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TheC/EBPEgene, located in 14q11.2, encodes for a B/zip-type transcription factor. The C/EBPɛ is involved in terminal differentiation and functional maturity of granulocyte progenitor cells and in cell apoptosis during myeloid differentiation. AC/EBPEgene has recently been described as a candidate gene involved in clinical variability of β-thalassemia (β-thal). In this study, theC/EBPEgene was sequenced in 146 subjects divided into the severe type of β-thal major (β-TM) and moderate type of β-thal intermedia (β-TI), and a control group. The analysis identified the rs45496295 (C > T) polymorphism in the heterozygous state in 73.9% β-TI patients, which was not the case in the β-TM patients or in the control group. Thus, the T allele is consequently associated with the β-TI group (p = 10−3). According to the Human Splicing Finder (version 3.0, Marseille, France), the presence of the rs45496295 polymorphism leads the creation of a new intronic exotic splicing enhancer (ESE) site. Moreover, the T allele of rs45496295 is associated with a lower transfusion regimen (p = 10−3) and a higher pretransfusion hemoglobin (Hb) rate (p = .006). The comparison of several factors concerning T allele carriers and non-carriers showed that the T allele does not act on the Hb F rate. The T allele of rs45496295, associated with moderate type of β-thal, seems to modify the C/EBPɛ action, thereby preventing the hemolysis. [ABSTRACT FROM AUTHOR]

Background: Von Willebrand's disease (VWD) is the most commonly inherited bleeding disorder. It is characterized by clinical, biological and molecular heterogeneity. In certain types of the disease, diagnosis can be difficult., Aim: We report the clinico-biological characteristics of VWD's patients and analyze diagnosis difficulties., Methods: 33 cases were diagnosed in the laboratoryfrom February to May, 2011. Screening hemostasis included the measuring of, Fviii: C, VWF: Ag and VWF: RCo. Blood cell count and blood group were performed in all cases., Results: Mean age at diagnosis is 13 years [10 months -43 years]. The sex ratio M/F is 0.5. The patients are classified type 3 VWD in 52% of the cases, type 2 VWD in 30 % of the cases and type 1 VWD in 18 % of the cases. The diagnosis of type 2B VWD suspected in combination of the ratio VWF:RCo / VWF: Ag <0,7 and thrombocytopenia in one case. Required tests for positive diagnosis and distinction between the primary categories of VWD are available. Specialized tests will allow a best characterization variants type 2 VWD for a better therapeutic approach.

Background: As a result of chronic hemolysis, hyperbilirubinemia is often observed, leading to the formation of pigment cholelithiasis which could be busted by the presence of uridine diphosphoglucuronosyltransferase 1A1 defects., Aim: Herein, we investigated the effect of glibert mutation on the occurrence of pigment cholelithiasis in Tunisian patients with beta (β) hemoglobinopathy including sickle cell anemia and β thalassemia (minor)., Subjects and Methods: Our study included 151 subjects divided in 75 SCA patients and 76 β thalassemia patients. Both groups of patients were divided into two sub-groups according to the presence or absence of cholelithiasis. The relationship between A(TA)nTAA variation of UGT1A1 gene, the serum bilirubin level and the occurrence of cholilithiasis was investigated., Results: Our results show a significant association between genotypes carrying variant (TA)7 and hyperbilirubinemia (p<0.05). Furthermore, we demonstrated a significant association between (TA)6/(TA)7 and (TA)7/(TA)7 genotypes with cholelithiasis among sickle cell anemia and thalassemia patients (p<0.05)., Conclusion: Altogether, our data provide evidence that genotypes (TA)6/(TA)7 and (TA)7/(TA)7 and (TA)7 variant present a risk factor of developing gallstone among β hemoglobinopathy Tunisian patients.

Background: Immunophenotyping is an essential step in the diagnosis of acute myeloid leukemia. Its prognostic value remains controversial with contradictory results., Aim: To assess prognostic impact of the immunophenotyping in AML., Methods: Our study is retrospective (October, 2005 - July, 2007) concerning 56 cases of AML (AML3 excluded) of the adult from 18 to 55 years old diagnosed and treated in Tunis Aziza Othmana Hospital. The immunophenotyping was performed by flow cytometry (Beckman Coulter EPICS XL MCL®). We studied clinical and biological characteristic, immunophenotypic expressions, and parameters of the response to the treatment: complete remission (CR), overall survival (OS), relapse free survival (RFS) and relapse in a delay of 1 year and 2 years. SPSS software was used to perform the statistical analysis., Results: The median age of the patients is of 37,7±11.8 years. Sex ratio (M/F) is 1.33. Among individual antigenic expressions, only CD7 is associated to lower CR rates (p=0.044). We did not find any statistically significant association between immunophenotypic expressions and OS nor with relapse or RFS., Conclusion: The impact of immunophenotyping in AML remains controversial because of contradictory results. The research of molecular changes would be an interesting alternative in our context.

Background: Sickle cell disease is an autosomal, recessive hemoglobinopathy characterized by hemolytic anemia. Red blood cell transfusions are uncommon therapeutic mainstay in sickle cell disease and repeated transfusions can result in iron overload. The predicted risks of iron overload and organ failure increase with both the duration of disease requiring transfusion therapy and the number of transfusions., Aim: To assess the state of iron overload in patients with sickle ce anemia according to their number of transfusions., Methods: The medical records of 94 patients with sickle cell anemia (46 had homozygous sickle cell disease, 41 had sickle-ß thalassemia, 7 had compound heterozygous hemoglobin: 4 SC and 3 SOArab) were retrospectively reviewed for the following: clinical exam, serum ferritin level, liver function tests, abdominal ultrasound exam and heart Doppler., Results: 61% of our patients are from the Northern- west of the country. The average age is 18.29 years (2 to 62 years) and the sexratio is 0.62. In addition to parental consanguinity which is found in 28.72% of the cases. The average level of ferritin is 660.35 ng/ml. 41.5% of the patients have a high status of ferritin witch ranged from 521.4 to 3360 ng/ml. There is not a significant difference of ferritin level according to age, sex and a phenotype of sickle cell anemia. However, it is higher among the transfused patients with a same phenotype (p<0.05). We found a correlation between serum ferritin levels and the number of transfusions (r =+0.74). Splenectomy has a preventive role because it allowed stopping the transfusion in 65% of the cases. The evaluation of organ dysfunction has found a hepatomegaly in 29% of the cases, half of witch were have a high status of serumferritin (> 1000 ng/ml). Left ventricular hypertrophy associated to valvulopathy was classified in 10 % of the cases., Conclusion: Iron overload in sickle cell anemia, though relying on transfusion, remains moderate. The repetitive assessment of serum ferritin level is considered as the best test though it does not evaluate an organic dysfunction. To evaluate them better, other tests are requiring: magnetic resonance imaging and Tc-Squid biosusceptometers.

Background: Thalassemia intermedia empasses a mild clinical and biological spectrum. The aim is to report the clinical and biological features and treatment of this disease., Methods: It is a retrospective study about 36 thalassemia intermedia patients (17 males, 19 females). Epidemiological, haematological aspects and treatment were reported, Results: The diagnosis was carried out at a relatively old age 15 years (1-72).The thalassemia intermedia was characterized by mild facial deformities, splenomegaly and moderate anemia ( Hb = 9.1 g/dl). The mean serum ferritin was 518 ng/ml (25-1800). Three phenotypes are caracterised: heterozygosis beta thalassemia, beta degrees thalassemia and beta + thalassemia. Clinical complications were hypersplenism, extra medullary hematopoiesis, leg ulcers, thrombosis and pulmonary hypertension. Treatment was based on occasionally transfusion and splenectomy on event of hypersplenious (47%). Evolution of this disease was generally good with a long lifespan at 31 years (6-83)., Conclusion: Thalassemia intermedia is well tolerated. Transfusions and splenectomy were indicated in case of hypersplenious.

Background: In inflammatory diseases, classical parameters of iron status (serum iron, serum ferritin, total iron-binding capacity of transferrin and transferrin saturation) are not very reliable., Aim: The purpose of this study is to investigate soluble transferrin receptor, its index and classical parameters of iron status [serum iron, serum ferritin, total iron-binding capacity of transferrin and transferrin saturation] during iron-deficiency anemia and combined iron deficiency and inflammatory anemia., Methods: Our study concerned 24 patients: 18 patients with iron-deficiency anemia and 6 patients with combined iron-deficiency and inflammatory anemia. 55 healthy subjects were included as controls. Both groups underwent classical parameters of iron status [serum iron, serum ferritin, total iron-binding capacity of transferrin and transferrin saturation] and measurement of soluble transferrin receptor with its index., Results: In iron-deficiency anemia, total iron-binding capacity of transferrin, soluble transferrin receptor and its index were enhanced, whereas serum iron, ferritinemia and transferrin saturation were low compared to controls. Compared to patients with iron-deficiency anemia, those with combined iron-deficiency and inflammatory anemia showed higher levels of serum iron and ferritinemia. In contrast, soluble transferrin receptor and its index did not vary significantly between both groups., Conclusion: Our findings show the interest of soluble transferrin receptor and its index in the detection of iron deficiency during anemia of inflammatory states.

Background: Splenectomy is frequently advised in hereditary hemolytic anemia. Severe complications could occur after splenectomy., Aim: To provide the indication and benefit of splenectomy, Methods: clinical and biological patterns were performed in a retrospective study of 82 patients: 17 homozygous beta thalassemia, 17 thalassemia intermedia, 33 heterozygote Hb/S beta thalassemia and 15 hereditary spherocytosis., Results: Splenectomy was performed for: Hypertransfusion in homozygous thalassemia, hereditary spherocytosis; hypersplenism in Thalassemia intermedia and splenic sequestration in heterozygote HbS/beta thalassemia. The benefit of splenectomy was proved in hereditary spherocytosis (100%), heterozygote HbS/beta thalassemia (90%) and thalassemia intermedia (75%); nevertheless in homozygous beta thalassemia. Post splenectomical complication are often thrombocytosis, thrombosis and infections., Conclusion: Splenectomy should be performed in hereditary hemolytic anemia to reduce and avoid transfusion.

Background: Hairy cell leukemia is a rare lymphoproliferative disorder., Aim: with cytological and immunophenotypic features., Methods: We report 6 cases of hairy cell leukemia diagnosed in the Biological Department of Hematology at the Aziza Othmana Hospital of Tunis., Results: Hairy cells was observed in blood smears of 5 cases. Flow cytometry analysis shown monoclonal a monoclonal population B while gatinting on the expression of the CD19 and SSC signal. The positivity of the CD103 is noted in 5 cases and the CD11c signal is intense in all the cases., Conclusion: Immunophenotype is of great interest in the diagnosis of hairy cell leukemia.

Background: Hemoglobin O Arab is a rare abnormal hemoglobin., Aim: We report the Clinical and biological features of this disease, Methods: 20 patients.:16 were compound hétérozygous Hb O Arab/Béta thalassemia and 4 homozygous Hemoglobin O Arab. Patients are 7 men and 13 women., Results: Most of them are originated from the North West of Tunisia with a age average of 39.7 years. Diagnosis was carried out at a relatively old age (26.9 years old). The homozygous form was not very symptomatic. The compound heterozygous form was more severe and characterized by a mild form of thalassemia with a moderate microcytic hypochromic anaemia (Hb = 8.8 g/dl). It was often complicated of thrombopenia due to hypersplenism in 40% of the cases. Treatment was based on occasionally transfusion and splenectomy on event of hypersplenism. Evolution of this disease was generally good with a long lifespan of patients., Conclusion: Haemoglobin O Arab is an abnormal hemoglobin well tolerated except for heterozygous category which requires iterative transfusions. Spelenectomy is indicated in case of hypersplenious. The evolution is generally good with a long survival.

Acute myeloid leukemia (AML)'s diagnosis is clinical and biological. We report here 80 AML with cytology and immunophenotype features to establish correlations. 21 AML1, 23 AML2, 12 AML3, 2 AML4, 18 AML5 and 3 AML6 were diagnosed by cytology. Only one case of AML0 was diagnosed by immunophenotype. Myelogysplasia is present in 29.8% cases. CD19 and CD56 expression was significantly associated to AML +t(8;21). Additionally, concomitant negativity of CD34 and HLA-DR was discrimininatif to AML3 diagnosis. Prognostic value to expression some CD needs time backwards.

Aim: was to provide the clinical and biological patterns hemoglobine disease in Tunisia., Methods: This retrospective study collected to 16 cases of hemoglobin C disease : 6 homozygotic Hb C and 10 heterozygotic Hb C/beta-thalassemia., Results: The clinical profile is characterized by mild hemolytic anemia (Hb = 11.7 g/dl) associated with splenomegaly and hypersplenism. Contrary to homozygous state, the Hb C/beta-thalassemia is associated with microcytosis and pseudopolycythemia. The diagnosis is based on target cells, specific intraerythrocytic Hb C crystals in blood smear and Hb C level at 100%., Conclusion: The Hb C disease must be considered as a benign hemoglobinopathy which is associated with a long survival without major complications.

The present work focuses on the therapeutic efficacy and the toxicity of alpha interferon in patients younger than age 18 years. 5 patients younger than 18 years were treated and followed up between 1990 and 1999 at the department of haematology (Aziza Othmana Hospital) Hydroxyurea was given as initial treatment to all patients. After a median period of 8 months, these patients received alpha interferon (5 millions units/m2 once). Six months after the beginning of the alpha interferon a complete hematologic response was obtained in all patients. The median overall survival was of 66 months: 3 patients are still alive (2 patients in an advanced stage and one patient in chronic phase) and 2 patients died after transformation. The most common reported side effects of alpha interferon were asthenia, weight loss, fever, myalgia, chills and headaches--these toxic manifestations were mild and were noticed in all our patients. Myelosuppression was noted in two patients. Interferon is well tolerated in patients younger than age years 18 old, with CML. It may offer an alternative to bone marrow transplantation in children in the chronic phase of CML without histocompatible donor. The role of new agents such as STI 571 needs to be evaluated as well.

Through a national retrospective study, the authors report the clinical and hematological characteristics of 124 acute lymphoblastic leukemia of the adult diagnosed during 5 years (1993-1997). The national prevalence is of 0.28/100.000 inhabitants/year. The sex-ratio is of 1.3. Sixty six per cent of patients were 16-35 years of age, and only 10% of them were more than 60 years of age. A tumoral syndrome was present at 71% of the cases with peripheral adenopathies in 55%, splenomegaly in 40%, hepatomegaly in 19% and a mediastinal tumor in 18% of the cases. The bone pain were rarely signaled (10%) and neuro-meningeal affection was found in only 3% of cases. There was no testicular lesions. The white blood cells count was less than 30.000/mm3 in 60% whereas an important hyperleucocytosis superior than 100.103/mm3 was observed in 20% of the cases. Anemia and thrombopenia were noted in 94% and 90% of the cases respectively. Acute lymphoblastic leukemia typing by cytological study of Bone marrow according to the Fransh-American-Britain criteria (FAB) had found 43%, 48% and 4% for type 1,2 and 3 respectively. In 5% of the cases the type of the acute lymphoblastic leukemia was not precised (diagnosis based on the Bone biopsy).