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

INTRODUCTION: The α0 -thalassemia 44.6 kb 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. METHODS: Multiplex gap-PCR assay and five renewable plasmid DNA controls for --CR , --SEA , --THAI , α2-globin (HBA2), and ß-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 . RESULTS: 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). CONCLUSION: 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.

Clinical characteristics of blue rubber bleb nevus syndrome in adults: systematic scoping review.

BACKGROUND: Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic vascular anomaly mainly affecting the skin, central nervous system and gastrointestinal tracts. Its clinical presentation and characteristics in adult patients are unclear. AIM: To clarify the characteristics of BRBNS in adult patients with a focus on gastrointestinal symptoms. METHODS: Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including 'Blue rubber bleb nevus syndrome' from their inception to 28 December 2021. RESULTS: Ninety-nine articles, including 3 observational studies and 101 cases from case reports and series, were included. Observational studies were consistently with small sample sizes, and there was only one prospective study to show the effectiveness of sirolimus in BRBNS. Common clinical presentations included anemia (50.5%) and melena (26.5%). While skin findings were known to be representative of BRBNS, only 57.4% had known vascular malformation. The diagnosis was primarily made clinically, with only 1% being diagnosed with BRBNS through genetic sequencing. Distribution of BRBNS-related lesions were variable, but predominantly oral (55.9%), followed by small bowel (49.5%), colorectal (35.6%) and stomach (26.7%) vascular malformations. CONCLUSION: While it has been underrecognized, adult BRBNS could be a culprit for refractory microcytic anemia or occult gastrointestinal bleeding. Further studies are critical to establish a uniform understanding of diagnosis and treatment for those with adult BRBNS. The utility of genetic testing in adult BRBNS diagnosis and the patient characteristics that may benefit from sirolimus, a potentially curative agent, remain to be clarified.

Aceruloplasminemia presenting with microcytic anemia in a Turkish boy due to a novel pathogenic variant.

Aceruloplasminemia inherited autosomal recessively in the ceruloplasmin gene is a progressive disease with iron accumulation in various organs such as the brain, liver, pancreas, and retina. Ceruloplasmin gene encodes ceruloplasmin protein, which has ferroxidase activity and is involved in copper and iron metabolism. Progressive neurotoxicity, retinopathy, and diabetes may develop in about 40-60 decades. In addition, microcytic anemia accompanied by high ferritin and low ceruloplasmin level that develop at earlier ages can be first manifestation. Iron chelation may be utilized in the treatment to reduce the toxicity. Early diagnosis and treatment may delay the onset of symptoms. A 14-year-old male patient was followed up with microcytic anemia since an eight-years old. Anemia was accompanied by microcytosis, high ferritin, and low copper and ceruloplasmin levels. A novel homozygous c.690delG variant was detected in ceruloplasmin by whole exome sequencing. Clinical, laboratory and imaging findings of the patient demonstrated aceruloplasminemia. We present a boy with persistent microcytic anemia of the first manifestation at the age of eight, as the youngest case of aceruloplasminemia in the literature. Thereby, aceruloplasminemia should be kept in mind in the etiology of microcytic anemia whose cause couldn't found in childhood.

New Cases of Hypochromic Microcytic Anemia Due to Mutations in the SLC11A2 Gene and Functional Characterization of the G75R Mutation.

Divalent metal-iron transporter 1 (DMT1) is a mammalian iron transporter encoded by the SLC11A2 gene. DMT1 has a vital role in iron homeostasis by mediating iron uptake in the intestine and kidneys and by recovering iron from recycling endosomes after transferrin endocytosis. Mutations in SLC11A2 cause an ultra-rare hypochromic microcytic anemia with iron overload (AHMIO1), which has been described in eight patients so far. Here, we report two novel cases of this disease. The first proband is homozygous for a new SLC11A2 splicing variant (c.762 + 35A > G), becoming the first ever patient reported with a SLC11A2 splicing mutation in homozygosity. Splicing studies performed in this work confirm its pathogenicity. The second proband harbors the previously reported DMT1 G75R mutation in homozygosis. Functional studies with the G75R mutation in HuTu 80 cells demonstrate that this mutation results in improper DMT1 accumulation in lysosomes, which correlates with a significant decrease in DMT1 levels in patient-derived lymphoblast cell lines (LCLs). We also suggest that recombinant erythropoietin would be an adequate therapeutic approach for AHMIO1 patients as it improves their anemic state and may possibly contribute to mobilizing excessive hepatic iron.

Vitamin B12 deficiency and anemia in 140 Taiwanese female lacto-vegetarians.

BACKGROUND/PURPOSE: Lacto-vegetarians (LVs) tend to have vitamin B12 deficiency (B12D). This study assessed whether 140 female LVs, including 16 B12D/LVs and 124 non-B12D/LVs, had significantly higher frequencies of microcytosis, macrocytosis, and of blood hemoglobin (Hb), red blood cell (RBC), and serum vitamin B12 deficiencies than 140 healthy control subjects (HCSs). METHODS: The complete blood count and serum vitamin B12 level in 140 female LVs and 140 female HCSs were measured and compared. RESULTS: We found that 8.6%, 4.3%, 22.9%, 20.0%, and 11.4% of 140 LVs had microcytosis, macrocytosis, and blood Hb, RBC, and serum vitamin B12 deficiencies, respectively. The 140 LVs, 16 B12D/LVs, and 124 non-B12D/LVs had significantly higher frequencies of microcytosis as well as blood Hb and RBC deficiencies than 140 HCSs (all P-values < 0.005). Moreover, both 140 LVs and 124 non-B12D/LVs had significantly higher frequencies of macrocytosis than 140 HCSs. In this study, 32 (22.9%) of 140 LVs including 5 B12D/LVs and 27 non-B12D/LVs had anemia. Of the 5 anemic B12D/LVs, three had normocytic anemia, one had iron deficiency anemia (IDA), and one had thalassemia trait-induced anemia. Moreover, of the 27 anemic non-B12D/LVs, 18 had normocytic anemia, one had IDA, one had thalassemia trait-induced anemia, and 7 had microcytic anemia other than IDA and thalassemia trait-induced anemia. CONCLUSION: LVs have significantly higher frequencies of microcytosis, macrocytosis, blood Hb, RBC, and serum vitamin B12 deficiencies than HCSs. Normocytic and microcytic anemias are the two most common types of anemia in our LVs.

Microcytic anemia in children: parallel screening for iron deficiency and thalassemia provides a useful opportunity for thalassemia prevention in low- and middle-income countries.

Microcytic anemia in children is commonly attributed to iron deficiency without attempting to find the cause. Inadequate investigations to exclude hemoglobinopathies lead to missed opportunities for identification of thalassemia carriers. Here we aim to describe the relative contribution of iron deficiency and thalassemia to microcytic anemia in children. This hospital-based prospective study was conducted at the Colombo North Teaching Hospital, Ragama, Sri Lanka. All newly diagnosed patients with microcytic anemia were recruited and data were collected using an interviewer-administered questionnaire. Full blood count, blood film, serum ferritin, c-reactive protein, quantification of hemoglobin sub-types and α-globin genotype were performed using 4 ml of venous blood. A total of 104 children (Male- 60.5%) were recruited. Iron deficiency was the cause for anemia in 49% whilst 16% and 10% had α- and ß-thalassemia trait respectively. Seven (6.7%) children had co-existing iron deficiency and thalassemia trait while two coinherited α- and ß-thalassemia trait. Children with ß-thalassemia trait had significantly higher red cell count and lower mean corpuscular volume compared to children with iron deficiency. However, none of the red cell parameters were significantly different between children with α-thalassemia trait and iron deficiency. Iron deficiency contributes only to half of children with microcytic anemia; one-fourth had thalassemia trait. Co-existence of iron deficiency and thalassemia trait or co-inheritance of α- and ß-thalassemia trait were found in 9%. Parallel investigation of children with microcytic anemia to diagnose iron deficiency and thalassemia provides an opportunity to identify thalassemia carriers which is beneficial for thalassemia prevention.

Further Characterization of Hb Bronovo [α103(G10)His→Leu; HBA2: c.311A>T] and First Report of the Homozygous State.

Hb Bronovo [α103(G10)His→Leu, HBA2: c.311A>T] is an α-globin variant that interferes with and decreases binding efficiency to α hemoglobin (Hb) stabilizing protein (AHSP), a chaperone molecule. The histidine residue at position 103 is integral to the AHSP hydrogen bond formation where disruption results in an increased quantity of cytotoxic free α-globin chains, thereby creating a similar pathophysiology as ß-thalassemia (ß-thal). We report a family with Hb Bronovo, including a homozygous proband, which resulted from maternal uniparental disomy (UPD). Although not detected by routine studies in previous reports, the variant protein is visible by intact mass spectrometry (MS).

Heterozygosity for the Novel HBA2: c.*91_*92delTA Polyadenylation Site Variant on the α2-Globin Gene Expanding the Genetic Spectrum of α-Thalassemia in Iran.

There are four copy numbers of α-globin genes (16p13.3) in the human genome and the number of defective α-globin genes dictates the severity of α-thalassemia (α-thal). Mutations that occur in the 3' untranslated region (3'UTR), and especially at the polyadenylation (polyA) sites, affect the translation, stability and export of mRNA. A patient with hypochromic microcytic anemia was referred to the Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran by the health network. Molecular analysis of genomic DNA for the evaluation of mutations on the α- and ß-globin genes was performed. Direct sequencing of the hemoglobin (Hb) subunit α2 (HBA2) gene revealed a two nucleotide deletion between +816 and +817 in the 3'UTR, located at the polyA site, which seems to be a novel pathogenic variant. This novel variant expands the genetic spectrum of α-thal in the 3'UTR of the HBA2 gene.

Correlation of Red Blood Cell Acetylcholinesterase Enzyme Activity with Various RBC Indices.

Cholinesterases belongs to class hydrolases. There are two types acetylcholinesterase and butyryl cholinesterase. Acetylcholinesterase present in nerve endings and also in the RBC membrane. It helps to maintain the shape and size of RBCs. Any change in shape and size of RBCs may affect the activity of Acetylcholinesterase. Thus this study aimed to estimate RBCs Acetylcholinesterase enzyme activity in various types of anemias and correlate the RBCs Acetylcholinesterase enzyme activity with various hematological indices such as Erythrocyte Sedimentation Rate (ESR), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Volume (MCV), Red cell Distribution Width (RDW) etc. After obtaining ethical approval from Institutional ethics committee total of 100 samples were collected from Clinical Biochemistry laboratory, Kasturba Medical College, Manipal, Manipal University. 25 were having normal RBC indices, 12 with hemolytic anemia, 26 with microcytic anemia and 26 with macrocytic anemia based on peripheral smear report and RBC indices. Acetylcholinesterase were measured using Ellman's method. RBC acetylcholinesterase activity was significantly increased in microcytic anemia (58.13 ± 5.4) and macrocytic anemia (76.87 ± 6.7) than normal group (37.62 ± 2.71). Also increased RBC acetylcholinesterase was seen in hemolytic anemia (48.11 ± 5.18) but the increase is not statistically significant. RBC acetylcholinesterase correlated negatively with hemoglobin (r = -0.356, p = 0.001) and positively with RDW (r = 0.31, p = 0.003). To conclude RBC acetylcholinesterase activity can be used as one of the potential marker for various types of anemia.

Molecular diagnosis of α-thalassemia in a multiethnic population.

OBJECTIVE: α-Thalassemia, one of the most common genetic diseases, is caused by deletions or point mutations affecting one to four α-globin genes. Molecular diagnosis is important to prevent the most severe forms of the disease. However, the diagnosis of α-thalassemia is complex due to a high variability of the genetic defects involved, with over 250 described mutations. We summarize herein the findings of genetic analyses of DNA samples referred to our laboratory for the molecular diagnosis of α-thalassemia, along with a detailed clinical description. METHODS: We utilized a diagnostic algorithm including Gap-PCR, to detect known deletions, followed by sequencing of the α-globin gene, to identify known and novel point mutations, and multiplex ligation-dependent probe amplification (MLPA) for the diagnosis of rare or novel deletions. RESULTS: α-Thalassemia was diagnosed in 662 of 975 samples referred to our laboratory. Most commonly found were deletions (75.3%, including two novel deletions previously described by us); point mutations comprised 25.4% of the cases, including five novel mutations. Our population included mostly Jews (of Ashkenazi and Sephardic origin) and Muslim Arabs, who presented with a higher rate of point mutations and hemoglobin H disease. Overall, we detected 53 different genotype combinations causing a spectrum of clinical phenotypes, from asymptomatic to severe anemia. CONCLUSION: Our work constitutes the largest group of patients with α-thalassemia originating in the Mediterranean whose clinical characteristics and molecular basis have been determined. We suggest a diagnostic algorithm that leads to an accurate molecular diagnosis in multiethnic populations.

Evaluation of Applying a Combination of Red Cell Indexes and Formulas to Differentiate ß-Thalassemia Trait from Iron Deficiency Anemia in the Thai Population.

Red cell indexes and formulas have been established as simple, fast, and inexpensive tools to differentiate ß-thalassemia (ß-thal) trait from iron deficiency anemia. However, none of them showed 100.0% sensitivity and specificity. Moreover, one index may show greater sensitivity and specificity in one population but is ineffective in another population. This study evaluated the diagnostic reliability of a combination of two red cell indexes [red blood cell (RBC) and red blood cell distribution width (RDW)] and nine formulas called '11T score' for differentiation of ß-thal trait and iron deficiency anemia in the Thai population. A total of 103 cases, 67 ß-thal trait and 36 iron deficiency anemia, Thai subjects with microcytic hypochromic anemia [mean corpuscular volume (MCV) <80.0 fL and mean corpuscular hemoglobin (Hb) (MCH) <27.0 pg] were involved in this retrospective study. The results showed that the 11T score with a cutoff value of 7 was able to discriminate between ß-thal trait and iron deficiency anemia with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and efficiency (EFF) higher than 70.0%. It also had 85.4% of correctly identified cases and the highest value of Youden's Index (YI) (73.8%) when compared to the 11T score with other cutoff values (5, 6, 8 and 9) and other indexes. Thus, the 11T score with the cutoff value of 7 could be used to differentiate ß-thal trait from iron deficiency anemia in the Thai population.

Cut-Off Values of Hematologic Parameters to Predict the Number of Alpha Genes Deleted in Subjects with Deletional Alpha Thalassemia.

Most α-thalassemia cases are caused by deletions of the structural α-globin genes. The degree of microcytosis and hypochromia has been correlated with the number of affected α-globin genes, suggesting a promising role of hematologic parameters as predictive diagnostic tools. However, cut-off points for these parameters to discriminate between the different subtypes of α-thalassemia are yet to be clearly defined. Six hematologic parameters (RBC, Hb, MCV, MCH, MCHC and RDW) were evaluated in 129 cases of deletional α-thalassemia (56 heterozygous α⁺ thalassemia, 36 homozygous α⁺ thalassemia, 29 heterozygous α° thalassemia and 8 cases of Hb H disease). A good correlation between the number of deleted alpha genes and MCV (r = -0.672, p < 0.001), MCH (r = -0.788, p < 0.001) and RDW (r = 0.633, p < 0.001) was observed. The presence of an α° allele should be discarded in individuals with microcytosis without iron deficiency and normal values of Hb A2 and Hb F with MCH < 23.40 pg. Furthermore, MCH < 21.90 pg and/or MCV < 70.80 fL are strongly suggestive of the presence of one α° allele. Finally, an accurate presumptive diagnosis of Hb H disease can be made if both RDW ≥ 20% and MCH < 19 pg are seen.

Iron-refractory iron deficiency anemia (IRIDA) cases with 2 novel TMPRSS6 mutations.

Iron-refractory iron deficiency anemia (IRIDA) is a rarely diagnosed autosomal recessive disorder that presents with hypochromic, microcytic anemia due to mutations in TMPRSS6, which encodes matriptase-2. Contrary to classical iron deficiency anemia, serum hepcidin levels are found to be elevated in this disorder. Here, we report 5 cases from 4 unrelated families with inadequate response to iron therapy, who were consequently diagnosed as IRIDA. The mean age of the cases at diagnosis was 5.0 years (range: 0.7-11.3 years). All cases were either homozygous or compound heterozygous for missense or frameshift mutations in the TMPRSS6 gene, 2 of the mutations being novel (Cys410Ser and Leu689Pro). IRIDA should be considered in patients with findings of iron deficiency anemia unresponsive to oral iron therapy, whose serum ferritin levels are found normal or elevated.

Mild Microcytic Anemia in an Infant with a Compound Heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A).

We report an infant with a compound heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A) and a phenotype of mild microcytic anemia with target cell morphology but without overt hemolysis.

Identification of Mutations Causing Aberrant Termination and Deficient Splice Donor Site on the HBA1 Gene.

α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects on the α-globin gene cluster can result in α-thal that may develop a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. In the present study, four Iranian individuals with hypochromic microcytic anemia, who revealed none of the known mutations responsible for α-thal, were subjected for further investigations. The thalassemic phenotype of these patients resulted from abnormal RNA splicing sites owing to a missense at the splice donor site, a truncated protein or hemoglobin (Hb) variants as a result of two different substitutions on the α1-globin gene. The clinical presentation of mild anemia in these individuals showed the contribution of these novel mutations in α-thal in spite of the dominantly expressed α2-globin gene. This study describes hematological manifestations of subjects carrying some novel mutations comparable to the reported phenotype of α(+)-thal trait.

Hematinic deficiencies and anemia statuses in oral mucosal disease patients with folic acid deficiency.

BACKGROUND/PURPOSE: Folic acid deficiency (FAD) may result in macrocytic anemia. This study assessed the hematinic deficiencies and anemia statuses in oral mucosal disease patients with FAD (defined as folic acid ≤ 6 ng/mL). METHODS: The blood hemoglobin (Hb), iron, vitamin B12, and folic acid concentrations, serum gastric parietal cell antibody level, and mean corpuscular volume (MCV) in 198 oral mucosal disease patients with FAD were measured. Based on World Health Organization (WHO) criteria, anemia or Hb deficiency was defined as having an Hb concentration of <13 g/dL for men and <12 g/dL for women. In this study, macrocytic anemia due to FAD was defined as having an MCV ≥100 fL and folic acid ≤6 ng/mL; pernicious anemia as having MCV ≥100 fL, vitamin B12 < 200 pg/mL, and serum gastric parietal cell antibody positivity; iron deficiency anemia as having MCV <80 fL and iron <60 µg/dL; and thalassemia trait as having MCV <74 fL, red blood cell (RBC) count > 5.0 × 10(12)/L, and Mentzer index (MCV/RBC) < 13. RESULTS: We found that by WHO definitions, 73 (36.9%), 41 (20.7%), and 10 (5.1%) of our 198 FAD patients had concomitant Hb, iron, and vitamin B12 deficiencies, respectively. Of 73 anemic FAD patients, three had macrocytic anemia due to FAD, one had pernicious anemia, 14 had iron deficiency anemia, eight had thalassemia trait, and the resting 47 had normocytic anemia. CONCLUSION: In addition to macrocytic anemia (2.0%), FAD patients may have concomitant normocytic (23.7%) or microcytic (11.1%) anemia.

Mutations on the α2-Globin Gene That May Trigger α(+)-Thalassemia.

In the present study, a total of 11 individuals with hypochromic microcytic anemia who did not reveal the most common α-thalassemia (α-thal) deletions or mutations, were subjected to more investigations by DNA sequencing of the α-globin genes. Seven novel nondeletional α-thal mutations localized on the α2-globin gene in the heterozygous state were identified. These mutations either corrupted regulatory splice sites and consequently affected RNA processing or created unstable hemoglobin (Hb) variants. The mutations described here produced globin gene variants that lead to amino acid changes in critical regions of the globin chain. The clinical presentation of most patients was a persistent mild microcytic anemia similar to an α(+)-thal. In the last decade, numerous α-globin mutations have been observed leading to an α-thal phenotype and these studies have been considered to be important as discussed here.

Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts.

Abstract Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007) . Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of "total Al"assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al(+3) to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)(+2) and Al(H2O)6 (+3)] that after complexation with O2(•-), generate Al superoxides [Al(O2(•))](H2O5)](+2). Semireduced AlO2(•) radicals deplete mitochondrial Fe and promote generation of H2O2, O2 (•-) and OH(•). Thus, it is the Al(+3)-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer's disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances.

Frequency and Types of Anemia in Primary Hypothyroidism Patients: A Prospective Observational Study.

Background Primary hypothyroidism is a common endocrine disorder resulting from inadequate production of thyroid hormones. Anemia is a common condition that can occur in hypothyroidism. Anemia may occur due to nutrient deficiency, such as iron or vitamin B12 deficiency due to chronic disease in hypothyroidism. Therefore, it is important to evaluate the cause of anemia in hypothyroidism.  Objective The aim of this study was to determine the frequency of anemia and its types in patients with primary hypothyroidism. Methods This was a prospective cross-sectional observational study conducted at the Department of Medicine, Jinnah Postgraduate Medical Center, Karachi, Pakistan, using non-probability consecutive sampling. A total of 176 adults aged 18-65 years of either gender, newly diagnosed with primary hypothyroidism, or with any of its symptoms were included in the study. Patients already on anti-thyroid medication and with post-thyroidectomy hypothyroidism were excluded from the study. The duration of the study was 1.5 years, from January 2020 to July 2021. After ethical approval, written informed consent was obtained from each patient. Demographical data along with results of complete blood picture, including Hb and MCV for diagnosing anemia and its types were recorded on a pre-designed proforma. The chi-square test was applied keeping p < 0.05 as statistically significant. Results The mean age of the patients was 42.19 ± 8.43 years, with 59.66% (n = 105) females and 40.34% (n = 71) males. A total of 67% (n =118) patients were found to be anemic. Of these, 38.64% (n = 68) patients had normocytic anemia, 19.32% (n = 34) microcytic anemia, and 9.25% (n = 16) patients had macrocytic anemia; 56.34% (n = 40) males and 74.29% (n = 78) females were reported to be anemic (p = 0.01). Conclusion In our study, the frequency of anemia in patients with hypothyroidism was high, with normocytic anemia being the most common type. It is important to know the type of anemia in hypothyroidism, as normocytic anemia is due to the chronic disease process (anemia of chronic disease) and may not respond to nutrient supplementation. Conversely, microcytic anemia is commonly due to iron deficiency and macrocytic anemia is due to vitamin B12 deficiency and therefore, they require replacement therapy. In any case, it is important to identify and treat the underlying cause of anemia.

Prevalence and factors influencing anemia in women of reproductive age visiting a tertiary care hospital (Jinnah Postgraduate Medical Center) in Karachi: A cross-sectional study.

INTRODUCTION: Anemia is a significant public health concern, primarily affecting young children, pregnant and postpartum women, and menstruating adolescent girls and women. This study aimed to evaluate the prevalence of anemia and associated factors in women of reproductive age visiting a tertiary care hospital in Karachi, Pakistan. OBJECTIVE: The primary objective was to determine the prevalence of anemia in women of reproductive age, while the secondary objective was to investigate potential causes of anemia within this demographic group. DESIGN: A prospective cross-sectional approach was employed, adhering to Strengthening the Reporting of Observational Studies in Epidemiology guidelines. A questionnaire-based method was used to assess anemia, and data were collected from women aged 14 to 40 years. METHOD: The study was conducted at the Jinnah Postgraduate Medical Center from January to May 2023. The study was approved by the Institutional Review Board of Jinnah Sindh Medical University (Institutional Review Board reference number JSMU/IRB/2023/699). A sample of 397 women was included, and various demographic and lifestyle factors were assessed. RESULTS: In this study of 397 participants, 71.5% were found to have anemia, primarily microcytic anemia (48.2%). Anemia prevalence was highest among the 14-18 years age group (80.7%) and those from lower socioeconomic backgrounds (73.6%). Factors such as frequent tea consumption, irregular mealtimes, and pica consumption were associated with higher anemia rates. Pregnant women and those with more children were at a heightened risk of anemia. CONCLUSION: The study reveals a notable prevalence of anemia among women of reproductive age with a surprising emphasis on younger individuals and lower socioeconomic groups. Dietary habits, lifestyle choices, and pregnancy status play significant roles in anemia development. Targeted interventions are essential, particularly for younger women, those from disadvantaged backgrounds, and pregnant individuals, to combat anemia effectively in this region.

Anemia is a widespread health concern, especially in young children, pregnant women, and menstruating adolescent girls. This condition, characterized by low hemoglobin levels, leads to insufficient oxygen delivery to organs. Globally, nearly 30% of women of reproductive age suffer from anemia, with a higher prevalence in certain regions such as Pakistan. This study aimed to assess anemia prevalence and associated factors among women of reproductive age in Karachi, Pakistan. Of the 397 participants, 71.5% were anemic. Microcytic anemia was more prevalent than macrocytic anemia. Various factors contributed to anemia, including age (highest prevalence in 14 to 18 years), lower socioeconomic status, irregular meal times, and frequent tea consumption. Surprisingly, individuals who consumed iron supplements exhibited a higher prevalence of anemia. Factors contributing to higher rates of anemia included frequent tea consumption, irregular mealtimes, and the consumption of non-nutritive substances (pica). Pregnant women and those with more children were identified as having an increased risk of anemia. In addition, women with hectic schedules were more prone to anemia. These results highlight the importance of lifestyle choices, dietary habits, and pregnancy status in the development of anemia. The study underscores the need for targeted interventions to address anemia effectively, with a particular focus on younger women, individuals from disadvantaged backgrounds, and pregnant women. By understanding the specific factors contributing to anemia in this population, public health strategies can be tailored to address the unique needs of these groups, ultimately improving the overall health outcomes for women of reproductive age in the region.