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Objectives: To determine the prevalence of vitamin B12 deficiency in a Tunisian population with type 2 diabetes (T2D) on metformin treatment for more than three years and to identify its risk factors. Methods: This is a cross-sectional study conducted on 257 patients with T2D treated with metformin for at least three years. Patients were divided into two groups according to their vitamin B12 status. Low vitamin B12 was defined as ≤ 203 pg/mL. Results: The mean age of the patients was 59.8  ±  7.9 years. The mean duration of metformin use was 10.2  ±  5.2 years. The mean vitamin B12 level was 294.9  ±  156.4 pg/mL. The prevalence of vitamin B12 deficiency was 28.4%. Male gender, HbA1c < 7% and hyperhomocysteinemia were significantly associated with vitamin B12 deficiency (respectively p   =  0.02, p  < 0.001, p  < 0.001). Homocysteine level was negatively correlated with vitamin B12 level ( r   =  -0.2, p   =  0.001). Dose and duration of metformin treatment, peripheral neuropathy and anemia were not associated with vitamin B12 deficiency. On multivariate analysis, HbA1c < 7% and hyperhomocysteinemia were independently associated with vitamin B12 deficiency (respectively OR = 3.2, 95%CI  =  [1.6-6.3] and OR = 2.3, 95%CI  =  [1.2-4.2]). Discussion: The prevalence of vitamin B12 deficiency in patients with T2D on metformin treatment was high. Hyperhomocysteinemia is associated with vitamin B12 deficiency suggesting that the deficit occurs at the tissue level., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Platelet count is crucial for clinical decision. In cases of microcytosis, platelet count based on impedance technique (PLT-I) may overestimate platelet count., Aim: To compare PLT-I with platelet count using the optical technique (PLT-O) and establish a Mean Corpuscular Volume (MCV) threshold for considering PLT-O., Methods: A prospective analytical study conducted over two months involved blood samples collected in standard K2 EDTA tubes for complete blood count analysis, revealing microcytosis (MCV<80 fL). PLT-O analysis in channel-Ret mode was performed using the Sysmex-XN1000 (Sysmex Corporation, Kobe, Japan). Percentage of fragmented red cells (FRC%) and percentage of microcytic red cells (Micro-R%) were recorded. Blood smears stained with May-Grünwald-Giemsa were examined for potential interfering particles., Results: A strong correlation was observed between the two techniques for all platelet values as well as for PLT <150 x 109/L (correlation coefficient r = 0.971, 95% CI: [0.956-0.982]; P<10-3 and r = 0.90, 95% CI: [0.79-0.95]; P< 10-3). The Bland-Altman plot revealed a bias of 16.53 x 109/L between the two methods, with agreement limits between -55.8 and 88.8 x 109/L. A threshold MCV value indicating the use of the optical method, with a cut-off at 72.9fL, demonstrated promising performance consistent with literature findings. However, less favorable performance was observed with Micro-R%., Conclusion: Impedance could be employed in routine practice. However, for MCV<72.9 fL or in the presence of schizocytes, the hemogram validation procedure may incorporate the use of PLT-O.

Background and Objectives: Transfusion safety may be becoming dependent on the financial resources made available for transfusion structures and may vary between high-income countries (HIC) and low-to-middle-income countries (LMIC). To assess whether there is a difference in the reported TR between these two groups of countries, we examined TR reported in Tunis the capital of Tunisia, a LMIC, and compared their frequency with reported TR in HIC., Materials and Methods: Data of TR were collected from transfusion incident report (TIR) forms declared by healthcare facilities in Tunis between 2015 and 2019. They were analysed and compared to reported TR in France (ANSM) and UK (SHOT)., Results: The incidence of TR was 70.6/100 000 blood components (BP) issued. A third of TR (36.8%) occurred at night. Febrile non-hemolytic transfusion reactions (43.7%) and allergic reactions (35%) were the most reported TR respectively 22.4/100 000 BP and 17.9/100 000 BP. The rate of ABO incompatibilities was 1.96/100 000 red blood cell units (RBC): they were all caused by human error. The rates of TRALI, TACO and bacterial contaminations were respectively 1.26/100 000 BP, 1.4/100 000 RBC and 0.7/100 000 BP., Conclusion: While advanced technologies applied to transfusion have improved transfusion safety, this study shows that their impact has been relatively minor, as reported TR in LMIC are still comparable to those in HIC. ABO-incompatibilities are still higher in LMIC: this should be addressed by reinforcing the training of all healthcare personnel involved in transfusion medicine., Competing Interests: Conflict of Interest The authors have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Massive transfusion (MT) is a life-saving therapy in situations of major hemorrhage awaiting radical haemostatic treatment. Poor management and control of this therapy may, however, compromise the patient's vital prognosis. The main aim of our study was to take stock of massive transfusion practices in Tunisia. The secondary aim was to propose a massive transfusion protocol., Methods: An analytical observational study based on a questionnaire was conducted. We targeted physicians brought in their clinical practice to use MT., Results: A total of 124 clinicians responded to the questionnaire. The majority (62%) were anesthesiologists or emergency physicians. More than half of the participants were residents (51%). The use of MT based on a clinical or biological score was only found for a minority (13%). The initial order was for the majority of participants (N=69) made up of red blood cell concentrates (RBC) and fresh frozen plasma (FFP). The FFP: RBC ratio was1:2 for 51% of the participants. A higher ratio was adopted by the rest. Respectively 23.5% and 9.6% of participants transfused platelets and fibrinogen concentrates without waiting for the result of biology. The use of tranexamic acid was systematically advocated by 60.5% of clinicians. The majority (86.3%) adopted a restrictive transfusion strategy (target hemoglobin between 7 and 9 g/dl). The latter was more adopted by the youngest physicians (92.1% of residents versus 55.6% of professors; p=0.008)., Conclusions: The professional practices of MT in Tunisia are heterogeneous. Given the lack of a clear institutionalized procedure which frames this therapy, a MT protocol has thus been proposed.

Background: Multiple myeloma is a hematologic malignancy which confers a high venous thromboembolic risk. This risk is linked to patient-related factors, disease-specific mechanisms, and antimyeloma therapy, especially immunomodulatory drugs. Some studies have suggested that the thrombin generation assay may be a predictive marker of thrombosis. This study aimed to assess the hypercoagulable state in patients with multiple myeloma at diagnosis and after myeloma therapy., Methods: Thirty-one patients with multiple myeloma were included in a prospective study and were compared with 31 matched controls with age and gender. Thrombin generation assay was performed in patients at diagnosis prior to treatment initiation and at the end of myeloma therapy, and in controls. Parameters of lag time, peak thrombin concentration, time to peak, endogenous thrombin potential, and velocity index were analyzed., Results: Median age of patients at diagnosis was 58 years (11 men and 20 women). Twenty-three patients (74%) were classified as high vascular risk and received thromboprophylaxis. No thromboembolic events have been reported during follow-up, except a symptomatic pulmonary embolism in one patient which occurred at diagnosis. At baseline, patients with myeloma had significantly elevated velocity index as compared to controls (178 vs 128 nmol/L/min; P = .013). High-risk patients showed an elevation of plasma thrombin generation as compared to low-risk patients (endogenous thrombin potential = 1244 vs 1052 nmol/L/min; P = .043). Myeloma therapy did not significantly change the thrombin generation parameters., Conclusion: Thrombin generation appears to be higher in patients with myeloma compared with controls, especially in high-risk patients, and does not change significantly after treatment completion., (© 2019 John Wiley & Sons Ltd.)

Introduction and Objectives: For long, bleeding in cirrhotic patients has been associated with acquired coagulation disorders. The aim of our study was to investigate the impact of acquired coagulation disorders on bleeding risk in cirrhotic patients., Materials and Methods: Blood samples were collected from 51 cirrhotic patients with (H+) or without (H-) bleeding events and 50 controls matched by age and sex. Thrombin generation was assessed as endogenous thrombin potential (ETP). Hemostatic balance was assessed by means of ratios of pro- to anticoagulant factors and by ETP ratio with/without protein C (PC) activator (ETP ratio)., Results: Bleeding events occurred in 9 patients (17.6%). Compared with controls, VIII/anticoagulant factors, VII/PC and XII/PC were significantly higher in (H+) patients. No significant difference as regards all ratios across patient groups was detected. ETP ratio was significantly higher in (H+) patients than in controls (p=0.017). However, there was no significant difference between patient groups as regards ETP ratio., Conclusion: Hemostatic balance is shifted toward a hypercoagulability state even in cirrhotic patients who experienced bleeding. These findings provide evidence against traditional concept of hemostasis-related bleeding tendency in cirrhotic patients., (Copyright © 2019 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Despite the prolongation of coagulation tests, recent studies reported an increased frequency of thromboembolic events in patients with cirrhosis. The aim of this study was to evaluate the haemostatic balance in cirrhotic patients through assessing the variation of pro- and anticoagulant factors and evaluating the in-vitro thrombin generation in patients with cirrhosis and in healthy patients. Fifty-one cirrhotic patients with or without thromboembolic events and 50 controls matched by age and sex were enrolled. Procoagulant (factors VII, II, V, VIII, and XII) and inhibitor (protein C, protein S and antithrombin) factor activities were determined. Thrombin generation was measured as endogenous thrombin potential (ETP). Haemostatic balance was assessed by means of both procoagulant to inhibitor coagulation factor ratios and ETP with to without protein C activation ratios. There were 24 males and 27 females. The mean age was 57.8 years [16-91 years]. Pro and anticoagulant factors were significantly lower in patients than in controls (P < 0.001) except for factor VIII and protein S. In fact factor VIII level was significantly higher in patients than in controls and protein S levels were not significantly different between patients and controls. Almost all the pro to anticoagulant factor ratios were higher in cirrhotics than in controls, especially the factor VIII to protein C ratios which increased significantly from Child Pugh A to C (P < 0.001), the ratio of ETP with to without protein C activator was higher in patients than in controls, but did not reach a significant level (0.8 vs. 0.52) There was no statistically significant difference between Child classes. When comparing patients with history of thrombosis (n = 7) to those matched by age and sex and without history of thrombosis (n = 14), the ratios were not statistically different between the two groups. Haemostatic changes in cirrhosis tend to rebalance the haemostatic system. This state often results in a hypercoagulable state attested by increased pro- to anticoagulant factor ratios and a normal thrombin generation.

Background: B12 Vitamin deficiency is common in adults (20% of general population of industrialized populations), especially in elderly patients (30-40%). The etiologies of Vitamin B12 deficiency have been dominated by the cobalamin syndrome nutrient and the Biermer disease, rarely by the intake or nutritional deficiency and bad absorptions., Study Objective: Establish an etiology of vitamin B12 in a Tunisian population Methods: In a prospective study involving 100 patients with macrocytic anemia, a comprehensive assessment has been carried out of: B12 vitamin and folate intake, homocysteine, immunological assessment (antibodies, intrinsic anti-factor and anti-gastric parietal cells), an endoscopic exploration, and a dietary nutritional survey., Results: The mean age of patients was 53.6 ± 17,6 years (13 - 88 years), the gender ratio (female/male) is 1.22. The clinical symptomatology shows a functional anemia syndrome in 89% of cases, a digestive syndrome in 88% of cases, and neurological disorders in 67% of cases. The intake of B12 vitamin was reduced (<180 pg/ml) in 99 patients, associated with a hyperhomocysteinemia in 81.63% of cases.The intrinsic anti-factor antibodies were positives in 32 patients, and the antibody anti-gastric parietal cells in 85 patients. Gastric biopsy was performed in 54 patients, showing a chronic atrophic gastritis of fundic localization in 44 patients, antral in 5 patients and pan- gastric in 3 patients. The diagnosis of Biermer anemia was held in 75% of patients, that of FCS in 16% of patients, and a lack of intake in 8% of patients. The etiology was undetermined in 1% of cases., Conclusion: Vitamin B12 deficiency is common in the general population, its causes and origins are multiple, we list them in order of occurrence: Biermer disease, the FCS, and the intake deficiency in our population.

Background: BCR-ABL negative myeloproliferative neoplasms (MPN) include polycythemia Vera (PV), essential thrombocythemia (ET) and primitive myelofibrosis (PMF). the JAK2 V617F mutation has been introduced since 2008 as a major diagnostic criterion on the one hand and on the other hand, it would be linked to increased risk of thrombotic complications., Aim: This study aimed to evaluate the association of JAK2 mutation and thrombotic events in MPN., Methods: A retrospective study concerning 45 BCR-ABL negative MPN patients (mean age=53 old years, sex ratio=0.8) was conducted., Results: They were classified as PV (22 patients), ET (17 patients), PMF (3 patients) and atypical MPN (3 patients). The JAK2 mutation was found in 64.4% of patients: 72.7% of PV patients, 47% of ET patients and 66.7% of PMF patients. Thrombotic events were recorded in 11 patients (24.4%). Cerebral arteries and portal vein were the most frequent localizations. The JAK2 mutation was an independent risk factor of thrombotic events., Conclusion: Consequently, it seems that screening for JAK2 mutation in BCR-ABL negative MPN could play a role in identifying patients at high risk of vascular complications.

Background: The management of urolithiasis in patients with haemophilia poses a real challenge to the urologist., Aim: We conducted a systematic literature review to assess the safety and efficacy of extracorporeal shock wave lithotripsy (ESWL) in the treatment of urolithiasis in hemophiliacs., Methods: A systematic review was conducted by using the National Library of Medicine (PubMed) search engine between January 1985 and June 2013. We've used these key words: "haemophilia" and "extracorporeal shock wave lithotripsy". All articles dealing with the treatment of nephrolithiasis by ESWL in patients with hemophilia were included. Two independent reviewers extracted the data from each article. The data was included into a systematic review and analyzed., Results: A total of 12 medical articles were selected with a total of 25 patients. The stone size varies from 6 to 21 mm. The substitution of the deficient clotting factor started the day before the ESWL. ESWL was effective in all patients except one after 1-6 sessions / patient. An ultrasound was performed after the procedure to look for potential bleeding complications. The judgment of the substitution therapy depends on the patient's condition, the presence of hematuria and the absence of signs of bleeding. Major bleeding complications were observed in 4 patients., Conclusions: With effective substitution of deficient clotting factors, ESWL is a safe and low morbidity method in the treatment of urinary calculi in hemophiliacs.

We describe a new δ-globin variant, Hb A2-Tunis [δ46(CD5)Gly → Glu; HBD: c.140G>A]. This hemoglobin (Hb) variant displayed a faster electrophoretic mobility than normal Hb A2 and was expressed at 3.2%. The molecular defect was characterized by DNA sequencing analysis. Hb A2-Tunis was found in a carrier of a β(0)-thalassemia (β(0)-thal) [IVS I-1 (β143, G>A); HBB: c.92 + 1G>A] and Hb C [β6(A3)Glu → Lys; HBB: c.19G>A], presenting with a normal Hb A2 level. Phenotype and genotype investigations revealed that the patient has a total Hb A2 level of 7.1% that was expected for a β-thalassemia (β-thal) minor carrier.

Background: Blood transfusion is a high risk activity., Aim: To evaluate transfusion safety in planned cardiac surgery., Methods: This study was conducted in the blood bank of the Rabta Hospital in two phases: a phase to observe transfusion acts followed by corrective actions and a phase to evaluate the impacts of these corrections on the transfusion practices. Characteristics of the potentially transfused patients, the eventually prescribed, dispensed and transfused blood products and transfusion practices were studied., Results: During the observation phase, 70 patients were enrolled, 51 potentially transfused. Weaknesses concerned the mention of phenotype and transfusion history when ordering blood components as well as the double ABO/D group typing, the phenotype and the cross match performing. Final bedside controls were done in a wrong way. The distribution and the blood administration were established respectively for 208 and 232 blood products. The traceability was established for 86 blood products. During the evaluation phase, 30 patients were enrolled, 15 potentially transfused. Improvement was achieved in the transfusion history notification, phenotype and antibodies screen performing and cross matching., Conclusion: Optimisation of blood transfusion can be conceived only with collaboration between the different transfusion structures.

Background: The pathogenesis of myocardial infarction (MI) in young involves new factors including constitutional or acquired thrombophilia., Aim: To determine in patients ² 50 years, the association between coagulation factors deficiency, myocardial infarction and cardiovascular events during follow-up., Methods: Protein C (PC), PS and antithrombin (AT) were screened in 50 patients admitted for acute MI and in a healthy control group. Univariate and multivariate analysis were performed using SPSS 11.5 version., Results: PS and PC deficiency were associated to MI (respectively 24% vs 0%, p=0.001 and 14% vs 0%, p=0.016), independently for PC. No AT deficiency was detected in both groups. During followup, PS and C deficiency were predictive for venous thrombosis (p<0.05) and PS deficiency for pulmonary embolism., Conclusion: Protein C and S deficiency may play an important role in MI in young and also in thromboembolic complications during follow-up. Nevertheless, therapeutic implications remain controversial.

Background: Diabetes is one of the principal cause of blindness in adults. The aim of the study is to evaluate the frequency of ocular complications and risk factors of diabetes. It's a multicentric prospective study on a representative sample of 285 diabetics., Methods: We performed a general and an ophthalmologic exam for all patients with retinal angiography and appropriate laboratory tests. Chi 2, Fisher, Mann and Whitney tests were used as statistical methods., Results: Diabetic retinopathy was observed in 45,2% of patients, cataract in 22%, glaucoma in 5%. Diabetic retinopathy frequency rises especially with duration of diabetes and bad glycaemic control. Blindness related to diabetic retinopathy was observed in 6,25% and visual deficiency in 12,5%. The authors compared their results with literature data. They emphasize on the great value of regular better glycaemic control and other associated metabolic disorders., Conclusion: We concluded that a regular ophthalmologic follow up is necessary for early diabetic retinopathy detection and treatment.