Microcytic Red Blood Cells Research Articles

Can New Advanced Clinical Parameters Be Used in the Diagnosis of Vitamin B12 Deficiency?

The measurement of vitamin B12 levels has low sensitivity for the diagnosis of vitamin B12 deficiency, therefore, clinicians may prefer to decide the deficiency with the patient's clinic. In this study, the diagnostic values of the classical and advanced clinical complete blood count parameters were investigated to find a new marker in the diagnosis of vitamin B12 deficiency. 150 adult volunteers were included in the study and volunteers were divided into two groups according to their vitamin B12 levels (with or without vitamin B12 deficiency) and hemoglobin levels (with or without anemia). The differences and correlations of laboratory test results between groups were examined. Equivalent of reticulocyte hemoglobin, equivalent of erythrocyte hemoglobin and delta-hemoglobin were found significant differences between groups with or without vitamin B12 deficiency. Hypo-hemoglobinised red cells and hyper-hemoglobinised red cells were found significant difference between groups with or without anemia. Significant positive correlations were found between vitamin B12 levels and equivalent of reticulocyte hemoglobin, equivalent of erythrocyte hemoglobin and delta-hemoglobin. Significant positive correlations were found between hemoglobin levels and macrocytic red blood cells, equivalent of reticulocyte hemoglobin, equivalent of erythrocyte hemoglobin, delta hemoglobin and hyper-hemoglobinised red cells; negative correlations with microcytic red blood cells and hypo-hemoglobinised red cells. It is suggested that these advanced clinical parameters of complete blood count analysis may be used to determine vitamin B12 deficiency.

Septic paravertebral abscess and inferior vena cava thrombosis complicated by uro-sepsis: Case report

Paravertebral abscess is an uncommon and potentially dangerous illness characterized by the buildup of pus in the anatomical area surrounding the spinal column. A 65-year-old female, who has diabetes and high blood pressure, came in with intense discomfort in her lower back that spreads to her lower limbs, making it difficult for her to move. She also has a high fever, excessive sweating, and has lost a large amount of weight. The blood tests indicate the following abnormalities: low Hb level of 9.6 g/dl, low MCV of 70 fl, elevated total white blood cell count of 15.8 × 109/L, elevated neutrophil count of 12.4 × 109/L, normal lymphocyte count of 2.8 × 109/L, high platelet count of 485 × 109/L, and elevated ESR of 110 mm/hr. The level of phosphatase was raised to 247 U/L, which is beyond the usual range of 40-150 U/L. The blood film reveals the presence of hypochromic microcytic red blood cells, which are indicative of iron deficiency anemia. There is also evidence of neutrophil leukocytosis in the white blood cells, with no immature cells observed. Additionally, an increase in platelets is observed in the film. The D-dimer level is 2009 ng/ml, which is within the normal range of less than 500 ng/ml. The CRP level is 48 gm/l, which is above the usual range of less than 6 gm/l. The bone marrow testing yielded normal results. The blood culture indicated the presence of Streptococcus epidermidis growth. Radiological tests revealed that a CE-MRI of the dorsal and lumbar spine indicated the presence of a para-aortic abscess together with septic thrombosis of the inferior vena cava. Paravertebral abscess is a critical emergent condition required a necessary therapy protocols to stabilize the patient status. The timing of intervention is crucial in cases of paravertebral abscess, as the existence of a mass can led to spinal cord compression.

Diagnostic Evaluation of Polycythemia Vera at High Altitude.

Polycythemia is a common medical problem, frequently acquired and reactive to secondary conditions. High-altitude-associated hypoxia contributes to the greater prevalence of polycythemia at altitude. Primary clonal polycythemia vera (PV), even though it is rare, requires a different therapeutic approach. Suspicion of PV usually drives the diagnostic workup of polycythemia. In this retrospective lab record study, we collected all JAK2 tests requested over a three-year period. We analyzed requests that were made for the evaluation of polycythemia. Complete blood count (CBC) and imaging of the abdomen were collected. Out of 208 total requests, 136 were for the purpose of polycythemia evaluation. JAK2 mutation was positive (confirming the presence of PV) in 22 (16.7%) cases. PV patients have the usual demographics reported elsewhere. Additionally, PV patients exhibit distinct hemogram results featuring leukocytosis, thrombocytosis, and hypochromic microcytic red blood cells (RBCs) related to the associated iron deficiency. Many patients with polycythemia at altitude might be unnecessarily considered for an evaluation of PV, if hemoglobin/hematocrit is the sole deciding criterion. PV patients have a distinct CBC pattern that can be exploited to better select patients with polycythemia for further evaluation and thus reduce unnecessary workups.

Survival of transfused red blood cells from a donor with alpha-thalassemia trait in a recipient with sickle cell disease.

Post-transfusion survival of donor red blood cells (RBCs) is important for effective chronic transfusion therapy in conditions including sickle cell disease (SCD). Biotin labeling RBCs allows direct in vivo measurement of multiple donor RBC units simultaneously post-transfusion. In an observational trial of patients with SCD receiving monthly chronic transfusion therapy, aliquots of RBCs from one transfusion episode were biotin-labeled and infused along with the unlabeled RBC units. Serial blood samples were obtained to measure RBC survival. Donor units were tested for RBC indices, hemoglobin fractionation, and glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. For microcytic donor RBCs (MCV < 70 fL), HBA1 and HBA2 genetic testing was performed on whole blood. We present one recipient, a pediatric patient with SCD and splenectomy who received two RBC units with aliquots from each unit labeled at distinct biotin densities (2 and 18 μg/mL biotin). One donor unit was identified to have microcytosis (MCV 68.5 fL after biotinylation); whole blood sample obtained at a subsequent donation showed 2-gene deletion alpha-thalassemia trait (ɑ-3.7kb/ɑ-3.7kb) and normal serum ferritin. G6PD activity was >60% of normal mean for both. The RBCs with alpha-thalassemia RBC had accelerated clearance and increased surface phosphatidylserine post-transfusion, as compared with the normocytic RBC (half life 65 vs. 86 days, respectively). Post-transfusion RBC survival may be lower for units from donors with alpha-thalassemia trait, although the impact of thalassemia trait donors on transfusion efficacy requires further study.

Diagnostic performance of automated red cell parameters in predicting bone marrow iron stores.

The aim of the study was to determine the diagnostic performance of novel automated red cell parameters for estimating bone marrow iron stores. The study was a retrospective single-centre study based on data from an automated haematology analyser and results of bone marrow iron staining. Red cell parameters were measured on a Sysmex XN-series haematology analyser. Bone marrow iron stores were assessed semiquantitatively bycytochemical reaction according to Perls. The analysis included 429 bone marrow aspirate smears from 393 patients. Median age of patients was 67 years, 52 % of them were female. The most common indication for bone marrow examination was a plasma cell dyscrasia (n=104; 24 %). Median values of percentage of hypochromic and hyperchromic red blood cells (%HYPO-He, %HYPER-He), reticulocyte haemoglobin equivalent (RET-He) and microcytic red blood cells (MicroR) were statistically significantly different between cases with iron deplete and iron replete bone marrow. In a logistic regression model, ferritin was the best predictor of bone marrow iron stores (AUC=0.891), outperforming RET-He and %HYPER-He (AUC=0.736 and AUC=0.722, respectively). In a combined model, ferritin/MicroR index achieved the highest diagnostic accuracy (AUC=0.915), outperforming sTfR/log ferritin index (AUC=0.855). While single automated red cell parameters did not show improved diagnostic accuracy when compared to traditional iron biomarkers, a novel index ferritin/MicroR has the potential to outperform ferritin and sTfR/log ferritin index for predicting bone marrow iron stores. Further research is needed for interpretation and implementation of novel parameters and indices, especially in the context of unexplained anaemia and myelodysplastic syndromes.

ESTIMATION AND COMPARISON OF PLATELET COUNT: AUTOMATED ANALYZERVS MANUAL PERIPHERAL SMEAR METHOD

Accurately assessing platelet counts holds paramount importance in the realm of diagnostics and treatment. The adoption of automated methods within the diagnostic landscape is steadily growing, attributed to their multifaceted benefits. Nonetheless, automated analyzers sometimes yield erroneous results, particularly in scenarios involving particles of comparable sizes or instances of light scattering. These encompass fragmented red blood cells (RBCs), microcytic RBCs, and the presence of oversized platelets or platelet clusters. In response, the manual estimation of platelet counts using Leishmans stain validation gains significance. Method: this study encompassed the collection of blood samples from a diverse pool of 100 patients, including both inpatients and outpatients, spanning the period from 1st February 2023 to 31st July 2023. These samples, procured from GMC Doda and its affiliated hospital, were collected in ethylenediaminetetraacetic acid (EDTA) tubes. The manual platelet count was done, followed by a comprehensive comparative analysis with the counts obtained through automated platelet analysis. Results: the outcomes unveiled a nuanced trend, with manual slide-derived results slightly surpassing those generated by automated analyzers. Conclusion: This study concluded a discernible correlation between automated and manual methodologies for platelet count assessment. Nevertheless, in instances marked by exceedingly high or low platelet counts, the manual method holds its ground, ensuring precision by circumventing concerns like platelet clumping or uneven distribution.

Revisiting and updating molecular epidemiology of α-thalassemia mutations in Thailand using MLPA and new multiplex gap-PCR for nine α-thalassemia deletion

α-thalassemia is an inherited blood disorder that is most frequently found in Southeast Asian populations. In Thailand, molecular characterization can diagnose most patients with α-thalassemia; however, several atypical patients are also observed in routine analyses. Here, we characterized α-thalassemia mutations among 137 Hemoglobin H (Hb H) disease patients and three fetuses of Hb Bart’s hydrops, a fatal clinical phenotype of α-thalassemia. Specifically, we performed multiplex ligation-dependent probe amplification (MLPA) followed by direct DNA sequencing. We noticed common genotypes in 129 patients and eight patients had rare Hb H disease caused by compound heterozygous α0-thalassemia (--CR or --SA deletion) with α+-thalassemia (-α3.7/-α4.2/αConstant Springα). Furthermore, two affected fetuses had the --SA/--SEA and one had the --CR/--SEA genotypes. Next, we developed and validated a new multiplex gap-PCR and applied this method to 844 subjects with microcytic red blood cells (RBCs) from various parts of Thailand. The frequency of heterozygous α0-thalassemia was dominated by --SEA 363/844 (43%), followed by --THAI 3/844 (0.4%), --SA 2/844 (0.2%), and --CR 2/844 (0.2%) mutations. These findings suggest that aforementioned four mutations should be routinely applied to increase the effectiveness of diagnosis and genetic counseling in this region.

Iron Deficiency Anaemia: The Psychological Menace.

Madam, As per the World Health Organisation, anaemia is the condition of having an inadequate number of red blood cells or if the concentration of haemoglobin in them is reduced. Haemoglobin is a complex protein component of RBCs that carries oxygen around the body, a deficiency that can lead the person to experience fatigue, dyspnoea, weakness, dizziness etc.1 Such an ailment is bound to make daily life activities difficult and take a toll on one’s mental health. The WHO approximates that anaemia is prevalent in two billion people world-wide. There are many reasons for anaemia, including nutritional deficiencies, menstruation, stomach ulcers, parasitic infections, chronic illnesses and haemoglobinopathies etc. Nutritional deficits are the most common cause of anaemia, among which iron deficiency is namely the guiltiest, accounting for half of the total cases world-wide. It is a global public health travesty, especially for children and pregnant women.1 A vital component in the synthesis of the haemoglobin molecule is iron. Haemoglobin that is iron-deprived produces hypochromic and microcytic red blood cells. Iron is associated with several neurological functions, a deficiency of which leads to poor myelination of the white matter as well as a disturbance in monoamine metabolism. Additionally, fluctuations in the levels of brain iron interfere with the homeostasis of neurotransmitters such as gamma-aminobutyric acid and glutamate. Enzymes for synthesising neurotransmitters like dopamine and serotonin- essential in the modification of mood, anxiety, and other emotional behaviours- require iron as a vital component.2 Abnormalities in the physiology of these neurochemicals due to disruptions in an adequate iron supply will undoubtedly increase the likelihood of associated disorders, including but not limited to depression, anxiety, sleeping issues, developmental and emotional afflictions etc. A research paper comparing the risk of various psychiatric illnesses in patients with iron deficiency anaemia and healthy controls concluded the IDA group at a higher risk for developing anxiety, depression, sleep disruption, and psychotic disorders. Interestingly, it also found t that IDA with iron supplementation reported remarkably lower risks of psychiatric disturbances.3 It is, thus, necessary to monitor iron levels in anaemic individuals and where needed, introduce supplements to reduce the risk of developing and/or progression of psychiatric disorders. Further studies are also required to better expound on the relationship between iron deficiency anaemia and psychiatric illnesses.

A study to assess the Effectiveness of Structured Teaching Program on knowledge regarding Iron Deficiency Anemia among Adolescent girls of Swami Dayananda Saraswati Inter College at Ayodhya, Uttar Pradesh

Abstract: Introduction-Iron is an important micronutrient which is Very Important for various functions in human body. It is essential for cellular growth and differentiation, oxygen binding, transport and storage, enzymatic reactions, immune function, cognitive function, mental and physical growth etc. So, deficiency of iron due to either physiological or pathological reason can affect mental and physical growth resulting in decreased learning capacity and work productivity. Iron Deficiency Anemia is characterized by a defect in haemoglobin synthesis, resulting in hypochromic and microcytic red blood cells. Iron deficiency can result either due to less nutritional supply, increased demand or blood loss due to any reason. Anemia is a serious global public health problem that particularly affects young children, Adolescent and pregnant women. Although IDA occurs at all ages and involves both sexes, adolescent girls are more prone to it. The World Health Organization (WHO) defined adolescents as the population of 10-19 years of age.

Development of molecular diagnostic platform for α0 -thalassemia 44.6kb (Chiang Rai, --CR ) deletion in individuals with microcytic red blood cells across Thailand.

The α0 -thalassemia 44.6kb or Chiang Rai (--CR ) deletion has been reported in northern Thailand and is capable of causing hemoglobin (Hb) H disease and a lethal α-thalassemia genotype, Hb Bart's hydrops fetalis, in this region. However, there are no current data regarding the frequency of --CR nationwide due to a lack of effective diagnostic assay. Therefore, this study aimed to develop a reliable platform for simultaneous genotyping of--CR and two common α0 -thalassemias in Thailand (--SEA and --THAI ) and investigate the frequency of--CR across Thailand. Multiplex gap-PCR assay and five renewable plasmid DNA controls for--CR ,--SEA , --THAI , α2-globin (HBA2), and β-actin (ACTB) were newly developed and validated with reference methods. The developed assay was further tested on 1046 unrelated individuals with a reduced mean corpuscular volume (MCV) of less than 75 fl for investigating genotypic and allelic spectrum of --CR . Our developed assay showed 100% concordance with reference methods. The results were valid and reproducible throughout hundreds of reactions. Comparison of the genotypic and allelic spectra revealed that heterozygous --SEA (--SEA /αα) and --SEA alleles were dominant with the frequency of 22.85% (239/1046) and 13.34% (279/2092), respectively. Of these, --THAI and --CR were relatively rare in this population and comparable to each other with the allelic frequency of 0.14% (3/2092). This study successfully established a reliable molecular diagnostic platform for genotyping of --CR , --SEA , and --THAI in a single reaction. Additionally, we demonstrated the frequency of --CR in Thailand for the first time and provided knowledge basis for the planning of severe α-thalassemia prevention and control programs in Thailand, where thalassemia is endemic.

Morphological Changes in Red Blood Cells, White Blood Cells, and Platelets in COVID-19 Infected Patients: A Cross-sectional Study

Introduction: Coronavirus Disease-2019 (COVID-19) is a highly infectious virus that mutates rapidly. This has led to the emergence of newer variants that can spread more easily and may be more resistant to current treatments and vaccines. It is possible that new variants could emerge in the future that could be even more dangerous than the current ones. Aim: To identify and describe characteristic changes in peripheral smears of COVID-19 patients. Materials and Methods: A cross-sectional study was conducted at Government Medical Hospital Nizamabad, Telangana, India from March 20, 2021, to June 10, 2021. A total of 600 COVID-19 patients who were tested positive via Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) were included, and blood tests were performed on the day of admission before any prior intervention. Samples were analysed using a Complete Blood Count (CBC) analyser, and peripheral smears were examined to identify the morphological changes of Red Blood Cells (RBCs), White Blood Cells (WBCs), and Platelets in COVID-19-affected patients. These changes help assess the disease process, its severity, and aid in its proper management. Results: Out of the 600 cases, 384 (64%) were males, and 216 (36%) were females. The study showed the following RBC changes: microcytic hypochromic RBCs 333 (55.5%), macrocytic RBCs 66 (11%), dimorphic picture 33 (5.5%); WBCs showed neutrophilia 535 (89.17%), lymphopenia 535 (89.17%), pseudo Pelger-Huët cells 468 (78%), smudge cells 360 (60%), reactive lymphocytes 360 (60%), large granular lymphocytes 72 (12%), and large giant platelets 444 (74%) in peripheral smears of COVID-19 patients. Conclusion: As COVID-19 patients showed specific morphological changes in RBCs, WBCs, and Platelets, CBC and peripheral smear analysis can be interpreted in conjunction with other clinical and confirmatory tests for prognostication and management of COVID-19 patients.

Altered Cellular Sedimentation during Apheresis Impacts Outcomes of Peripheral Blood Stem Cell Collection Efficiency in Patients with Sickle Cell Disease

Recent reports have demonstrated the potential for gene therapy as a therapeutic option to achieve a durable cure in patients with sickle cell disease (SCD). However, for these emerging cell therapies, relatively large numbers of peripheral blood hematopoietic stem cells (PB HSCs) are required to generate a therapeutic dose. Outcomes of stem cell collections in patients with SCD are highly variable, at times yielding far fewer numbers of HSCs in the product than predicted by the number of PB CD34+ cells. While the CXCR4 antagonist plerixafor has emerged as a safe and reliable drug to mobilize CD34+ cells in patients with SCD, collection failures continue to occur requiring additional cycles or failure to generate a gene therapy product. We sought to understand the mechanics affecting stem cell sedimentation in real time and posited that SCD disease associated changes to red cells results in altered HSC sedimentation during apheresis, negatively impacting collection. Methods Autologous PB stem cell collections were performed in patients with SCD following mobilization with 240ug/kg plerixafor. To uncover the mechanisms impacting apheresis efficiency for collecting PB HSCs, we devised a method to interrogate the sedimentation of cells in peripheral blood in real time, by interrupting the return collection circuit line. Cellular composition analyses of the collecting interfaces were performed including CD34+ enumeration by flow cytometry, CBC and differential, reticulocyte counts, and surface CD47 expression of red blood cells (RBCs). Results Patients were mobilized with 240ug/kg of plerixafor up to 6 hours before apheresis collection. We collected fewer cells than predicted (3.78 million cells/kg) in these patients with an overall average apheresis collection efficiency of 38%, and a strikingly wide range of 2%-107%. We determined that the lower collection efficiency outcomes were primarily derived when using standard apheresis interface settings. The pre-apheresis PB CD34+ counts were less predictive of total CD34+ cells collected (p=0.012) in patients with SCD (r2=0.2557, p=0.0023) when compared to historical control patients without SCD (r2=0.7638, p<0.0001). Real time measurement of cell counts at standard (Hematocrit 3%, S) and deep (Hematocrit 5%, D) collecting interfaces of the apheresis machine showed a significant decrease in lymphocytes (p=0.0146), increase in monocytes (p=0.0496), and increase enrichment in CD34+ cells at the D interface (Panel A). Enrichment of CD34+ cells correlated with monocyte enrichment and (n=21, r2=0.6706, p<0.0001) and an increased fold change in CD34+ cells between the S and D interfaces correlated with higher PB reticulocyte percentage (r2=0.5295, p=0.0111). Further analysis of the individual collection interfaces revealed that most RBCs were HbS containing despite a PB HbS concentration <30%, consistent with an enrichment for shorter lived sickle red cells. CD47 expression has been previously reported in higher concentrations on the surface of younger RBCs during erythropoiesis. Surface expression of CD47 was found to be significantly higher at both the S and D interfaces compared to the PB of patients, indicating that the accumulation of a younger population of RBCs at the collecting interfaces. As microcytic RBCs have been associated with poor collection efficiencies, the SCD red cell hemoglobin concentration in the PB was used as a marker for size and a significant correlation was determined (r2=0.6086, p=0.0001). Patients with SCD can mobilize PB HSC in response to plerixafor but demonstrate specific characteristics that impede the collection of stem cells. During apheresis, CD34+ stem cells sediment at a deeper hematocrit interface in the buffy coat as a result of displacement by the younger patient-derived population of RBCs. The relative shift in erythrocyte sedimentation requires a corresponding alteration in collection strategies to improve the collection efficiency. In addition to red cell age, other factors that affect red cell buoyancy including iron status or additional globin gene mutations negatively impact apheresis stem cell collections. Full assessment of red cell parameters can identify patients that are at risk for poor stem cell collection outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Association of Heterozygous β-Thalassemia and β-Spectrin Mutations May Result in a Phenotype of Severe Anemia

Background: The association of mutations in genes related to hereditary anemias (HA) can affect disease phenotype and severity. Understanding HA genetic basis is crucial for avoiding misdiagnosis and for adequate clinical management. β-thalassemias (BT) are characterized by a reduction of β-globulin production caused mainly by point mutations within the HBB gene or its bordering sequences. The imbalance between α and β globin production results in ineffective erythropoiesis and hemolysis. Hereditary spherocytosis (HS) is characterized by abnormalities of erythrocyte membrane proteins, resulting in spheroidal, osmotically fragile erythrocytes with varying degrees of hemolysis and anemia. HS related to spectrin deficiency is clinically heterogeneous, ranging from well-compensated hemolysis to severe anemia. Here we describe two unrelated cases in which patients had a chronic severe hypochromic microcytic hemolytic anemia with elevated HbA2 clinically compatible with BT Intermedia or Major. However, conventional β-globin gene sequencing revealed only BT trait that did not justify the clinical presentation. The extensive research for deletions or other mutations for BT were negative. We then proceeded with additional genetic investigation through exome sequencing. Aims: To investigate additional mutations related to HA that may contribute to a phenotype of severe anemia in patients with a β -Thalassemia trait. Methods: Patients' clinical features and laboratory results were collected by medical charts evaluation. The Institutional Review Board approved this research and patients signed written informed consent. β-globin gene sequencing was initially performed by conventional Sanger sequencing. Exome sequencing was performed utilizing the Illumina HiSeq2500 platform. Results: Patient 1 had a clinical picture of eventual transfusion dependence, moderate hepatic iron overload and splenomegaly. Peripheral blood smears showed hypochromic microcytic red blood cells, together with spherocytes and circulating erythroblasts. Her father was asymptomatic, with a mild hypochromic microcytic hyperproliferative anemia, and her mother had normal hemoglobin and reticulocyte counts. Patient 2 had a clinical presentation of transfusion dependence, extramedullary paravertebral hematopoiesis, moderate hepatic iron overload, mild pulmonary hypertension and leg ulcers. Peripheral blood smears showed hypochromic microcytic red blood cells, together with a moderate number of spherocytes and circulating erythroblasts; clinical and laboratory data from her relatives were not available. Laboratory workup is shown in Table 1. Exome sequencing was performed and, beyond the previously known β-globin mutations, mutations in spectrin gene were found in patient 1 (SPTB p.Leu880Gln) and patient 2 (SPTB p.Asp536Asn). The father of the Patient 1 was diagnosed with a heterozygous mutation in HBB gene, while her mother was diagnosed with a heterozygous SPTB p.Leu880Gln mutation, which did not result in anemia nor in significant hemolysis. Both spectrin mutations were already described in the literature: SPTB p.Leu880Gln was reported in association with a mutation in SPTA1 gene, resulting in a moderate anemia, while SPTB p.Asp536Asn mutation was described in an non-anemic individual. Conclusion: Our results indicate that the association of heterozygous BT and spectrin mutations may result in a phenotype of moderate to severe anemia. These data show that, in unusual severe cases of presumed BT trait, mutations responsible for HS should be investigated. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effects of iron supplementation on microcytic and hypochromic red blood cells during the third trimester of pregnancy.

Mild anaemia often occurs in the third trimester of pregnancy. Particularly in the Hb range between 101-110 g/L it is difficult to determine whether the decreased haemoglobin concentration is physiological or pathological and whether supplementation is required. The aim of this study was to gain insight into the added value of measuring the percentages of microcytic RBCs (%MicroR) and hypochromic RBCs (%Hypo-He) for monitoring effects of iron supplementation in case of suspected iron-deficient erythropoiesis (IDE) in the third trimester of pregnancy. After assessing haematological parameters and zinc protoporphyrin/heme ratio as marker for IDE, subjects were classified into a group with symptoms of IDE (n=39) or without IDE (n=106). The subjects with IDE (n=39) were treated with iron supplementation. After 4 weeks effects of treatment were evaluated. In the group of pregnant women with IDE results of %MicroR and %Hypo-He were increased (p=<.001), compared to the group without haematological symptoms of IDE, whereas RET-He, RBC-He and delta-He were decreased (p=<.001). A significant positive correlation to increased values of %MicroR (r=.75, p=<.001) and %Hypo-He (r=.77, p=<.001) with ZPP was established. However, in the ZPP interval 75-100 μmol/mol heme a slight overlap was demonstrated between subjects with and without symptoms of IDE. After iron supplementation, %Hypo-He decreased (p=.002) while %MicroR remained stable. RET-He, delta-He and RDW-SD increased (p=<.001). The added value of %MicroR and %Hypo-He as a single marker for IDE is poor. However, combined interpretation of %MicroR, %Hypo-He, Ret-He and delta-He has added value in monitoring erythropoiesis during pregnancy.

The oral ferroportin inhibitor vamifeport improves hemodynamics in a mouse model of sickle cell disease

AbstractSickle cell disease (SCD) is an inherited hemolytic anemia caused by a single point mutation in the β-globin gene of hemoglobin that leads to synthesis of sickle hemoglobin (HbS) in red blood cells (RBCs). HbS polymerizes in hypoxic conditions, leading to intravascular hemolysis, release of free hemoglobin and heme, and increased adhesion of blood cells to the endothelial vasculature, which causes painful vaso-occlusion and organ damage. HbS polymerization kinetics are strongly dependent on the intracellular HbS concentration; a relatively small reduction in cellular HbS concentration may prevent HbS polymerization and its sequelae. We hypothesized that iron restriction via blocking ferroportin, the unique iron transporter in mammals, might reduce HbS concentration in RBCs, thereby decreasing hemolysis, improving blood flow, and preventing vaso-occlusive events. Indeed, vamifeport (also known as VIT-2763), a clinical-stage oral ferroportin inhibitor, reduced hemolysis markers in the Townes model of SCD. The RBC indices of vamifeport-treated male and female Townes mice exhibited changes attributable to iron-restricted erythropoiesis: decreased corpuscular hemoglobin concentration mean and mean corpuscular volume, as well as increased hypochromic and microcytic RBC fractions. Furthermore, vamifeport reduced plasma soluble VCAM-1 concentrations, which suggests lowered vascular inflammation. Accordingly, intravital video microscopy of fluorescently labeled blood cells in the microvasculature of Townes mice treated with vamifeport revealed diminished adhesion to the endothelium and improved hemodynamics. These preclinical data provide a strong proof-of-concept for vamifeport in the Townes model of SCD and support further development of this compound as a potential novel therapy in SCD.

SEVERE IRON DEFICIENCY ANEMIA CAUSING PERICARDIAL EFFUSION

TOPIC: Signs and Symptoms of Chest Diseases TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pericardial effusions are caused by numerous etiologies including metabolic, cardiac disease, infection, neoplastic, or idiopathic. They may be isolated or part of a systemic illness. Severe iron deficiency anemia causing pericardial effusion has been rarely reported and is not well studied1. CASE PRESENTATION: A 48-year-old female without significant past medical history presented with shortness of breath and exercise intolerance. She reported a five-month history of menometrorrhagia with blood clots. Physical examination was significant for a grade 3 systolic murmur and pitting edema to the knees. Labs revealed a hemoglobin of 1.7 g/dL, hematocrit of 6.3%, MCV of 51, RDW of 34.2, and reticulocyte count of 0.0245. Hemolysis markers were negative. She was transfused four units of packed red blood cells. Iron studies were not collected prior to administration of the blood transfusions, and therefore, iron studies were not available for review. However, peripheral smear demonstrated hypochromic and microcytic red blood cells with anisocytosis, poikilocytosis, and cigar cells which are diagnostic of iron deficiency anemia. She received 1 g IV Dextran for her presumed iron deficiency anemia. Echocardiogram revealed a moderate-large circumferential pericardial effusion anterior and posterior to the heart without evidence of tamponade. The location of the effusion and her anemia precluded pericardiocentesis. Other rheumatologic and cardiac workup was negative. Her symptoms improved and she was transitioned to oral iron supplementation with a hemoglobin at discharge of 6.6 g/dL.Within three weeks of iron infusion, her hemoglobin normalized to 12.3 g/dL. A repeat echocardiogram three months after her presentation showed a small posterior pericardial effusion, markedly reduced from prior. During this period, she was readmitted for new onset status epilepticus, thought to be due to CNS vasculitis. DISCUSSION: In this patient, her subsequent hospitalization for seizures was highly suspicious for CNS vasculitis based on her imaging, presentation, and overall response to steroids. Brain biopsy however was negative for vasculitis. While it is possible that her pericardial effusion was related to an underlying autoimmune disorder, her initial rheumatologic work up was negative, and her pericardial effusions did resolve with treatment of her iron deficiency anemia. Iron deficiency anemia is an unlikely cause for pericardial effusion, and overall literature remains sparse with only two case reports documented2. CONCLUSIONS: Iron deficiency anemia has been associated with high output heart failure, and subsequent pulmonary arterial hypertension, which may cause pericardial effusions3. The differential diagnosis for pericardial effusion is extensive and should be considered in each clinical context with every patient. REFERENCE #1: Adler Y, Charron P, Imazio M, Badano L, Baron-Esqivias G, Bogaert J, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC). European Heart Journal 2015;36(42):2921-2964. REFERENCE #2: Lakhotia M, Singh J, Pahadia H, Kumar H, Sanghvi S. Pericardial effusion in severe iron deficiency anemia. Heart India 2014;2(3):88-90. REFERENCE #3: Rhodes CJ, Wharton J, Howard L, Gibbs JSR, Vonk-Noordegraaf AV, Wilkins MR. Iron deficiency in pulmonary arterial hypertension: a potential therapeutic target. European Respiratory Journal 2011;38(6):1453-1460. DISCLOSURES: No relevant relationships by Anita Fei, source=Web Response No relevant relationships by Desire Guthier, source=Web Response No relevant relationships by Alisha Hossain, source=Web Response No relevant relationships by Bradley Lash, source=Web Response No relevant relationships by Emily Skutnik, source=Web Response No relevant relationships by Andrew Viscusi, source=Web Response No relevant relationships by Ali Yazdanyar, source=Web Response

Clinical utility of Abbott Alinity hq extended red blood cell parameters in differentiating β-thalassemia trait and iron deficiency anemia.

The objective of the study was to evaluate the performance of the Abbott Alinity hq advanced multi angle polarized scatter separation (MAPSSTM )-based optical RBC technology, for the differentiation between iron deficiency anemia (IDA) and β-thalassemia carrier status. Four hundred and sixty-four samples were analyzed. 228 were healthy controls, 30 were β-thalassemia carriers, and 40 were IDA. Receiver operating characteristics analysis evaluated the performance of red cell parameters and mathematical formulas. RBC concentration was the most efficient discriminant (area under the curve; AUC of 0.963, Youden Index of 0.88) followed by red blood cell distribution width in size distribution (AUC of 0.960 and YI of 0.86), and red blood cell distribution width coefficient of variation (AUC of 0.924, and YI of 0.74). The absolute reticulocyte concentration showed good diagnostic efficiency, with AUC of 0.808. Hemoglobin distribution width, the %CV of directly measured cellular hemoglobin concentration, and CHCr, the average hemoglobin concentration of reticulocytes have emerged as novel discriminating parameters, with AUC of 0.749 and 0.785, respectively. The England and Fraser index was the best discriminating mathematical formula based on Youden Index of 0.91. The Ricerca, red blood cell distribution width index, Green and King, and Mentzner Index formulas also showed strong discriminative power. The Shine and Lal index, together with the recent mathematical formula M/H, (ratio of percent microcytic and hypochromic red blood cells) demonstrated moderate performance with AUC of 0.796 and 0.740, respectively. Extended red cell analysis delivered by the advanced optical technology on the Alinity hq hematology analyzer has efficient diagnostic utility in the initial discrimination of the two most common microcytic anemias: IDA and β-thalassemia trait.

Mendelian inheritance of anemia due to disturbed iron homeostasis

Genetic disorders that affect proteins involved in maintaining iron balance may lead to Mendelian anemias. They may be classified as defects of intestinal iron absorption, iron transport in the circulation, iron uptake and utilization by maturing erythroid cells, iron recycling by macrophages and systemic regulation of iron homeostasis. All these Mendelian anemias are rare disorders, prevalently recessive, characterized by microcytic and hypochromic red blood cells. Advances in our knowledge of iron metabolism and its systemic regulation on one side have facilitated the identification of novel iron related anemias, while on the other the study of the affected patients and of the corresponding animal models have contributed to our understanding of iron trafficking and regulation.

Analysis of haemolytic anemia's clinicohematological profile in tertiary care hospital

Introduction: The destruction of the red cell membrane causes hemolytic anemia, which can be affected by a variety of underlying pathologies. Membrane mutations, enzyme defects, hemoglobinopathies, immune destruction, and non-immune destruction are also possible causes. Hemolytic anemia can be easily diagnosed using specific laboratory procedures. Aims and Objectives: The aim of this research was to look at the clinicopathological profile of hemolytic anemia in a tertiary care hospital. Materials and Methods: A total of 70 cases were collected in a pathology department in south India. The research covered all recently diagnosed patients as well as old cases that had been followed up on. Results: Beta thalassemia trait was found to be the most common, with 40% of people having it, followed by sickle cell anemia (20%), malaria (14%), beta thalassemia major (11%), beta thalassemia intermedia (4.3%), sickle beta thalassemia (2.8%), sickle cell trait (1.4%), autoimmune hemolytic anemia (1.4%), and G6PD deficiency (1.4%). Hereditary spherocytosis and HbD Punjab both had one case. The analysis found a male preponderance. Microcytic hypochromic red blood cells with varying degrees of poikilocytosis and anisocytosis were the most common peripheral smear findings. Jaundice is the most frequent clinical manifestation, accompanied by splenomegaly, hepatomegaly, thalassemic facies, gall stones, hemolytic facies, growth retardation, and edema, Conclusion: In hemolytic anemia, hemoglobin electrophoresis is still the method of use. Hemoglobinopathies cause significant health issues in the Indian population, resulting in high morbidity and mortality. It's important to stress the importance of diagnosing hemolytic anemia so that a clear course of action can be devised for diagnostic, prevention, and treatment interventions to avoid severe complications.

The prevalence of anemia among the tribal children from the western districts of West Bengal, India

Background: Tribal population in West Bengal constitutes a significant proportion (5.1%) and the vulnerable group because of lower socio-economic status, poor literacy rate and malnutrition. The present study was conducted to evaluate hemoglobin level and prevalence of anemia among the tribal children from the western districts of West Bengal, India.Methods: A cross-sectional study was conducted on school going (class I to class VIII) tribal children (≥5 to &lt;13years) during March 2019 to February 2020. A complete blood count was done by automated blood cell counter and anemia was classified as per WHO criteria. They were also tested for markers of common nutritional anemias (serum ferritin, serum vitamin B12 and serum folate). Data entry and analysis was done on SPSS version 15. A p-value of &lt;0.05 was considered statistically significant.Results: Total 1, 010 tribal children were included with male:female=1:1.35. Among these, 46.34% (n=468) children had anemia. Among all anemic children 47.65% (n=223), 51.93% (n=243/468) and 0.42% (n=2) respectively had mild, moderate and severe anemia. There was a high prevalence (81.68%) of microcytic red blood cells in the total cohort; among anemic children, 53.94% have microcytosis while no macrocytosis was revealed. Among all grade anemias, iron, folate and vitamin B12 deficiency were found in 44.65% (n=209/468), 13.24% (n=62/468) and 25% (n=117/468) respectively.Conclusions: The prevalence of anemia among tribal children of West Bengal is a matter of concern. The high prevalence of microcytic indices in non-anemic population highlights the dire need for screening for the causes of anemia in this population.