the difficulty in assessing young individuals with CHH presenting with mild ectodermal findings and subtle radiographic changes.
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February 2010

Purpura fulminans as the presenting manifestation in a patient with juvenile SLE.

Turk J Pediatr 2009 Jul-Aug;51(4):378-80

Units of Pediatric Rheumatology and Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

We present a 12-year-old girl with systemic lupus erythematosus and associated antiphospholipid syndrome who developed an unusual manifestation of purpura fulminans in an accelerated fashion. The patient improved after prompt treatment with anticoagulants, aggressive immunosuppressive drugs and plasmapheresis. This is the first pediatric case of purpura fulminans due to secondary antiphospholipid syndrome of systemic lupus erythematosus. We suggest that SLE patients with lupus anticoagulant should be followed closely for similar complications.
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January 2010

Malignancy-associated hemophagocytic lymphohistiocytosis in pediatric cases: a multicenter study from Turkey.

Turk J Pediatr 2009 May-Jun;51(3):207-13

Department of Pediatric Hematology-Oncology, Istanbul University Cerrahpaşa Faculty of Medicine, Istanbul, Turkey.

This study evaluates the clinical and laboratory data of children with secondary hemophagocytic lymphohistiocytosis (sHLH) related to malignancy. Charts of patients who met the diagnostic criteria for sHLH associated with malignancy between January 2000-2006 at six different hospitals in Turkey were reviewed retrospectively. The diagnosis of HLH had been established by bone marrow aspiration in 27 patients, cerebrospinal fluid and bone marrow aspiration in one patient and lung-liver biopsy in another. Twenty-nine children were diagnosed as having sHLH related to malignancy. Twenty cases (18 ALL and 2 AML) with acute leukemia (10 girls/10 boys, median age: 8 years [3-14 years]) were found to have sHLH. Five patients with acute leukemia had HLH at the time of diagnosis (Group 1a), and 15 patients with acute leukemia were diagnosed as having sHLH during therapy (Group 1b), namely reactive sHLH associated with the chemotherapy. Nine patients, including two cases each of rhabdomyosarcoma, neuroblastoma, Hodgkin disease, and non-Hodgkin lymphoma (NHL) and one case with Langerhans cell histiocytosis, were diagnosed as having concomitant hemophagocytosis at the initial evaluation of the tumor (Group 2). Fever, anemia, and hypertriglyceridemia were present in all sHLH cases of all three groups. Hepatomegaly was detected in 60.0%, 73.3%, and 88.8% of the three groups, respectively. Splenomegaly was more frequent in patients of Groups 1a (60.0%) and 2 (88.8%) than in those of Group 1b, the reactive ones (13.3%). Hypofibrinogenemia was detected in all patients of Group 1a and Group 2. Low level of fibrinogen was present in 91.6% of patients in Group 1b. All patients in Group 1b (100%) had neutropenia and thrombocytopenia. Neutropenia was found at rates of 60.0% and 55.5% in Group 1a and Group 2, respectively. Thrombocytopenia was detected in 80.0% of patients in Group 1a and 77.7% in Group 2. The overall mortality rate was 34.4% (10 cases) in our series of 29 children with sHLH; 50% of deaths were directly attributable to HLH. Pediatric malignancy-associated HLH patients have been commonly described as case presentations or in a review of the literature. We believe that our cohort, compiling 29 children regarding the association between malignancy and HLH, will be useful for pediatricians who are interested in this still mysterious topic.
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October 2009

Hemophagocytosis associated with leukemia: a striking association with juvenile myelomonocytic leukemia.

Ann Hematol 2010 Apr 2;89(4):359-64. Epub 2009 Oct 2.

Department of Pediatrics, Division of Pediatric Hematology, Hacettepe University, Faculty of Medicine, 06100 Sihhiye, Ankara, Turkey.

The aim of this study was to describe the characteristics and outcome in a group of pediatric patients with hematological malignancies who developed hemophagocytosis at diagnosis or during the disease course. Eight patients with hematological malignancy and associated hemophagocytosis were included. The initial diagnosis was juvenile myelomonocytic leukemia (JMML) in five, nonlymphoblastic leukemia (ANLL) in two, and T-cell lymphoma associated with myeloproliferative syndrome in one patient. Hemophagocytosis was concomitantly present at the time of diagnosis of the primary disease in four of the five patients with JMML and in the two patients with ANLL. Three had abnormalities related to chromosome 8 [(trisomy 8, monosomy 8, and t (8;13) (p11; p12)], and one had inversion 16. Multiple chromosomal losses were present in one patient, including both chromosomes 8 and 16. Bone marrow karyotyping revealed 46, XX; 47, XXX mosaicism in one patient. Two patients had PTPN11 mutation and one patient k-RAS mutation. The patients with JMML and neurofibromatosis (n = 2), the patient with lymphoma and t (8;13) positive AML, and a fourth patient with PTPN11 mutation did not remit and had unfavorable outcomes.
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http://dx.doi.org/10.1007/s00277-009-0837-0DOI Listing
April 2010

Hypertrichosis: the possible side effect of cyclosporin in an infant with hemophagocytic lymphohistiocytosis receiving HLH-2004 chemotherapy protocol.

Turk J Haematol 2009 Sep;26(3):154-6

Department of Pediatric, Hacettepe University Medical School, Ankara, Turkey, Phone: +90 312 3051167 E-mail:

Hemophagocytic lymphohistiocytosis is a life-threatening condition of severe hyperinflammation that results from an uncontrolled proliferation of activated lymphocytes and histiocytes secreting high amounts of inflammatory cytokines. The immediate treatment strategies include immune suppressive therapy such as corticosteriod, etaposide and cyclosporin A. Herein, we present a 13- month-old infant, who developed severe hypertrichosis after the administration of HLH-2004 treatment protocol and discuss the various hypotheses regarding the causal relationship between cyclosporine A and hypertrichosis, emphasizing the importance of patient follow up.
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September 2009

Serum Erythropoietin Levels in Pediatric Hematologic Disorders and Impact of Recombinant Human Erythropoietin Use.

Turk J Haematol 2009 Jun;26(2):72-6

Hacettepe University, Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, 06100, Sıhhiye, Ankara, Turkey, Phone: +90 312 305 11 72 Fax: +90 312 311 23 98 E-mail:

Objective: In anemic patients, the correlation between serum erythropoietin (sEpo) level and the severity of anemia has been reported previously. However, in different anemia groups, different sEpo levels are measured in patients with similar hemoglobin levels and the etiology of this situation could not be explained.

Methods: We evaluated hemoglobin and sEpo levels in 31 iron deficiency anemia, 26 Fanconi anemia (FA), 21 thallasemia intermedia (TI), 15 acute lymphoblastic leukemia (ALL) patients at presentation and 12 healthy controls.

Results: In all disease groups, an inverse linear correlation was shown between hemoglobin and logarhytmic sEpo level. The covariance analyses according to corrected hemoglobin levels exhibited the highest sEpo level in FA, followed by ALL, TI and iron deficiency anemia, sequentialy.

Conclusion: There was no statisticaly significant difference of sEpo levels in FA patients in terms of androgen treatment and this finding supports that androgen affects erythropoisis directly, and has no effect on erythropoietin. The results indicate that there is no erythropoietin deficiency in the anemia of these patients and the admnistration of exogenous erythropoietin offers no clinical benefit.
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June 2009

From the editor.

Authors:
Aytemiz Gürgey

Turk J Haematol 2009 Jun;26(2):46

Department of Pedaitric Hematology, Hacettepe University Faculty of Medicine, Ankara, Turkey, Phone: +90 312 305 41 17 E-mail:

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June 2009

Parvovirus B19-induced persistent pure red cell aplasia in a child with T-cell immunodeficiency.

Pediatr Hematol Oncol 2009 Mar;26(2):63-8

Hacettepe University, Pediatric Hematology Unit, 06100-Sihhiye, Ankara, Turkey.

Persistent pure red cell aplasia can be a manifestation of parvovirus B19 infection in immunocompromised hosts. Failure of the humoral immune response to clear parvovirus B19 in such patients results in persistent pure red cell aplasia. The authors describe a child who had T-cell immunodeficiency and persistent pure red cell aplasia due to parvovirus B19 infection. Interestingly, they detected human parvovirus B19 genome by polymerase chain reaction (PCR) not in the peripheral blood, but in the bone marrow specimen of the patient. In their patient, T-cell immunodeficiency may have caused impaired B-cell activation and failure of effective humoral immune response to neutralize the virus. Additionally, before the diagnosis of pure red cell aplasia, IVIG treatment given at a dosage of 400 mg/kg/day with 3-week intervals may result in sufficient neutralization of peripheral blood parvovirus B19, whereas it may not be sufficient for the neutralization of parvovirus B19 genome in bone marrow. Thus, peripheral blood parvovirus B19 serology (IgM and IgG) and PCR were negative, whereas bone marrow aspiration sample was positive for parvovirus B19 PCR in this patient. Reticulocytopenia and severe anemia may warn the physicians of parvovirus B19 infection, especially in immunocompromised children. Diagnosis may require demonstration of absence of late erythroid precursors in the bone marrow as well as serologic testing and detection of parvovirus B19 genome by PCR in the serum and/or bone marrow samples of the patient.
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http://dx.doi.org/10.1080/08880010902754735DOI Listing
March 2009

Transient depletion of innate immunity in varicella infections in otherwise healthy children.

Turk J Haematol 2009 Mar;26(1):12-6

Hacettepe University, Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, 06100 Sihhiye, Ankara,Turkey, Phone: +90 312 305 11 70 Fax: +90 312 311 23 98 E-mail:

Objective: Varicella is a common childhood infection and has a number of complications in the unvaccinated population. Perforin, found in natural killer cells, is important for the killing of virally infected cells. For this reason, the aim of this study was to determine natural killer cell count and activity, perforin expression, and Fas and soluble Fas ligand (sFas-L) levels in immunocompetent children with varicella infection and define any possible relations between the levels and varicella complications.

Methods: Forty children were analyzed at diagnosis and on the 15th day of varicella infection. There was a significant difference in hemoglobin levels and leukocyte and platelet counts between days 0 and 15.

Results: Thirteen (32%) patients were found to be lymphopenic. Natural killer cell count and activity were significantly higher on day 15 when compared to values at diagnosis. The Fas-mediated apoptotic pathway was found to be active in acute varicella infection because Fas and sFas-L levels at diagnosis were higher than values on day 15.

Conclusion: These findings suggest that the Fas and Fas-L apoptotic pathway is active during the acute phase of the viral infection and that it becomes inactive by day 15, paralleling the hematologic recovery.
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March 2009

Two new cases with Pearson syndrome and review of Hacettepe experience.

Turk J Pediatr 2008 Nov-Dec;50(6):572-6

Unit of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Pearson syndrome (PS) is a mitochondrial disease and clinical presentation is rather varied. These patients are often subjected to extensive biochemical and clinical work-up for diagnosis. We report two new cases and review our experience with PS in Hacettepe University. The first case had large deletion of mitochondrial DNA (mtDNA) and presented with severe metabolic acidosis and anemia associated with hemophagocytosis in bone marrow. He also had liver involvement and tubulopathy. The second case, who had the 4997 bp common deletion, presented with anemia at 8 weeks of age followed by an uneventful 4 years. She developed very severe acidosis and renal Fanconi syndrome at the age of 4.5 years. Our cases revealed once more the clinical diversity of the disease and no correlation between the size and site of mtDNA deletion and clinical presentation. We encourage physicians to look for PS in children with early sideroblastic anemia and multiple organ system involvement.
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March 2009