Establishment of reference values for prothrombin time, activated partial thromboplastin time and fibrinogen in adults in Burkina Faso.

The ordering of clinical haemostasis tests is increasing in Burkina Faso due to the newly emergence of cardiovascular and metabolic diseases. However, appropriate local reference values (RV) are lacking. Our study aimed to establish RV for prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen assays. In 2020, we carried out a cross-sectional study at the transfusion centre of Ouagadougou and included 280 healthy blood donors (140 males and 140 females) as reference subjects (RS) according to CLSI guidelines (C28 A3). From each RS a 5 mL blood sample had been withdrawn in citrated tubes. We performed PT, aPTT and fibrinogen assays using the Sysmex™ CA660 coagulometer and Siemens™ reagents. RV were calculated using the "central 95 percentile" method. Reference values of PT, aPTT and Fibrinogen were respectively [73.84%-117.50%], [20,01-29.45] seconds and [2.04-3.83] g/L for females and [58.81%-112,31%] seconds, [20,9-29,98] seconds and [1.58-3.35] g/L for males. We report for the first time locally appropriate haemostasis RV for the Burkina Faso adult's population. They will be of clinical use to our health care professionals.

Red blood cell alloantibodies in paediatric transfusion in sub-Saharan Africa: A new cohort and literature review.

Blood transfusion support predisposes transfused children to the risk of erythrocyte alloimmunization in Sub-Saharan Africa. A cohort of 100 children receiving one to five blood transfusions were recruited for screening and identification of irregular antibodies using gel filtration technique. The mean age was 8 years and the sex-ratio at 1.2. The retrieved pathologies were: major sickle cell anaemia (46%), severe malaria (20%), haemolytic anaemia (4%), severe acute malnutrition (6%), acute gastroenteritis (5%), chronic infectious syndrome (12%) and congenital heart disease (7%). The children presented with haemoglobin levels ≤6 g/dl, and 16% of them presented positive irregular antibodies directed against the Rhesus (30.76%) and Kell (69.24%) blood group systems. A literature review shows that irregular antibody screenings vary from 17% to 30% of transfused paediatric patients in Sub-Saharan Africa. These alloantibodies are in particular directed against the Rhesus, Kell, Duffy, Kidd and MNS blood group and generally found in sickle cell disease and malaria. This study highlights the urgent need of extended red blood cell phenotyping including typing for C/c, E/e, K/k, and Fya/Fyb, and if possible Jka/Jkb, M/N, and S/s for children before transfusion in Sub-Saharan Africa.

Epstein-Barr virus reactivation induces MYC-IGH spatial proximity and t(8;14) in B cells.

Burkitt lymphoma (BL) is a B cell malignancy associated with the Epstein-Barr virus (EBV). Most BL cases are characterized by a t(8;14) chromosomal translocation involving the MYC oncogene and the immunoglobulin heavy chain gene (IGH). The role of EBV in promoting this translocation remains largely unknown. Here we provide the experimental evidence that EBV reactivation from latency leads to an increase in the proximity between the MYC and IGH loci, otherwise located far away in the nuclear space both in B-lymphoblastoid cell lines and in patients' B-cells. Specific DNA damage within the MYC locus, followed by the MRE11-dependent DNA repair plays a role in this process. Using a CRISPR/Cas9-based B cell model to induce specific DNA double strand breaks in MYC and IGH loci, we have shown that the MYC-IGH proximity induced by EBV reactivation leads to an increased t(8;14) translocation frequency.

Transfusion Practice, Post-Transfusion Complications and Risk Factors in Sickle Cell Disease in Senegal, West Africa.

CONTEXT AND OBJECTIVES: Blood transfusions (BT) remain a mainstay of therapy for patients with sickle cell disease (SCD) but pose significant clinical challenges. We aim to assess infectious markers, red cell alloimmunization, and iron overload secondary to BT in SCD patients. MATERIALS AND METHODS: This case-control study included 253 SCD (153 SCD-transfused and 100 SCD non-transfused). We evaluated the transfusion practice (modalities, indications), post-transfusion complications (infections, alloimmunization, iron overload), and risk factors of these complications (socio-demographic, clinical, biological). RESULTS: Median age was 28.5 years (5 - 59). The sex ratio was 0.86. Homozygous SCD was the most common (95.3%). Simple BT was performed in 92.8% and transfusion exchange in 18.9%. Transfusion indications were dominated by acute anemia (57.06%) and vaso-occlusive crisis (VOCs) (14%). Red blood cell concentrates (RBCSs) were administered to 93.46%. The median RBCs received per patient was 10 (2 - 48). The prevalence of VHC in SCD-transfused was 1.33% and 2% for VHB. Anti-HIV antibodies were not found. Red cell alloimmunization frequency was 16%. The most common alloantibodies were anti-rhesus (34.19%) and anti-Kell (23.67%). Iron overload was detected in 7.84%. The number of RBCs transfused was the only risk factor for alloimmunization (p = 0.03) and iron overload (p = 0.023). BT frequency was not related to infectious transmission. CONCLUSION: BT therapy is still a risk for SCD polytransfused patients despite advances in blood safety. Although infectious transmission has rare, the risk of alloimmunization and iron overload is high in these patients.

Smudge cells percentage on blood smear is a reliable prognostic marker in chronic lymphocytic leukemia

Abstract Objective We evaluated the relevance of using the smudge cell percentage in the blood smear as a prognostic marker in CLL. Methods In this prospective study, 42 untreated Senegalese patients with CLL were enrolled. The diagnosis was established, based on the peripheral blood count and flow cytometry using the Matutes score. Cytogenetic aberrations, assessed by fluorescence in situ hybridization (FISH), were available for 30 patients, while the immunoglobulin heavy chain genes (IGVH) mutation status was performed by next-generation sequencing (NGS) in 24 patients. The SC percentage was determined in the blood smear, as previously described. Statistical analyses were executed using the GraphPad Prism 8. Results The mean age was 63 years (48 - 85) and the male: female sex ratio was 4.66. A low SC (< 30%) percentage was correlated with Binet stage B/C (p= 0.0009), CD38 expression (p= 0.039), unmutated IGVH status (p= 0.0009) and presence of cytogenetic abnormalities (for del 13q, p= 0.0012, while for other cytogenetic aberrations, p= 0.016). An inverse correlation was found between the SC percentage and the absolute lymphocyte count (r= -0.51) and patients with higher percentage of SCs had a prolonged survival. However, there was no correlation between the SC percentage and age (p= 0.41) or gender (median, 19% for males vs. 20% for females; p= 0.76). Conclusion When less than 30%, the SC was associated with a poor prognosis in CLL. Easy and affordable, the percentage of SCs in a blood smear could be a reliable prognostic marker, accessible to all CLL patients, mainly those in developing countries.

Smudge cells percentage on blood smear is a reliable prognostic marker in chronic lymphocytic leukemia.

OBJECTIVE: We evaluated the relevance of using the smudge cell percentage in the blood smear as a prognostic marker in CLL. METHODS: In this prospective study, 42 untreated Senegalese patients with CLL were enrolled. The diagnosis was established, based on the peripheral blood count and flow cytometry using the Matutes score. Cytogenetic aberrations, assessed by fluorescence in situ hybridization (FISH), were available for 30 patients, while the immunoglobulin heavy chain genes (IGVH) mutation status was performed by next-generation sequencing (NGS) in 24 patients. The SC percentage was determined in the blood smear, as previously described. Statistical analyses were executed using the GraphPad Prism 8. RESULTS: The mean age was 63 years (48 - 85) and the male: female sex ratio was 4.66. A low SC (< 30%) percentage was correlated with Binet stage B/C (p = 0.0009), CD38 expression (p = 0.039), unmutated IGVH status (p = 0.0009) and presence of cytogenetic abnormalities (for del 13q, p = 0.0012, while for other cytogenetic aberrations, p = 0.016). An inverse correlation was found between the SC percentage and the absolute lymphocyte count (r = -0.51) and patients with higher percentage of SCs had a prolonged survival. However, there was no correlation between the SC percentage and age (p = 0.41) or gender (median, 19% for males vs. 20% for females; p = 0.76). CONCLUSION: When less than 30%, the SC was associated with a poor prognosis in CLL. Easy and affordable, the percentage of SCs in a blood smear could be a reliable prognostic marker, accessible to all CLL patients, mainly those in developing countries.

Homozygous sickle cell disease related mortality in Senegal (2011-2020).

Homozygous sickle cell disease (HSCD) is characterized by multiorgan morbidity and an increased risk of early death. We aim to describe the mortality rate, causes, and risk factors of death in HSCD between 2011 and 2020. We conducted a retrospective study with a duration of 10 years in the cohort of 2348 HSCD patients. The mortality rate was determined by reporting the number of deaths to the total number of patients followed in the year. Sociodemographic, clinical, biological data and causes of death were studied. Death risk factors were determined by a bivariate analysis comparing deceased and living HSCD patients. The mean age of death was 26 years (3-52). The sex ratio was 1.2. The mortality rate was 2.76%. The death rate was high in 2011 (3.2%) and low in 2020 (0.17%). We observed a significant reduction of mortality of 94.6%. Most of the common causes of death were acute anemia (40%), acute chest syndrome (24.6%), and infections (20%). Risk factors of death were age, vaso-occlusive crises ≥3, acute chest syndrome, blood transfusion, and chronic complications. Mortality among HSCD has significantly decreased over the past 10 years in Senegal, and the main causes of death were acute anemia, acute chest syndrome, and infections.

[Primary cutaneous localization revealing leukemia/T-cell lymphoma associated with chronic HTLV-1 infection in a adult. A case presentation]. / Localisation cutanée révélatrice d'une leucémie/lymphome T de l'adulte.

Adult T-cell leukemia/lymphoma (ATLL) is a rare medical condition and a diagnosis that ought to be considered for patients living in an area endemic for the HTLV-1 virus (human T-lymphotrophic virus) where a T-cell lymphoproliferative diagnosis has been made. The cutaneous clinical forms may be the first manifestation of the disease. We report here an observation in a 60-year-old Senegalese woman whose skin lesions were sampled to reveal the ATLL immunophenotypic profile CD4+, CD25+, FoxP3-, and CD7-. HTLV-1 seropositivity confirmed the histopathological diagnosis, and should be corroborated by demonstration of a molecular clonal rearrangement by PCR (Polymerase Chain Reaction). This is a problem because such techniques are not always available in Africa.

Challenges in the management of sickle cell disease during pregnancy in Senegal, West Africa.

OBJECTIVES: The aim of this study was to evaluate the maternal and fetal complications in pregnant patients with sickle cell disease (SCD) and find risk factors of stillbirth. METHOD: We conducted a prospective study in pregnant women with SCD. Demographic characteristics, maternal and fetal morbi-mortality, and outcome of pregnancies were described. Risk factors of fetal loss were evaluated by comparing the parameters of the pregnancies that led to a live birth with those interrupted. RESULTS: We included 70 pregnancies in 58 women with SCD. The average age was 29.3 years. The average gestational age at the start of follow-up was 13 weeks. The occurrence of acute complications was significantly higher during pregnancy compared to the year before (p < 0.05). Maternal mortality was 0%. Live birth rate was 80%. Fetal loss rate was 3.9 times higher in previous pregnancies that had not been monitored in hematology (71.8 versus 18.6%). Stillbirth was associated with nulliparity, high leukocytes or platelet counts (p < 0.05). CONCLUSION: Pregnancy in SCD was associated with a high maternal morbidity and stillbirth. Nulliparity, high leucokocytes or platelet count were identified as risk factors of fetal loss.

Preferential Usage of Specific Immunoglobulin Heavy Chain Variable Region Genes With Unmutated Profile and Advanced Stage at Presentation Are Common Features in Patients With Chronic Lymphocytic Leukemia From Senegal.

OBJECTIVES: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western populations, being rarer in Asian and African people. It has been suggested that patients with CLL from Africa might have a more aggressive disease compared with white patients. In this study, we aimed to identify genetic factors that may account for this difference. METHODS: We analyzed immunoglobulin heavy chain (IGH) genes' mutational status by performing next-generation sequencing in 25 Senegalese and 50 Italian patients with CLL. RESULTS: We found that Senegalese patients more frequently had adverse prognostic factors and an unmutated profile. Furthermore, we documented that IGHV1 (IGHV1-69), IGHD3, and IGHJ6 were significantly more frequent in Senegalese patients, whereas IGHV3-30 was common and limited to the Italian cohort. Stereotyped receptors commonly detected in the white population were not recorded in our Senegalese series. CONCLUSIONS: The different IGH repertoire we observed in the Senegalese cohort may reflect the diverse genetic and microenvironmental (ie, polymicrobial stimulation) background.

Bleeding risk assessment in hemophilia A carriers from Dakar, Senegal.

: Hemophilia A carriers have an abnormal X chromosome with a molecular abnormality of FVIII gene. These carriers, long considered to be free of bleeding risk, could have the same symptoms as mild hemophiliacs. This study aim to assess bleeding risk of hemophilia A carriers monitored at the Clinical Hematology Department of Dakar. This is a prospective study of a period of 6 months including 22 hemophilia A carriers aged between 8 and 48 years. Hemophilia carriers were recruited using the genealogical tree of hemophiliacs followed in the service. Their diagnosis was carried out by long range PCR and Sanger sequencing method searching the molecular abnormality responsible for hemophilia in their family. Bleeding risk was determined using a questionnaire consisting of different bleeding symptoms quoted from -1 to 4 according to the severity. Total of different values allow to determine the bleeding score which was pathological if it was greater than or equal to 1. Medium age was 22.5 years (8-48) (SD = 9.28). Four hemophilia A carriers (18.1%) presented bleeding symptoms and had a bleeding score at least 1 (P = 0.02). Menorrhagia was predominant (13.6%) followed by epistaxis (9%), gingivorrhagia (9%), and prolonged bleeding after tooth extraction (9%). Factor VIII level was lower in hemophilia carriers who presented bleeding (42 ±â€Š8.61 UI/l) versus hemophilia carriers without bleeding (100 ±â€Š50.95 UI/l) (P = 0.001). There was no significant correlation between bleeding occurrence and age (P = 0.81), activated patial thromboplastin time value (P = 0.97) and FVIII/Von Willebrand Factor ratio (P = 0.12). One in five hemophilia carriers presented bleeding and the questionnaire was effective to identify hemophilia carriers who had a risk of bleeding.

Circumcision in hemophilia using low quantity of factor concentrates: experience from Dakar, Senegal.

BACKGROUND: Circumcision in hemophiliacs is a delicate surgery because of bleeding risks that could be avoided by adequate substitution of coagulation factor. This practice is very challenging in countries where anti hemophilic treatment is inaccessible. The study aimed to evaluate a circumcision protocol in hemophilia A using low quantities of factor concentrates. METHODS: This prospective study included 26 hemophiliacs A who underwent circumcision in 2014. Medical treatment protocol using low quantity of factor concentrates was drafted by physicians of the Hemophilia Treatment Center and the surgical protocol by experienced surgeons. Assessment criteria were: number of hospitalization days, number of exposure days to factor concentrates, delay to healing and occurrence of bleeding events. RESULTS: Mean age was 9.6 years (1-30). Hemophiliacs patients were classified as severe (n = 8), moderate (n = 9) and mild form (n = 9). Mean number of exposure days to factor VIII concentrates was 6.9 days (5-12) in children and 10.75 days (7-16) in adults (p = 0.0049); mean number of hospitalization days was 3.68 days (2-10) in children and 13.5 days (13-15) in adults (p = 0.0000); delay to healing was 26.47 days (20-35) in children and 25.25 days (22-30) in adults (p = 0.697); five haemophiliacs (19.2%) presented bleeding events after the circumcision. The mean amount of FIII concentrates used per patient was 1743 IU (810-2340). CONCLUSION: The study shows treatment protocol using low quantity of factor concentrates is efficient in hemophilia patients who underwent circumcision.

Pattern of chronic myeloid leukemia in the imatinib era in a Sub-Saharan African setting.

Chronic myeloid leukemia (CML) is an orphan disease in Africa because of the inaccessibility to specific treatment and the high cost of diagnosis and monitoring patients. The aim of this study was to report CML treatment response in a developing country in the tyrosine kinase inhibitor era. We conducted a longitudinal study of our cohort of CML patients. Socio-demographic, diagnosis, therapeutic, and treatment response parameters were studied. Sokal score, disease phase at diagnosis, delay from diagnosis to treatment, and treatment response were analyzed for their impact on survival. Fifty-five patients with a diagnosis of CML and who received treatment with imatinib for a minimum of 3 months were included in this study. Median follow-up was 170 patient-years. The sex ratio (M/F) was 1.62 and median age at diagnosis was 42 years. At diagnosis, 85.5 % of the patients were in chronic phase (CP), 12.7 % in accelerated phase (AP), and 1.8 % in blast crisis (BC). Sokal risk score distribution was as follows: low risk 29.8 %, intermediate risk 38.3 %, and high risk 31.9 %. Median time from first symptoms to first medical visit was 6.2 months and median time from first medical visit to cytogenetic and or molecular confirmation was 12.4 months. Mean delay time from first medical visit to imatinib initiation was 12.5 months (95 % CI 6.3-18.7). The complete hematologic response (CHR) at 3 months, the major cytogenetic response (MCR) at 12 months, and the major molecular response (MMR) at 24 months were respectively 82.4, 75, and 25 %. The 2-year overall survival rate was 81 %. Advanced phase at the diagnosis, discontinuation of imatinib therapy over 15 % of the time, lack of CHR at 3 months, lack of MCR at 12 months, and progression of the disease during imatinib therapy were associated with a risk of death (p ≤ 0.05). Our data confirm the improved prognosis of CML treated with imatinib in the setting of a developing country. However, response rates are lower than in developed countries, and additional efforts should be made to facilitate early diagnosis and improve access to TKI, treatment compliance, and regular molecular monitoring of patients.

Characteristics of chronic lymphocytic leukemia in Senegal.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a mature B-cell neoplasm characterized by the expansion of CD5-positive lymphocytes in peripheral blood. While CLL is the most common type of leukemia in Western populations, the disease is rare in Africans. Hence, clinical and laboratory data and studies of CLL in Sub Saharan populations have been limited. The aims of this study were to analyze the characteristics of senegalese patients with CLL at the time of the diagnosis and to identify the correlation between clinical characteristics (Binet stage) with age, gender, laboratory parameters and chromosomal abnormalities. METHODS: In this study, we investigated the clinical and laboratory characteristics of CLL in Senegal. A total of 40 patients who had been diagnosed with CLL during the period from July 2011 to April 2015 in Senegal were evaluated. Cytology and immunophenotype were performed in all patients to confirm the diagnosis. The prognosis factors such as Binet staging, CD38 and cytogenetic abnormalities were studied. The statistical analysis was performed using STATA version 13 (Stata college station Texas). Each patient signed a free and informed consent form before participating in the study. RESULTS: The mean age was 61 years ranged from 48 to 85. There were 31 males and only 9 females (sex ratio M : F = 3,44). At diagnosic, 82.5 % of the patients were classified as having advanced Binet stages B or C. The prognosis marker CD38 was positive in 28 patients. Cytogenetic abnormalities studied by FISH were performed in 25 patients, among them, 68 % (17 cases) had at least one cytogenetic abnormality and 28 % had 2 simultaneous cytogenetic abnormalities. CONCLUSION: Africans may present with CLL at a younger age and our data suggest that CLL in Senegal may be more aggressive than in Western populations.

Rosai Dorfman disease diagnosed by fine-needle aspiration cytology in a young man with HIV infection.

RDD (Rosai Dorfman disease) is a rare and benign histiocytic proliferative disorder of unknown etiology. FNAC (Fine-needle aspiration cytology) is a useful and reliable tool for the diagnosis of RDD, and as such, biopsy is avoidable.

Antiphospholipid antibodies and systemic scleroderma.

OBJECTIVE: Antiphospholipid antibodies (APLs) could be associated with an increased risk of vascular pathologies in systemic scleroderma. The aim of our study was to search for APLs in patients affected by systemic scleroderma and to evaluate their involvement in the clinical manifestations of this disease. MATERIALS AND METHODS: We conducted a cross-sectional descriptive study, from January 2009 until August 2010, with patients received at the Department of Dermatology (Dakar, Senegal). Blood samples were taken at the hematology laboratory and were analyzed for the presence of APLs. RESULTS: Forty patients were recruited. Various types of either isolated or associated APLs were found in 23 patients, i.e. 57.5% of the study population. The most frequently encountered antibody was IgG anti-ß2 GPI (37.5% of the patients), followed by anticardiolipins (17.5%) and lupus anticoagulants (5%). No statistically significant association of positive antiphospholipid-related tests to any of the scleroderma complications could be demonstrated. CONCLUSION: A high proportion of patients showing association of systemic scleroderma and APLs suggests the presence of a morbid correlation between these 2 pathologies. It would be useful to follow a cohort of patients affected by systemic scleroderma in order to monitor vascular complications following confirmation of the presence of antiphospholipid syndrome. CONFLICT OF INTEREST: None declared.