How to improve issuing, transfusion and follow-up of blood components in Southern and Eastern Mediterranean countries? A benchmark assessment.

To determine the existence of guidelines regarding the appropriate clinical use of blood and blood components, transfusion requests, and blood issuing/reception documents and procedures. The different bedside transfusion organizations/processes and hemovigilance are also analyzed. The ultimate objective is to identify safe potential options in order to improve blood safety at the lowest cost. Data emanating from eight Arabic eastern/southern Mediterranean countries who responded to five surveys were collected and tabulated. National recommendations for the clinical use of blood components especially for hemoglobinopathies are lacking in some countries. In matter of good practices in the prescription, issuing and reception of BCs, efforts were made either on national or local basis. Procedures regarding patient information and ethical issues are still lacking. Almost all Mediterranean countries apply two blood testing procedures on each patient sample. Only Morocco, Tunisia and Algeria perform bed side blood group testing; Egypt and Lebanon perform antibody screen and antiglobulin cross matching universally. Automation for blood testing is insufficiently implemented in almost all countries and electronic release is almost absent. National hemovigilance policy is implemented in Tunisia, Morocco, and Lebanon but the reporting system remains inoperative. Insufficient resources severely hinders the implementation of expensive procedures and programs; however, the present work identifies safe procedures that might save resources to improve other parts in the transfusion process (e.g. electronic release to improve safety in issuing). Moreover, setting up regulations regarding ethics in transfusing recipients along with local transfusion committees are crucially needed to implement hemovigilance in transfusion practice.

Second Tunisian case of Anti -Tja mediated recurrent abortions.

The diagnosis and the treatment of rare phenotypes remain a problematic situation in many countries especially in Tunisia. Individuals with rare phenotype may develop clinically significant red cell antibodies directed against the high incidence Antigens they lack. A 35 years old patient was referred to our laboratory to explain a high incidence (twelve) of recurrent miscarriage during the first and second terms of pregnancy. This patient was grouped as O Rhesus: 1, -2, -3, 4, 5 K:-1. In her plasma we identified a pan-reactive anti-PP1PK antibody (anti-Tja) recognized to be responsible of spontaneous recurrent abortions. The red cell phenotype was P1 and Tja negative. More investigations concluded to the absence of auto and other allo-antibodies association. Therapeutic plasmapheresis from early stages was suggested for the future pregnancy to remove anti-public antibodies in order to maintain normal placenta functions. The Anti-Tja antibody, naturally occurring in patients with rare p phenotype, has the ability to induce recurrent spontaneous miscarriages and to cause immediate hemolytic transfusion reactions. Despite the absence of compatible donors in her family, this patient is not in an impasse situation because two donors with the same phenotype were identified when investigating a first case in 2013.

Predictors of autoimmune hemolytic anemia in beta-thalassemia patients with underlying red blood cells autoantibodies.

In beta-thalassemia patients, erythrocyte autoantibodies can remain silent or lead to Autoimmune Hemolytic Anemia (AIHA).The aim of this study was to identify predictors of AIHA in beta-thalassemia patients with positive Direct Antiglobulin Test (DAT), in Tunisia. This longitudinal prognosis study was carried out on beta-thalassemia patients with a positive confirmed DAT. Predictors of AIHA were identified the Kaplan-Meier method. A Cox model analysis was used to identify independent predictors. Among 385 beta thalassemia patients, 87 developed positive DAT (22.6%). Autoimmune hemolytic anemia was occurred in 25 patients. Multivariate analysis showed that AIHA was independently associated with beta-thalassemia intermedia and similar family history of AIHA. Splenectomy in patients with positive DAT was independently associated with an increased risk of AIHA (HR = 6.175, CI: 2.049-18.612, p < 0.001). The risk of developing AIHA was higher during the first 72 transfusions. Autoimmune hemolytic anemia was significantly associated with polyspecific DAT (anti-complement and anti-IgG), blood group AB and prior alloimmunization. Whereas transfusion by phenotypic and leukoreduced blood was a protective factor. In summary, splenectomy after autoimmunization, prior alloimmunization, DAT specificity (IgG with complement), thalassemia intermedia, AB blood group and family history of AIHA were strongly associated with AIHA. Leukoreduced blood transfusion had a proven preventive role.

The role of access to affordable and quality assured blood and blood products for achieving Universal Health Coverage (Editorial).

The theme of World Health Day 2018 is 'Universal health coverage: everyone, everywhere' under the slogan 'Health for All'. Universal Health Coverage (UHC), as pertains to blood and blood products, means that all individuals and communities have access to affordable and timely supplies of safe and quality-assured blood and blood products. Blood and blood products are essential components in the proper management of women suffering from bleeding associated with pregnancy and childbirth; children suffering from severe anaemia due to malaria and malnutrition; patients with blood and bone marrow disorders and immune deficiency conditions; victims of trauma, emergencies, disasters and accidents; and patients undergoing advanced medical and surgical procedures.

Killer cell immunoglobulin-like receptor (KIR) locus profiles in the Tunisian population.

Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activatory receptors that are expressed by most natural killer (NK) cells. The KIR gene family is polymorphic: genomic diversity is achieved through differences in gene content and allelic polymorphism. The number of KIR loci has been reported to vary among individuals, resulting in different KIR haplotypes. In this study we report the genotypic structure of KIRs in 267 unrelated and healthy Tunisian subjects by polymerase chain reaction-sequence-specific primer (PCR-SSP) method. All 16 KIR genes were observed in the population with different frequencies; framework genes KIR3DP1 and KIR3DL2 and the nonframework genes KIR2DL1 and KIR2DP1 were present in all individuals. A total of 26 different KIR gene profiles and 54 subgenotypes were observed in the tested population samples. Genotype 1, with a frequency of 36.6%, is the most commonly observed in the Tunisian population. Our results showed that the Tunisian population possesses the previously reported general features of the Caucasian as well as African populations, with some additional interesting differences. Such knowledge of the KIR gene distribution in populations is very useful in the study of associations with diseases and in selection of donors for haploidentical bone marrow transplantation.

[The JAK2 mutation in myeloproliferative disorders: A predictive factor of thrombosis]. / La mutation JAK2 dans les syndromes myéloprolifératifs BCR-ABL négatifs: facteur prédictif de thrombose.

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.

Fanconi anemia: contribution of molecular analyses to the identification of bone marrow graft donors and the study of chimerism in grafted patients.

We report on the effectiveness of molecular studies regarding Fanconi anemia (FA) for a better selection of bone marrow graft donors and for post-transplant follow up. Ten unrelated FA patients and their families were analyzed by microsatellite markers. In 9 cases, the cytogenetic investigation of potential human leukocyte antigen (HLA)-identical related donors was normal, and the molecular analyses confirmed that they were also either normal or heterozygous carriers. For 1 patient, cytogenetic analysis of an HLA-identical sibling donor yielded ambiguous results with a relatively high number of chromosomal breakages using cross-linking agents. However, genotyping of this potential donor demonstrated his heterozygous state. Nine patients have received allogeneic bone marrow transplantation from HLA-matched related donors. Microsatellite analysis showed complete chimerism (CC) in all cases. The median follow up was 54 months (range 8-144 months). One patient out of 9 with CC rejected her graft without prior detection of a transitional mixed chimerism. Among these patients, 1 died 25 months after the transplantation of a chronic graft-versus-host-disease (GVHD). We conclude that, when the cytogenetic studies are not conclusive, molecular analyses are crucial to distinguish heterozygous carriers from asymptomatic FA Tunisian patients. Molecular analyses also allowed the evaluation of hematopoietic chimerism after allogeneic bone marrow transplantation and might be of value to identify patients with a high risk for graft rejection.