Hannah Tamary

Schneider Children's Medical Center of Israel, Petah Tikva, Central District, Israel

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Publications (109)375.93 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Because Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) patients have microthrombocytopenia, hemorrhage is a major problem. We asked whether eltrombopag, a thrombopoietic agent, would increase platelet counts, improve platelet activation, and/or reduce bleeding in WAS/XLT patients. In 9 WAS/XLT patients and 8 age-matched healthy controls, platelet activation was assessed by whole blood flow cytometry. Agonist-induced platelet surface activated GPIIb-IIIa and P-selectin in WAS/XLT patients were proportional to platelet size and therefore decreased compared to controls. In contrast, annexin V binding showed no differences between WAS/XLT and controls. Eltrombopag treatment resulted in an increased platelet count in 5 out of 8 patients. Among responders to eltrombopag, immature platelet fraction in 3 WAS/XLT patients was significantly less increased compared with 7 pediatric chronic immune thrombocytopenia (ITP) patients. Platelet activation did not improve in 3 WAS/XLT patients whose platelet count improved on eltrombopag. 1) The reduced platelet activation observed in WAS/XLT is primarily due to the microthrombocytopenia. 2) Although the eltrombopag-induced increase in platelet production in WAS/XLT is less than in ITP, eltrombopag has beneficial effects on platelet count, but not platelet activation, in the majority of WAS/XLT patients. This trial was registered at www.clinicaltrials.gov as #NCT00909363. Copyright © 2015 American Society of Hematology.
    Blood 07/2015; 126(11). DOI:10.1182/blood-2014-09-602573 · 10.45 Impact Factor
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    ABSTRACT: Dyskeratosis congenita (DC) and related diseases are a heterogeneous group of disorders characterized by impaired telomere maintenance, known collectively as the telomeropathies. Disease causing variants have been identified in ten telomere-related genes including the reverse transcriptase (TERT) and the RNA component (TERC) of the telomerase complex. Variants in TERC and TERT can impede telomere elongation causing stem cells to enter premature replicative senescence and/or apoptosis as telomeres become critically short. This explains the major impact of the disease on highly proliferative tissues such as the bone marrow and skin. However telomerase variants are not always fully penetrant and in some families disease causing variants are seen in asymptomatic family members. As a result determining the pathogenic status of newly identified variants in TERC or TERT can be quite challenging. Over a three year period we have identified 26 telomerase variants (16 of which are novel) in 23 families. Additional investigations (including family segregation and functional studies) enabled these to be categorized into three groups: (a) disease causing (n=15), (b) uncertain status (n=6) and (c) bystanders (n=5). Remarkably this process has also enabled us to identify families with novel mechanisms of inheriting human telomeropathies. These include triallelic mutations, involving two different telomerase genes, and an epigenetic-like inheritance of short telomeres in the absence of a telomerase mutation. This study therefore highlights that telomerase variants have highly variable functional and clinical manifestations and require thorough investigation to assess their pathogenic contribution. Copyright © 2015 American Society of Hematology.
    Blood 05/2015; 126(2). DOI:10.1182/blood-2015-03-633388 · 10.45 Impact Factor

  • 03/2015; 2. DOI:10.13070/ev.en.2.1361
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    ABSTRACT: Background The use of central venous catheters (CVCs) has greatly improved the quality of care in children receiving chemotherapy, yet these catheters may cause serious infectious complications. The aim of this prospective registry study was to assess the host and CVC-related risk factors for blood stream infections (BSIs).ProcedurePatients undergoing CVC insertion for chemotherapy were followed prospectively for CVC complications. At the time of enrollment demographic-, clinical- and CVC-related data were collected. Survival and Cox-regression analysis were performed.ResultsA total of 423 CVCs were inserted into 262 patients for a total of 76,540 catheter-days. The incidence of BSIs was 1.95 per 1,000 patient-days (95% CI 1.66–2.29). Myeloid leukemia and younger age were associated with higher risk for BSI. At least one BSI occurred in 187 CVCs with an incidence of 2.84 per 1,000 catheter-days (95% CI 2.47–3.24). Externalized CVCs, that is, tunneled externalized catheters and peripheral inserted central catheters, were associated with higher risk for BSI in the group of diseases with relatively lower rate of infection. However, in diseases with high rate of infection no such association was found. The type of BSI was associated with the diagnosis and the CVC type. CVC occlusion was associated with higher risk for recurrent BSI and for coagulase negative staph BSI.Conclusions Both patient and CVC-related factors are associated with higher risk of BSI in children receiving chemotherapy. The results of this study could be used in developing studies aiming to reduce the rate of BSIs in children with cancer. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 10/2014; 62(3). DOI:10.1002/pbc.25281 · 2.39 Impact Factor
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    ABSTRACT: The molecular basis of α-thalassemia (α-thal) is complex. The use of multiplex ligation-dependent probe amplification (MLPA) has offered the possibility of identifying more gene deletions causing α-thal. Our objective was to determine the molecular basis of two patients with Hb H (β4) disease. By using MLPA in combination with comparative genomic hybridization (CGH) we identified two novel α-globin gene cluster deletions: a 30 kb deletion (patient 1) we refer to as – –JAL and a large 216 kb deletion (patient 2) we refer to as – –LOD. Patient 1 was a compound heterozygote for – –JAL and –α3.7 (rightward deletion). Twelve family members of patient 1 carrying the – –JAL deletion were available for evaluation: five with – –JAL/–α3.7, four with – –JAL/αHph Iα and three with – –JAL/αα. Their clinical picture of compound heterozygosity was compatible with moderate Hb H disease. In patient 2 (– –LOD/–α3.7), no additional symptoms were present despite the heterozygous deletion of seven known genes, three non coding RNAs (ncRNAs), four unknown genes and two pseudo genes. Further analysis of more patients with α-thal deletions will have implications for genetic counseling and appropriate therapy.
    Hemoglobin 09/2014; 38(5). DOI:10.3109/03630269.2014.954668 · 0.79 Impact Factor
  • Joanne Yacobovich · Hannah Tamary ·
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    ABSTRACT: The increased longevity of patients with thalassemia and sickle cell disease (SCD) introduces new clinical challenges due to the accumulation of disease-related morbidity, psychosocial issues and health care adjustments. Patients with thalassemia major now live into adulthood without suffering heart failure but must confront delayed puberty, impaired fertility and progressive bone disease. The increased survival in SCD brings to the front previously unrecognized complications including pulmonary hypertension, silent cerebral infarcts and also reproductive dysfunction. Adolescents and young adults (AYAs) have age-related psychosocial needs in their transition from the pediatric health care environment to the adult system. In this review we present the uniquely age-related medical issues facing the AYA thalassemia and SCD cohort in their transition into adulthood. © 2014 S. Karger AG, Basel.
    Acta Haematologica 09/2014; 132(3-4):340-7. DOI:10.1159/000360235 · 1.12 Impact Factor
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    ABSTRACT: Background The relative frequency of mutated genes among patients with severe congenital neutropenia (SCN) may differ between various ethnic groups. To date, few population-based genetic studies have been reported. This study describes the genetic analysis of 32 Israeli patients with SCN.ProceduresClinical data were retrieved from the prospective Israeli Inherited Bone Marrow Failure Registry. Recruitment included living and deceased patients who were diagnosed between 1982 and 2012, for whom molecular diagnosis was performed. ELANE, HAX1 and G6PC3 genes were sequenced in all patients, and GFI-1 and WAS genes were sequenced if other genes were wildtype.ResultsEleven patients (34%) had heterozygous mutations in ELANE (10 kindreds), eight (25%) had homozygous mutations in G6PC3 (5 kindreds) and 13 (41%) had no detected mutations. No patients had mutations in HAX1 or WAS. Four of the eight patients with G6PC3 mutations had congenital anomalies. The probability of survival for all patients was 50% at age of 18. Deaths were mainly due to sepsis (5 patients, 4/5 not responding to G-CSF, none with G6PC3 mutation). Two patients developed acute myelogenous leukemia (AML) and one myelodysplastic syndrome (MDS), none with G6PC3 mutation.Conclusions We found a unique pattern of SCN mutations in Israel with homozygous G6PC3 mutations in eight (25%) patients, the highest frequency described so far. HAX1 mutations, reported mainly in Sweden and Iran, were absent. Patients with G6PC3 mutations had congenital anomalies, appeared to have a better response to G-CSF, and so far have not developed AML or MDS. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 09/2014; 62(1). DOI:10.1002/pbc.25251 · 2.39 Impact Factor
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    ABSTRACT: Long-term Granulocyte-Colony Stimulating Factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on the use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European Branch of the Severe Chronic Neutropenia International Registry since 1994. A total of 38 pregnancies in 21 women with chronic neutropenia (16 pregnancies in 10 women with congenital, 10 in six women with cyclic, 12 in five women with idiopathic neutropenia) were reported. Granulocyte-Colony Stimulating Factor was administered throughout pregnancy in 16 women and for at least one trimester in further five women. No major differences were seen between treated and untreated women with respect to pregnancy outcome, newborn complications and infections. In addition, we evaluated the genetic transmission of known or suspected genetic defects in 16 mothers having 22 newborns as well as in eight men fathering 15 children. As a proof of inheritance, neutropenia was passed on to the newborn in 58 percent from female and in 62 percent from male patients revealing ELANE mutations, but also to some newborns from parents with unknown gene mutation. Based on our results, Granulocyte-Colony Stimulating Factor therapy has been shown to be safe for mothers throughout pregnancies and newborns without any signs of teratogenicity. With an increasing number of adult patients, genetic counseling prior to conception and supportive care of mothers during pregnancy is crucial. The acceptance of having affected children may reflect the high quality of life due to this treatment.
    Haematologica 07/2014; 99(8). DOI:10.3324/haematol.2013.099101 · 5.81 Impact Factor
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    ABSTRACT: We describe the clinical and laboratory features of a family of Arab ancestry and consanguinity. Five affected individuals were diagnosed in two sibships. All affected members have small platelets, severe to moderate thrombocytopenia of neonatal onset, increased bleeding tendency and bleeding complications such as: life-threatening massive hemoperitoneum due to corpus luteum rupture during ovulation and severe mucosal bleeding. The familial involvement and early onset of the disease support the presence of a congenital genetic disorder with an autosomal recessive inheritance pattern. This does not fit the clinical spectrum of any of the currently known thrombocytopenia disorders. Pediatr Blood Cancer 2013;9999:XX-XX. © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 10/2013; 60(10). DOI:10.1002/pbc.24581 · 2.39 Impact Factor
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    ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is caused by an excessive activation of nonmalignant macrophages. Renal lesions have been described in association with, but always after, HLH diagnosis. We describe a previously healthy 26-month-old girl who presented originally with steroid-responsive nephrotic syndrome (NS), but after 4 months, on the first NS relapse, experienced numerous complications (many of them reported to accompany NS as single events). Clinical and laboratory signs of HLH evolved with time and led to deterioration of her condition and death, within 5 months of her original presentation. To our knowledge, this is the first report of NS antedating the presentation of HLH.
    Pediatric Nephrology 08/2013; 28(12). DOI:10.1007/s00467-013-2583-8 · 2.86 Impact Factor
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    Achille Iolascon · Hermann Heimpel · Anders Wahlin · Hannah Tamary ·
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    ABSTRACT: The congenital dyserythropoietic anemias (CDAs) are hereditary disorders characterized by distinct morphological abnormalities of marrow erythroblasts. The unveiling of the genes mutated in the major CDA subgroups (I-CDAN1, II-SEC23B) has now been completed with the recent identification of the CDA III gene (KIF23). KIF23 encodes mitotic kinesin-like protein 1 which plays a critical role in cytokinesis, while the cellular role of the proteins encoded by CDAN1 and SEC23B is still unknown. CDA variants with mutations in erythroid transcription factors genes (KLF1, GATA-1) have been recently identified. Molecular diagnosis of CDA is now possible in most patients.
    Blood 08/2013; 122(13). DOI:10.1182/blood-2013-05-468223 · 10.45 Impact Factor
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    ABSTRACT: To evaluate the predictive value of clinical features at diagnosis of immune thrombocytopenia (ITP) for resolution of disease. Hospital records of 472 consecutive children (<18 years old) with ITP cared for at 2 participating centers were reviewed retrospectively and data related to the initial presentation were recorded. Logistic regression analysis was used for calculating prediction of resolution at 3, 6, and 12 months from diagnosis. The most significant predictors for resolution of ITP at 3, 6, and 12 months were age at onset <10 years and abrupt onset (history of <2 weeks of bleeding). We designed a prediction rule for ITP chronicity based on these criteria. The rate of developing chronic ITP for low, intermediate, and high risk children at diagnosis of ITP was 11%, 39%, and 63%, respectively. Recovery rate at 3 months for low, intermediate, and high risk children was 72%, 43% and 30%, respectively. We present a simple rule to predict recovery from ITP at 3, 6, and 12 months from diagnosis. For prediction of resolution at 3 months, our rule was in agreement with the more complex, previously described Nordic score. Prediction of resolution of ITP may enable practitioners to better inform children and parents at the time of diagnosis, resulting in reduced anxiety and improved quality of life.
    The Journal of pediatrics 07/2013; 163(5). DOI:10.1016/j.jpeds.2013.06.018 · 3.79 Impact Factor
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    Joanne Yacobovich · Shoshana Revel-Vilk · Hannah Tamary ·
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    ABSTRACT: Although the majority of children with immune thrombocytopenia (ITP) have a short duration of the disease, the very rare but significant complications of the disease often cause fear and anxiety among families of children with ITP. Added to the reduced quality of life (QoL) of those children are restrictions imposed on daily activities to avoid trauma. Treatment decisions in chronic ITP and especially regarding splenectomy are hampered by the inability to predict when recovery will take place. Identification of predictors of recovery would be beneficial for improving treatment decisions and QoL of both children and families. This literature review focuses on clinical parameters and emerging genetic biomarkers for prediction of duration of childhood ITP. Higher recovery rates were found among infants with newly diagnosed ITP. In contrast onset of the disease at adolescence was associated with worse recovery rates. Six clinical features were found to be associated with short duration of disease; the most prominent ones were abrupt onset of bleeding symptoms (<2 weeks) and age at onset≤10 years. Two genetic biomarkers have been suggested as predictors of chronic disease: overexpression of vanin-1 (VNN-1), an oxidative stress sensor, and the Q63R missense variant of the gene encoding the cannabinoid receptor type 2. To be clinically useful each of those predictors requires further validation in larger studies. Genetic biomarkers will potentially offer direct and early prognosis estimation.
    Seminars in Hematology 05/2013; 50 Suppl 1:S71-4. DOI:10.1053/j.seminhematol.2013.03.013 · 3.27 Impact Factor
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    ABSTRACT: Thrombocytosis is a common finding and is a frequent cause of referral for further investigation. The MPL Baltimore (Lys39Asn) mutation has been reported as a cause of thrombocytosis in 7% of African Americans. We describe an 11-month-old Ethiopian Jewish boy referred for evaluation of thrombocytosis who was found to be homozygous for MPL Baltimore. So far, there is no indication whether patients with thrombocytosis who have this mutation, particularly homozygotes, are at increased risk of thrombotic or hemorrhagic complications. Nevertheless, this entity should be considered in the differential diagnosis of every patient with thrombocytosis, particularly those of African origin.
    Journal of Pediatric Hematology/Oncology 04/2013; 35(3):e112-4. DOI:10.1097/MPH.0b013e318286d54c · 0.90 Impact Factor
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    ABSTRACT: : We constructed an animal model to examine the possibility that erythrophagocytosis may contribute to decreased hemoglobin (Hgb) levels in acute infection in mice. : BALB/c mice weighing 20 to 25 g were injected (intraperitoneally) with lipopolysaccharide (LPS) (Escherichia coli serotype) of some concentrations. Control mice were injected intraperitoneally with saline (0.5 mL). Two and 4 hours after LPS administration, mice were bled (0.25 mL) for complete blood count measures and tumor necrosis factor-α and interleukin-6 levels. The mice were then killed, and their spleen, liver, and bone marrow were examined microscopically for erythrophagocytosis. : After LPS administration, mouse Hgb and hematocrit levels dropped significantly. At 4 hours after LPS injection, all Hgb and hematocrit concentrations were found to be significantly lower compared with that of controls (P=0.002 and 0.001, respectively). Significantly increased concentrations of tumor necrosis factor-α and interleukin-6 were evident after LPS injection. Prominent hepatic erythrophagocytosis was observed in the LPS-injected mice compared with controls. A significant across-group difference was observed at 4 hours, driven by significantly higher values in group 500 mcg versus controls (P=0.005) and 100 mcg (P=0.025). A significant increase in erythrophagocytes was observed at 2 to 4 hours in the 500 mcg LPS group (P=0.044). : Erythrophagocytosis may play a role in anemia associated with acute infection in mice.
    Journal of Pediatric Hematology/Oncology 01/2013; 35(1):14-7. DOI:10.1097/MPH.0b013e31827b12ab · 0.90 Impact Factor
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    ABSTRACT: Objective: The epsilon gamma delta beta (εγδβ)-thalassemias are rare sporadic disorders caused by deletion of the β-globin gene cluster. The main clinical feature is marked prenatal and neonatal anemia that resolves spontaneously within a few months. Reports originating mainly from Europe have so far identified 30 such deletions The aim of the present work was to describe a novel 1.78-Mb deletion, the longest ever reported, and to detail the clinical features in 12 members of an extended Bedouin family. Methods: The deletion was identified by globin gene multiplex ligation-dependent probe amplification (MLPA) of the β-globin cluster and further characterized by comparative genomic hybridization. Past and present clinical and laboratory data of ten symptomatic and two asymptomatic patients were collected. Results: A 1.78-Mb εγδβ-deletion, the largest ever described, was identified in all patients. Although other genes were included in the deletion, no other symptoms were observed. Of the ten symptomatic fetuses and neonates, three died of the disease. The remainder required packed cell transfusions during the first months of life. Pregnancy complications included intrauterine growth restriction and oligohydramnios, as well as additional neonatal complications including prematurity and persistent pulmonary hypertension of the neonate. Conclusions: We suggest that εγδβ-thalassemia be added to the list of hemoglobinopathies that can cause neonatal anemia and that MLPA of the β-globin cluster be used to confirm its diagnosis. Careful surveillance during pregnancy is important to reduce neonatal mortality and morbidity, especially given the dramatic improvement that occurs later.
    European Journal Of Haematology 12/2012; 90(2). DOI:10.1111/ejh.12047 · 2.07 Impact Factor
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    ABSTRACT: Congenital dyserythropoietic anemia (CDA) is a rare group of red blood cell disorders with ineffective erythropoiesis and secondary hemochromatosis. Inappropriate suppression of hepcidin and high levels of growth differentiation factor 15 (GDF15) have been described in CDA I and II patients, probably contributing to secondary hemochromatosis. Hemojuvelin (HJV) is an important regulator of serum hepcidin, while soluble form of HJV (s-HJV) competitively down-regulates hepcidin. We determined the soluble hemojuvelin (s-HJV) levels in 17 patients with CDA I and in 17 healthy volunteers (HV) and looked for correlations with other parameters of iron overload and erythropoiesis. Significantly higher levels of s-HJV were found in patients (2.32 ± 1.40 mg/L) compared with healthy volunteers (0. 69 ± 0.44 mg/L) (P = 0.001). Western blot analysis confirmed the presence of high levels of s-HJV in CDA I patients. s-HJV positively correlated with serum ferritin, erythropoietin, soluble transferrin receptor, and GDF15 and negatively correlated with hepcidin to ferritin ratios. We for the first time documented high levels of serum s-HJV in CDA I patients, suggesting that it may contribute to iron loading pathology in CDA I and eventually in other anemias with ineffective erythropoiesis.
    European Journal Of Haematology 10/2012; 90(1). DOI:10.1111/ejh.12027 · 2.07 Impact Factor
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    ABSTRACT: Neutral lipid storage disease (Chanarin-Dorfman syndrome) is a rare autosomal recessive disorder of lipid metabolism, characterized by systemic accumulation of neutral lipids in multiple tissues. We report a case of a 14-year-old girl with generalized ichthyosis, liver cirrhosis, and a hearing impairment. A peripheral blood smear demonstrated marked cytoplasmatic vacuoles in most polymorphonuclear cells (Jordan's anomaly). Bone marrow examination revealed vacuoles in myeloid precursors. Genetic analysis showed that the patient was homozygous for the p.Arg312Ter mutation in the CGI-58 gene, a key enzyme in lipid metabolism. The peripheral blood smear is diagnostic, and should be performed in any patient with ichthyosis.
    Journal of Pediatric Hematology/Oncology 10/2012; 35(8). DOI:10.1097/MPH.0b013e318271c915 · 0.90 Impact Factor
  • Shraga Aviner · Ehud Even-Or · Hannah Tamary ·
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    ABSTRACT: Essential thrombocytosis (ET) is rare in children, sometimes difficult to be distinguished from secondary thrombocytosis. This report concerns 2 children with extreme thrombocytosis of 4100 × 10(9)/L and 1644 × 10(9)/L with partial and complete remission at 3 months and 4 years from diagnosis, with a follow-up of 4 and 17 years, respectively, with no cytoreduction therapy. Diagnosis of ET was suggested according to accepted criteria. However, spontaneous remission of the thrombocytosis argues for the diagnosis of secondary thrombocytosis. These patients highlight the complexity of distinguishing childhood ET from secondary thrombocytosis and the need for cautious personalized decision on cytoreduction therapy.
    Pediatric Hematology and Oncology 05/2012; 29(4):372-7. DOI:10.3109/08880018.2012.662712 · 1.10 Impact Factor
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    ABSTRACT: The diagnosis, treatment, and prognosis of immune trombocytopenic purpura (ITP) have been extensively studied, but data on its effect on health-related quality of life in children remain sparse. To shed more light on this issue, we administered the Kids' ITP Tools (KIT) questionnaire to 17 children with ITP attending a tertiary pediatric medical center and their parents (n=34). The mean KIT score was significantly lower in the parents' group than in the children's group (P=0.000). The main domains of concern for the parents were disease side effects and their child's future; the children were mostly concerned about the need to restrict physical activities. The presence of acute versus chronic disease had no impact on the KIT score in either group. These findings stress the need to develop different interventional programs for children with ITP and their parents to provide appropriate support to each.
    Journal of Pediatric Hematology/Oncology 01/2012; 34(1):2-5. DOI:10.1097/MPH.0b013e3182329b4f · 0.90 Impact Factor

Publication Stats

2k Citations
375.93 Total Impact Points


  • 1994-2015
    • Schneider Children's Medical Center of Israel
      Petah Tikva, Central District, Israel
    • The Children's Hospital of Philadelphia
      • Division of Hematology
      Philadelphia, Pennsylvania, United States
  • 2000-2014
    • Tel Aviv University
      • • Felsenstein Medical Research Center
      • • Sackler Faculty of Medicine
      Tell Afif, Tel Aviv, Israel
  • 2013
    • Edith Wolfson Medical Center, Holon
      Yerushalayim, Jerusalem, Israel
  • 2006
    • Universität Ulm
      • Department of Internal Medicine
      Ulm, Baden-Württemberg, Germany
    • Oxford University Hospitals NHS Trust
      Oxford, England, United Kingdom