Reticulocyte Hemoglobin-Equivalent Potentially Detects, Diagnoses and Discriminates between Stages of Iron Deficiency with High Sensitivity and Specificity.

Background: Iron deficiency anemia (IDA) is a global health problem affecting the quality of life of more than 2 billion individuals. The current practice guidelines diagnose and monitor IDA via conventional hematological and iron biomarkers, which take several months before they are corrected under an iron-treatment plan. Reticulocyte hemoglobin equivalent (Ret-He) is used as a marker in most new hematology analyzers to assess iron incorporation into erythrocyte hemoglobin directly. This study aims to examine the efficacy of Ret-He as a marker for iron deficiency (ID) and IDA and investigate whether Ret-He is sensitive to iron therapy. Methods: Two blood samples were drawn from 182 participants for CBC and iron profile measurements. Follow-up samples were drawn from participants with a confirmed diagnosis of ID and/or IDA. Results: Ret-He levels were lower in the ID and IDA groups compared to the control (p < 0.0001), and lower in the IDA group compared to the ID group (p < 0.0001). Ret-He was correlated with ferritin at ID level (<30.0 mg/mL; r = 0.39) and severe IDA (<13.0 ng/mL; p-value < 0.01, r = 0.57). Cut-off values of <28.25 pg for ID and <21.55 pg for IDA showed a higher specificity and sensitivity (ID; AUC: 0.99, sensitivity: 92.73%, specificity: 97.87%) and (IDA; AUC: 0.94, sensitivity: 90.63%, specificity: 92.31%). Finally, Ret-He successfully reflected the iron therapy (p < 0.001) when compared to hemoglobin (Hb) (p = 0.1). Conclusions: Ret-He is a potential marker for detecting and diagnosing different stages of ID with high validity and is very sensitive in reflecting the iron incorporation in a short time.

The value of transfusion of phenotyped blood units for thalassemia and sickle cell anemia patients at an academic center.

BACKGROUND: Blood transfusion is the first-line treatment for patients with thalassemia and many sickle cell patients. However, cases of unregulated blood transfusion are shown to carry a high risk of alloimmunization to red blood cells (RBCs), which can lead to a hemolytic transfusion reaction and be fatal to patients. Screening and identification of alloantibodies are, therefore, essential practice in blood transfusion services. Transfusion of phenotyped blood can minimize these risks to patients. STUDY DESIGN AND METHODS: A prospective study was carried out on 1015 donors, and a prospective and retrospective study was carried out on 208 multiple transfused patients with ß-thalassemia and sickle cell anemia. Donor and patient samples were subjected to Rh & K typing, and patient samples were also subjected to screening & identification of RBC antibodies. We aimed to determine the prevalence of RBC antigens in thalassemia and sickle cell patients, as well as blood donors, at King Abdulaziz University Hospital and the frequency of alloimmunization in the selected patients. RESULTS: The most commonly detected Rh-phenotype in donors was R1r (32.02%), followed by R1R1 (23.25%). Only 9.16% of donors were positive for the K antigen. The prevalence of Rh and K blood group antigens was also reported: the highest detected Rh-phenotype was R1r (40.86%) followed by R1R2 (24.04%) with only (6.25%) positive patients for K antigen. The rate of alloimmunization among sickle cell anemia and thalassemia patients was 39.42% and 35.57%, respectively. The highest specificity rates of the alloantibodies were recorded for anti-E and anti-K in both patient groups. CONCLUSION: The rate of alloimmunization in transfused patients was high and particularly observed against the Rh and K antigens. This study emphasizes the clinical need for typing patient RBCs prior to transfusion so as to provide phenotyped matched blood units and minimize the risks and associated morbidities of alloimmunization. Keeping a database of phenotyped blood donors is essential for the clinically effective and safe management of transfusion patients.

The influence of polymorphisms in the drug transporter, ABCB1 on the toxicity of glucocorticoids in Saudi children with acute lymphoblastic leukaemia.

BACKGROUND: Glucocorticoids play essential roles in the treatment of childhood acute lymphoblastic leukaemia (ALL); however, treatment with these agents can result in severe side-effects. This study, the first of its kind in a Saudi population, investigates associations of ABCB1 gene polymorphisms (pharmacodynamics and pharmacokinetic) with the development of toxicity and side effects (glucose abnormality, liver toxicity and infection) in a small population of Saudi children with ALL. METHODS: Three single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs 3213619 T129C, rs 2032582 G2677T and rs1045642 C3435T) were analysed in 70 Saudi children with ALL and 60 control subjects. Participants were treated according to the ALL 2000 study protocol. Toxicities were assessed and associations with genotypes were evaluated according to Common Toxicity Criteria (NCI-CTC). RESULTS: Significant associations were observed among carriers and the mutated genotype C3435T (ABCB1), which had an incidence of infection (p = 0.05). Although no correlations were found between liver toxicity and glucose abnormalities for patients carrying ABCB1 SNPs, risk factors for liver toxicity were elevated by a factor of three for patients carrying the SNP G2677T, OR 3.00 (1.034-8.702). The risk factor of glucose abnormality toxicity for the patients carring T129C were increased three times OR 3.06 (0.486-19.198). CONCLUSIONS: In terms of infection incidence, polymorphism C3435T may contribute to potential life-threatening infections during paediatric ALL therapy, through glucocorticoid usage.

Novel mutations in the displacement loop of mitochondrial DNA are associated with acute lymphoblastic leukemia: a genetic sequencing study.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. MATERIALS AND METHODS: This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA (mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of the d-loop region were amplified and successfully sequenced. RESULTS: This revealed 132 mutations at 25 positions in this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were all identified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles were observed in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loop region of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop of mtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions (19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed. CONCLUSIONS: Further investigation of the relationship between mutations in mitochondrial d-loop genes and incidence of acute lymphoblastic leukemia is recommended.