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Resume La fibrillation atriale est une situation clinique qui peut exposer a un risque de complications thromboemboliques. Plusieurs marqueurs biologiques ont ete testes afin d’affiner la stratification de ce risque. Le but de cette etude est d’etudier l’interet du dosage des d -dimeres dans cette pathologie. L’etude etait prospective, interessant 50 malades et 19 temoins colliges au service de cardiologie de l’hopital Mongi Slim entre le 1er juillet–1er novembre 2012. Le dosage des d -dimeres a ete realise sur mini-VIDAS® et analyse en fonction des donnees cliniques, echographiques et biologiques. L’âge moyen des patients etait de 61,8 ± 10,6 ans. Le score CHA2DS2-VASc moyen etait de 2,58 ± 1,31. Le taux moyen des d -dimeres des patients etait de 590 ± 506 ng/mL et de 225,26 ± 112,95 ng/mL chez les temoins (p = 0,02). Il n’a pas ete retrouve de difference significative entre le taux des d -dimeres selon l’âge, le sexe, le type et l’etiologie de la fibrillation atriale, le score CHA2DS2-VASc, la surface de l’oreillette gauche et la presence d’un thrombus intra-auriculaire gauche. Le taux des d -dimeres etait significativement plus eleve chez les patients sous acenocoumarol ayant un INR d -dimeres (300 ng/mL) a ete determinee permettant de distinguer significativement les patients des temoins (p d -dimeres pourrait permettre d’identifier les patients en fibrillation atriale avec un etat d’hypercoagulabilite. Il pourrait etre complementaire au dosage de l’INR dans la surveillance du traitement anticoagulant et ceux en permettant d’affiner le risque thrombogene.

International audience; The pro-inflammatory context of sickle cell disease promotes the liberation of cytokines such as CCL5, encoded by a gene located on chromosome 17. Herein, the occurrence of three variations of CCL5 in sickle cell anemia (SCA) and their relations to two major complications - painful crisis and presence of infections - were investigated. 100 SCA Tunisian patients and 100 healthy subjects were included in the case control study. Then the sample of patients was divided into two groups according to the presence or absence of each complication. The polymorphisms, namely g.-403G>A, g.-28C>G and g.In1.+1T>C, were analyzed by PCR/sequencing. Our findings show the presence of eight genotypes, namely GG, GA and AA of g.-403G>A, CC, CG and GG of g.-28C>G, and TT and TC of g.In1.+1T>C. The frequencies of studied single nucleotide polymorphisms (SNPs) and haplotypes in SCA patients do not differ significantly from healthy control group results. There is also no significant association between the analyzed polymorphisms and complications as for painful crisis and presence of infections (p > 0.05). Altogether, our data support the conclusion that the three polymorphisms of CCL5, namely g.-403G>A, g.-28C>G and g.In1.+1T>C, do not seem to be involved in the clinical variability of SCA in Tunisia.

Auteur(s) : Wijden El Borgi1, Emna Gouider1, Nour Louati1, Nawel Ben Salah1, Halima Senana2, Ramzi Jeddi3, Ali Saad2, Raouf Hafsia1 1Service d’hematologie biologique, Hopital Aziza Othmana, Tunis 2Service de cytogenetique, Hopital Farhat Hached, Sousse 3Service d’hematologie clinique, Hopital Aziza Othmana, Tunis, Tunisie L’hemophagocytose par les cellules blastiques est rarement observee au cours des leucemies aigues (LA) myeloides, elle est surtout rapportee dans les [...]

International audience; Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders characterized by sustained and otherwise unexplained overproduction of eosinophils with organ involvement and consecutive dysfunction. Detection of the FIP1L1-PDGFRA fusion gene or the corresponding cryptic 4q12 deletion in HES supports the diagnosis of chronic eosinophilic leukemia (CEL) and provides a molecular explanation for the pathogenesis of this disorder. We screened seven Tunisian patients fulfilling the WHO criteria of HES for the presence of the FIP1L1-PDGFRA fusion gene using nested reverse transcription polymerase chain reaction on peripheral blood samples. Four of the seven patients were positive for this fusion gene. Sequence analysis revealed a substantial heterogeneity of the fusion transcripts due to the involvement of several FIP1L1 exons. All patients were male. The median age at diagnosis was 24 years (range, 18-50); one patient had a history of hypereosinophilia of more than 10 years. Two patients had clinically important and symptomatic eosinophilic endomyocardial disease with thrombotic events. Splenomegaly was constant in FIP1L1-PDGFRA positive CEL but not in the other HES patients (only 1/3).; Les hyperéosinophilies essentielles sont caractérisées par une hyperéosinophilie supérieure à 1500 éléments/mm 3 persistante au-delà de sixmois, après exclusion d ’ une éosinophilie réactionnelle. Différentes altérations viscérales peuvent s’y associer leur pronostic est souvent redou-table et jusqu’à une période récente, il n’existait pas de traitement spécifique ou réellement efficace. En 2003 un gène de fusion :FIP1L1-PDGFR alpha a été retrouvée de façon récurrente dans ces syndromes, ce gène de fusion est généré à la suite d’une délétion interstitielle en 4q12 qui est cryptique à l’ analyse cytogénétique standard, la protéine chimérique résultante a une activité tyrosine kinase constitutive qui répond au traitement par l’ imatinib utilisé par ailleurs pour le traitement de la leucémie myéloïde chronique. Nous rapportons quatre cas d’hyperéosinophilie associéesà ce remaniement génétique

Thiamine-responsive megaloblastic anaemia (TRMA) syndrome with diabetes and deafness was found in two patients from a Tunisian kindred. The proband was homozygous for a novel mutation, 287delG, in the high-affinity thiamine transporter gene, SLC19A2. We demonstrated that fibroblasts from this patient exhibited defective thiamine transport. These data confirm that the SLC19A2 gene is the high-affinity thiamine carrier and that this novel mutation is responsible for TRMA syndrome.

We report two cases of atypical defibrination syndromes in patients with respectively acute monoblastic leukemia (chronic myeloid leukemia initially) and acute lymphoblastic leukemia. Hemostasis studies show low fibrinogen level, elevated D-dimers, decreased alpha 2 antiplasmin and factor V, normal antithrombin III values. Plasminogen is below the normal range in one patient. Soluble complexes, which are an important argument for diagnosis of intravascular coagulation disease, are not detected in both patients. Primary or secondary hyperfibrinolysis seems also excluded since euglobulin clot lysis time was normal. Enzymatic proteolysis of fibrinogen (or fibrin) by the blast cells has been reported by some authors; this mechanism could account for the hemostasis abnormalities observed in these two patients.

Les leucemies aigues lymphoblastiques (LAL) sont des hemopathies malignes se definissant par l'envahissement de la moelle par une population lymphoide immature et monoclonale. L'etude de la maladie residuelle (MRD) au cours de ces hemopathies permet d'evaluer la reponse therapeutique. L'objectif de notre travail est l'evaluation de la masse tumorale residuelle a la fin du traitement d'induction (J35). Cette etude porte sur 59 patients suivis au service d'hematologie de l'Hopital Aziza Othmana. A J35, l'estimation d'une remission complete est basee sur une etude cytologique. Elle est definie par un taux de blastes < 5 %. L'etude immunophenotypique a objective 42 cas de LAL B et 17 cas de LAL T. La MRD est < 10 -4 dans 29 % des cas seulement. Ce taux reste inferieur a celui rapporte dans les differentes series de la litterature (60-70%). L'immunophenotypage permet de quantifier les blastes non detectables en cytologie, d'evaluer la masse tumorale residuelle et d'adapter les protocoles therapeutiques. La cytometrie en flux est une technique simple, rapide, tres sensible et moins couteuse que la biologie moleculaire dans l'evaluation de la maladie residuelle et permet ainsi un suivi therapeutique rigoureux des patients.

Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders characterized by marked peripheral blood and tissue eosinophilia resulting in organ damage. Recent advances in molecular biology have led to the identification of a FIP1L1-PDGFRA fusion gene as a recurrent abnormality in some patients with HES. This fusion gene results from a cryptic 4q12 interstitial deletion involving an 800 kb region. Recent reports indicate that this subtype of HES is imatinib responsive with rapid and complete haematological remissions. Here we report two patients successfully treated with imatinib.

Stroke is a devastating and potentially fatal complication to sickle cell Anemia. Strokes are difficult to explain on the basis of the central pathological process in SCA, namely the occlusion of small vessels by deformed sickled cells. We examined whether Single Nucleotide Polymorphism (SNP) variants in the MCP-1 or CCR2 genes independently or in combination are associated with occurrence of Cerebrovascular Accidents (AVC) in SCA Tunisian patients. Material and methods: 100 SCA patients among whom 19 have AVC were enrolled in this study. Clinical diagnosis of stroke was performed by the use of Transcranial Doppler ultrasonography (TCD). The genotyping of rs1026611 in the MCP-1 gene and V64I of CCR2 was performed using PCR/RFLP. Results: Our findings showed no association of the polymorphisms studied with occurrence of AVC in SCA Tunisian patients.

Immunophenotyping is a major tool for the diagnosis of the chronic lymphoid leukaemia (CLL). Its interest remains limited in the classification of the other B chronic lymphoproliferative syndromes (B-CLPS). We evaluate the place of the flow cytometry (CMF) in the diagnosis and classification of the non CLL B-CLPS. The cases with Matutes score of 4 or more are excluded. A confrontation of the results to the histology is made. 28 cases of non CLL B-CLPS are diagnosed. CMF shows a κ monoclonal population in 15 cases and λ in 13 cases. A co-expression CD19+CD5 + is found in 11 cases concording with an atypic CLL or a mantel cell lymphoma in 6 cases with Matutes score of 3. In 5 cases, we concluded to non CLL B-CLPS (Matutes

International audience; AIMS: The skeletal manifestations of sickle cell disease are the result of changes in bone and bone marrow caused by chronic tissue hypoxia that is exacerbated by episodic occlusion of the microcirculation by the abnormal sickle cells. Furthermore, the occurrence of osteonecrosis is under the control of some modifier gene. BMP6 (Bone morphogenetic protein) has been reported as associated with osteonecrosis in sickle cell anemia (SCA). Herein, we intend to study the impact of rs267196, rs267201, rs408505 and rs449853 of BMP6 gene in the occurrence of osteonecrosis among sickle cell patients in Tunisia. METHODS: Our study involved 100 SCA patients among whom 19 have osteonecrosis of the head of the femur. The latter polymorphisms of BMP6 gene were analyzed for all subjects by PCR/sequencing. To test for trait association with the candidate SNPs, genotype and allele frequencies between cases (osteonecrosis group) and controls (non-osteonecrosis group) were compared using Pearson's chi_square test with a significance threshold of P

We screened 423 patients referred to our laboratory after hemolysis triggered by fava beans ingestion, neonatal jaundice or drug hemolysis. Others were asymptomatic but belonged to a family with a history of G6PD deficiency. The determination of enzymatic activity using spectrophotometric method, revealed 293 deficient (143 males and 150 females). The molecular analysis was performed by a combination of PCR-RFLP and DNA sequencing to characterize the mutations causing G6PD deficiency. 14 different genotypes have been identified : G6PD A(-) (376A>G;202G>A) (46.07%) and G6PD Med (33.10%) were the most common variants followed by G6PD Santamaria (5.80%), G6PD Kaiping (3.75%), the association [c.1311T and IVS11 93c] (3.75%), G6PD Chatham (2.04%), G6PD Aures (1.70%), G6PD A(-) Betica (0.68%), the association [ 376G;c.1311T;IVS11 93c] (0.68%), G6PD Malaga, G6PD Canton and G6PD Abeno respectively (0.34%). Two novel missense mutations were identified (c.920A>C: p.307Gln>Pro and c.968T>C: p.323 Leu>Pro). We designated these two class III variants as G6PD Tunis and G6PD Nefza. A mechanism which could account for the defective activity is discussed.

In Tunisia, the ATRA era began in 1998 with the use, consecutively, of two regimens combining ATRA and an anthracycline with cytarabine (APL93), and without cytarabine (LPA99). From 2004, 51 patients with confirmed APL either by t(15;17) or PML/RARA were treated according to the PETHEMA LPA 99 trial. Forty three patients achieved CR (86%). The remaining seven patients had early death (one died before treatment onset): four caused by differentiation syndrome (DS) and three died from central nervous system hemorrhage. Multivariate analysis revealed that female gender (P=0.045), baseline WBC> 10 G/L ( P=0.041) and serum creatinine > 1.4mg/dl ( P=0.021) were predictive of mortality during induction. DS was observed in 16 patients (32%) after a median onset time of 15 days from treatment onset (range, 2–29). Body mass index ≥ 30 (P=0.01) was the only independent predictor of DS. Occurrence of hypertensive peaks significantly predicted occurrence of DS (P=0.011) and was significantly associated with high BMI (p=0.003). With a median follow-up of 50 months, 5 year cumulative incidence of relapse, event free and overall survival were 4.7%, 74% and 78%, respectively.

Background: Hemophilia is a hereditary bleeding disorder characterized by a deficiency of factor VIII (hemophilia A) or factor IX (hemophilia B). It is established that hemophilia is a ubiquitous condition that affects one birth in 10,000, regardless of race or geographic region. We propose in this work to assess the incidence of hemophilia in the North of Tunisia with a literature review. The hemophilia treatment center at the hospital Aziza Othmana supports patients in northern Tunisia, which represents 60% of all tunisians cases. The estimated number of inhabitants is 5.19 million (50% of the country population). Methods: Assays of factors VIII and IX are performed by STA Compact, Stago®. Confirmation of the diagnosis ismade on two different samples. Results: Twenty cases of hemophilia were diagnosed between January 2010 and December 2011 in our center. The average of age was 3.37 years (2 months-28 years). The most frequent circumstances of diagnosis are hematomas and hemarthrosis following minor trauma (12 cases). Family history of hemophilia is found in 6 cases. For all patients, an isolated prolonged APTT with a correction to the mixture test was found. We note 15 cases of hemophilia A and 5 cases of hemophilia B. The distribution of cases according to severity is: severe (9 cases), moderate (8 cases) and minor (3 cases). Comment: The incidence of hemophilia on the north of Tunisia is 1.1cases per 10 000 births per year. The incidence found in our series corresponds to the incidence reported in the literature. However, the prevalence of hemophilia diagnosed in Tunisia remains low only 50% of the theoretical number of hemophilia is diagnosed.