Association of Serum Ferritin, Folate, Vitamin B12 with Thyroid Hormone Levels in Patients with Thyroid Disorders.

INTRODUCTION: Anemia frequently occurs during course of clinical thyroid diseases. Without proper diagnosis & effective treatment of underlying thyroid disease, it is often difficult to achieve complete correction of anemia. AIM: The present study was conducted to assess prevalence & types of anaemia in patients with thyroid disorders. MATERIALS: A cross sectional study was conducted on 160 patients including both hypothyroid & hyperthyroid patients at OPD/IPD in SRN Hospital affiliated to MLN Medical college Prayagraj between July 2021 & August 2022. Blood samples were taken to estimate CBC, GBP with Retic count, S. ferritin, S. folate, S. Vitamin B12, Thyroid profile. Data was entered in MS Excel Spreadsheet & appropriate statistical package applied. RESULT: Out of 144 hypothyroid patients, 102 (70.83%) were found to be anaemic & out of 16 hyperthyroid patients, 6 (37.5%) were found to be anaemic. In 102 anaemic hypothyroid patients, 56 (54.9%)had normocytic normochromic, 25 (24.5%) had microcytic and 21 (20.5%) had macrocytic anaemia. In 6 anaemic hyperthyroid patients, 3 (50%) had normocytic normochromic, 2(33.33%) had microcytic and 1 (16.67%) had macrocytic anaemia. CONCLUSION: High prevalence of anaemia was found in patients with thyroid disorders. Anaemia is an uncommon finding in hyperthyroidism but when present may be similar to that present in hypothyroidism. The most common type of anaemia in both hyperthyroidism & hypothyroidism was found to be normocytic normochromic, followed by microcytic & least common being macrocytic. References Suhail N, Abu Alsel BT, Batool S. Prevalence and association of thyroid dysfunction with anemia/body iron status among northern border Saudi population. Int J Med Res Health Sci 2020;9(3):1-7. Peraka SA, Karre S, Ravuri S, et al., To evaluate prevalence of anemia in hypothyroid patients. J Diagn Pathol Oncol 2019;4(2):110-113.

Haemoglobin levels and outcomes of subgroups of patients with pre-operative anaemia based on red cell size: A retrospective cohort study.

BACKGROUND: Pre-operative anaemia is common and associated with adverse outcomes. We hypothesised that pre-operative anaemia would be evident more than 1 month pre-operatively, and that peri-operative changes in haemoglobin and post-operative outcomes differed between red cell size-based subsets of anaemia. METHODS: A retrospective single-centre cohort study, including all patients 18 years and older undergoing their first surgery at Landspitali between January 2006 and December 2018 with available measurement of haemoglobin (Hb) within 30 days preceding surgery. Clinical data were compared between patients with subgroups of anaemia classified by mean corpuscular volume (MCV) into microcytic (MCV < 80 fl), normocytic (MCV 80-100 fl), and macrocytic (MCV > 100 fl) anaemia. The development of haemoglobin measurements from a nationwide database was plotted from 1 year pre-operatively to 2 years post-operatively. RESULTS: Of 40,979 patients, 10,505 (25.6%) had pre-operative anaemia, of which 1089 (10.4%) had microcytic anaemia, 9243 (88.0%) had normocytic anaemia, and 173 (1.6%) had macrocytic anaemia. Patients within all subgroups of pre-operative anaemia had a higher degree of comorbidity and frailty burden and a low haemoglobin evident for more than 100 days pre-operatively and similar changes post-operatively. Post-operative prolonged recovery of haemoglobin was slower for macrocytic anaemia than other types of anaemia. All groups of patients with anaemia had a higher incidence of 30-day mortality, acute kidney injury, and rate of readmission compared with patients without anaemia. CONCLUSIONS: Pre-operative anaemia is evident long prior to the procedure and its association with worse outcomes is similar regardless of red cell size.

Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric Hematology-Oncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics.

JUSTIFICATION: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. OBJECTIVE: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. PROCESS: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. RECOMMENDATIONS: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

Does serum gastric parietal cell antibody titer have influence on anemia and vitamin B12 deficiency in atrophic glossitis patients?

BACKGROUND/PURPOSE: Our previous study found 284 gastric parietal cell antibody (GPCA)-positive atrophic glossitis (AG) patients (so-called GPCA+AG patients in this study) in a group of 1064 AG patients. This study evaluated whether high-titer (GPCA titer ≥ 160) GPCA+AG patients had greater frequencies of anemia, vitamin B12 deficiency, macrocytosis, and hyperhomocysteinemia than low-titer (GPCA titer < 160) GPCA+AG patients. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 117 high-titer GPCA+AG patients, 167 low-titer GPCA+AG patients, and 532 healthy control subjects were measured and compared. RESULTS: We found that 12.0%, 29.1%, 23.1%, 16.2%, 1.7%, and 23.1% of 117 high-titer GPCA+AG patients and 5.4%, 17.4%, 17.4%, 7.2%, 1.2%, and 14.4% of 167 low-titer GPCA+AG patients were diagnosed as having macrocytosis, blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia, respectively. Moreover, both 117 high-titer and 167 low-titer GPCA+AG patients had significantly greater frequencies of macrocytosis, blood hemoglobin, serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than 532 healthy control subjects (all P-values < 0.05). In addition, 117 high-titer GPCA+AG patients also had greater frequencies of anemia (P = 0.029, statistically significant), serum vitamin B12 deficiency (P = 0.027, statistically significant), macrocytosis (P = 0.075, marginal significance), and hyperhomocysteinemia (P = 0.085, marginal significance) than 167 low-titer GPCA+AG patients. CONCLUSION: For GPCA+AG patients, high-titer GPCA+AG patients have greater frequencies of anemia, serum vitamin B12 deficiency, macrocytosis, and hyperhomocysteinemia than low-titer GPCA+AG patients.

Progressive myeloneuropathy with symptomatic anaemia.

Hypocupremia is a rare and under-recognised cause of bone marrow dysplasia and myeloneuropathy. A 47-year-old Caucasian woman had progressive ascending peripheral neuropathy and gait ataxia over 3 months and fatigue, dyspnoea and unintentional weight loss over 8 months. She had profound macrocytic anaemia and neutropenia. Initial workup included normal serum vitamin B12 Bone marrow biopsy was suggestive of copper deficiency. Serum copper levels were later confirmed to be undetectable. The patient received oral copper repletion which resulted in complete normalisation of haematological abnormalities 16 weeks later. However, neurological deficits persisted. This case describes a delayed diagnosis of hypocupremia as initially suggested through invasive testing. Associating myeloneuropathy with cytopenia is imperative for accurate and prompt diagnosis of hypocupremia, which can be confirmed by serum analysis alone. Developing an accurate differential diagnosis can help prevent unnecessary procedures. Furthermore, initiating prompt copper repletion prevents further neurological impairment. Neurological deficits are often irreversible.

[Diagnosis of anemia associated with alcoholic cirrhosis]. / Diagnostic différentiel de l'anémie dans la cirrhose éthylique.

We report here the case of a 62-year-old patient with Child-Pugh stage C ethylic cirrhosis associated with severe macrocytic anaemia, refractory to iterative transfusions and withdrawal. After a haemorrhagic, deficiency-related, or sideroblastic etiology was ruled out, haemolytic anaemia was suspected. A blood smear allowed diagnosis of haemolytic anaemia with acanthocytes. This offers the opportunity to discuss anaemia in patients with alcoholic cirrhosis, a frequent complication spanning a broad severity range and having the potential to be life-threatening. Its origin can be multifactorial : acute haemorrhage, dilution, haemolysis (here due to acanthocytosis), marrow insufficiency caused by direct alcohol toxicity, malnutrition, iron deficiency, vitamin B9 or B12 deficiency, chronic inflammation, splenic sequestration induced by portal hypertension...

Nous rapportons le cas d'une patiente de 62 ans atteinte d'une cirrhose éthylique de stade Child-Pugh C associée à une anémie macrocytaire sévère, réfractaire aux transfusions itératives et au sevrage. Après avoir exclu les étiologies hémorragiques, carentielles et sidéroblastiques, une anémie hémolytique (AH) est suspectée. La réalisation d'un frottis sanguin a permis le diagnostic d'une anémie hémolytique à acanthocytes. L'opportunité nous est donnée de discuter de l'anémie chez le patient cirrhotique alcoolique, complication fréquente recouvrant un large spectre de gravité et pouvant menacer la survie. Elle peut être multifactorielle : hémorragie aiguë, dilution, hémolyse (dans le cas particulier, liée à une acanthocytose), insuffisance médullaire par toxicité directe de l'alcool, malnutrition, carence martiale, déficit en vitamine B9 ou B12, inflammation chronique, séquestration splénique induite par l'hypertension portale….

Hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with macrocytosis.

BACKGROUND/PURPOSE: Macrocytosis is defined as having the mean corpuscular volume (MCV) â‰§ 100 fL. This study evaluated whether 41 atrophic glossitis (AG) patients with macrocytosis had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 532 healthy control subjects or 1064 AG patients. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 41 AG patients with macrocytosis, 1064 AG patients, and 532 healthy control subjects were measured and compared. RESULTS: We found that 73.2%, 22.0%, 73.2%, 4.9%, 80.5%, and 56.1% of 41 AG patients with macrocytosis were diagnosed as having blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Moreover, 41 AG patients with macrocytosis had significantly higher frequencies of blood hemoglobin and serum vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects or 1064 AG patients (all P-values < 0.001). In addition, 41 AG patients with macrocytosis also had significantly higher frequencies of serum iron and folic acid deficiencies than 532 healthy control subjects (both P-values < 0.001). Pernicious anemia was found in 22 AG patients with macrocytosis. CONCLUSION: There are significantly higher frequencies of anemia and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients with macrocytosis than in healthy control subjects. AG patients with macrocytosis also have significantly higher frequencies of blood hemoglobin and serum vitamin B12 deficiencies, hyperhomocysteinemia, and serum GPCA positivity than AG patients.

MDS with 5q deletion and rare cKIT positive mastocytosis: a diagnostic and therapeutic challenge.

A patient with a diagnosis of myelodysplastic syndrome (MDS) with isolated 5q deletion underwent repeat bone marrow biopsy to assess haematological response after 6 months of initial lenalidomide therapy. Subsequent bone marrow biopsies revealed persistent MDS with del(5q) in addition to a small atypical mast cell population with >25% of mast cells with spindle-shaped morphology and immunohistochemistry characteristics consistent with mastocytosis. Molecular testing on the bone marrow was positive for cKIT D816V and the patient was diagnosed with systemic mastocytosis (SM) with an associated haematological neoplasm. MDS with SM is well known to be associated; however, to the best of our knowledge, only one prior case report identifies MDS with del(5q) and associated cKIT D816V positive mastocytosis. While the exact clonal origin of both chromosomal aberrations is unclear, this case illustrates the therapeutic efficacy of lenalidomide in a patient with MDS with del(5q) and rarely associated cKIT positive SM.

Vitamins B12 and D deficiencies and macro- and microelement disturbances among diabetic elderly patients.

Vitamin and mineral disturbances may interfere with glucose metabolism. Elderly persons with diabetes type 2 (T2DM) are more prone to mineral disturbances and vitamin deficiencies. The aim of this study was to analyze concentrations of vitamins B12 and D and macro- and microelements among diabetic elderly patients. The study enrolled 347 patients with T2DM of whom 247 were elderly (median 76 years of age) (SenDM group) and 100 younger T2DM (median 59 years of age) (Y-DM group), and 320 patients aged 65 years and above without T2DM (mean 77 years of age) - Sen-nonDM - as a control group. Patient clinical and biochemical characteristics were recorded (drugs taken and glucose concentration, glycated hemoglobin level, complete blood count, concentration of Na, K, Ca, Fe and serum vitamins D and B12 levels). All elderly patients had insufficient/deficient vitamin D concentration. Vitamin B12 levels were below the reference limit for 15.6% of the SenDM group. No significant differences in Na, K, were observed among the investigated groups. 30.7% of the SenDM were Fe-deficient. In the SenDM group, vitamin B12-deficient patients did not develop macrocytic anaemia while Fe-deficient patients with T2DM tended to develop microcytic anaemia. The prevalence of vitamin deficiencies in elderly patients with T2DM is clinically relevant. Elderly patients with T2DM are clinically predisposed to Fe deficiencies. We suggest to monitor vitamin B12 and Fe concentration toward developing a full clinical picture as it may accelerate the treatment options and improve elderly patients' outcome.

Macrocytic anemia is associated with the severity of liver impairment in patients with hepatitis B virus-related decompensated cirrhosis: a retrospective cross-sectional study.

BACKGROUND: Macrocytic anemia is common in liver disease. However, its role in hepatitis B virus (HBV)-related decompensated cirrhosis remains unknown. The aim of the present study was to determine the association between macrocytic anemia and the severity of liver impairment in patients with HBV-related decompensated cirrhosis according to the Model for End Stage Liver Disease (MELD) score. METHODS: A total of 463 participants who fulfilled our criteria were enrolled in this cross-sectional study. Patients were classified into three groups according to anemia types, diagnosed based on their mean corpuscular volume level. Multivariate linear regression analyses were used to determine the association between macrocytic anemia and the MELD score for patients with HBV-related decompensated cirrhosis. RESULTS: Patients with macrocytic anemia had evidently higher MELD scores (10.8 ± 6.6) than those with normocytic anemia (8.0 ± 5.5) or microcytic anemia (6.3 ± 5.1). The association remained robust after adjusting for age, gender, smoking, drinking, and total cholesterol (ß = 1.94, CI: 0.81-3.07, P < 0.001). CONCLUSIONS: Macrocytic anemia was found to be associated with the severity of liver impairment and might be a predictor for short-term mortality in patients with HBV-related decompensated cirrhosis.

Thrombotic Microangiopathy-Like Hemolysis in Vitamin B12 Deficiency-Related Macrocytic Anemia.

BACKGROUND: Hemolytic features in patients with pernicious anemia have not been emphasized. METHODS: Seven Japanese patients at 60 - 88 years of age with vitamin B12 deficiency-related hemolytic anemia were assessed. RESULTS: Serum vitamin B12 levels in these cases were 46 - 89 pg/mL (normal reference range: 233 - 914 pg/mL). Clinically, the patients presented with thrombotic microangiopathy (TMA)-like hemolytic features (including macrocytic anemia, schistocytes on blood smears, high serum lactate dehydrogenase, hyperbilirubinemia, and low serum haptoglobin). Six cases had type A gastritis (assessed by esophagogastroduodenoscopy with hypergastrinemia) with additional laboratory data of high plasma homocysteine levels and anti-intrinsic factor/anti-parietal cell antibodies. One case was in post-gastrectomy condition. Following treatment with vitamin B12, anemia resolved within 4 weeks in five of the seven cases except for two cases of delayed response. CONCLUSIONS: In elderly patients exhibiting hemolytic features in association with macrocytic anemia, vitamin B12 deficiency should be considered in the differential diagnosis.

Sanjad-Sakati syndrome with macrocytic anemia and failure to thrive: a case from South Jordan.

Backgorund: Sanjad-Sakati syndrome (SSS) is a rare autosomal recessive disease caused by a deletion mutation (155-166del) in exon 3 of the TBCE gene on chromosome 1q42-43. The syndrome is characterized by primary hypoparathyroidism, typical dysmorphic features and severe growth retardation. CASE PRESENTATION: We encountered a 2-year-old boy with hypocalcemia, failure to thrive and macrocytic anemia. The patient had the characteristic features of SSS and genetic testing confirmed that he was homozygous for the TBCE mutation. Although malabsorption was initially considered the cause of his symptoms, the results did not confirm that diagnosis. Our patient had cow milk protein allergy and folic acid deficiency, which has not been described in previous SSS cases. It was difficult to treat the patient's hyperphosphatemia and we ultimately selected sevelamer treatment, which was tolerated well and improved his hypocalcemia. CONCLUSIONS: SSS should be considered in the differential diagnosis of any infant with hypocalcemia, dysmorphism and failure to thrive.

Folate deficiency in patients seeking treatment of alcohol use disorder.

INTRODUCTION: Nutritional deficiency is frequent in patients with an alcohol use disorder (AUD). We aimed to analyze serum and erythrocyte folate deficiency in a case series of patients that initiated treatment of AUD. PATIENTS AND METHODS: A cross-sectional study in patients admitted for detoxification between 2007 and 2015 was performed. Sociodemographic characteristics, history of alcohol consumption, type of alcohol, and medical co-morbidity were assessed at admission. Blood samples for biochemistry and hematological parameters were collected at admission. Logistic regression models were used to establish predictors of folate deficiency. RESULTS: 211 patients (79.1% men) were eligible; age at admission was 46 years [IQR:40-51], and the amount of alcohol consumption was of 160g/day [IQR:120-200]. Thirty four percent of patients had macrocytosis (MCV>100fL), 12.8% had anemia, 23% of cases presented with serum folate deficiency and 7% presented with erythrocyte folate deficiency. Most (69%) of the patients with serum folate deficiency had normal erythrocyte folate levels. In univariate analysis, macrocytosis (OR=3.4, 95%CI:1.7-6.6), alcohol-related liver disease (ARLD) (OR=2.5, 95%CI:1.0-6.1) and drinking alcoholic beverages other than beer (OR=3.3, 95%CI:1.5-7.3) were associated with folate deficiency. However, only macrocytosis was significantly associated with serum folate deficiency in multivariate analysis (OR=3.1, 95%CI:1.1-8.9). Macrocytosis (P<0.001), ARLD (P=0.01) and the type of alcohol consumption (P<0.001) were factors associated with erythrocyte folate deficiency in univariate analysis. In multivariate analysis only macrocytosis remained significantly associated to erythrocyte folate deficiency (P=0.037). CONCLUSION: Folate deficiency is a relatively frequent finding in contemporary, middle-aged patients with AUD, and macrocytosis is significantly associated with the deficiency.

Constitutional Trisomy 8 Mosaicism with Persistent Macrocytosis.

Constitutional trisomy 8 mosaicism (CT8M) is a rare chromosomal abnormality. The phenotype varies from normal features to severe malformations. CT8M increases the risk of developing leukemia and myelodysplastic syndrome. As CT8M is very rare, its diagnosis can easily be overlooked, especially in cases with mild phenotypes. Here, we report the diagnostic process of a 40-year-old female patient with CT8M and discuss the importance of follow-up in monitoring for hematological malignancies.

A Zebrafish Model of 5q-Syndrome Using CRISPR/Cas9 Targeting RPS14 Reveals a p53-Independent and p53-Dependent Mechanism of Erythroid Failure.

5q-syndrome is a distinct form of myelodysplastic syndrome (MDS) where a deletion on chromosome 5 is the underlying cause. MDS is characterized by bone marrow failures, including macrocytic anemia. Genetic mapping and studies using various models support the notion that ribosomal protein S14 (RPS14) is the candidate gene for the erythroid failure. Targeted disruption of RPS14 causes an increase in p53 activity and p53-mediated apoptosis, similar to what is observed with other ribosomal proteins. However, due to the higher risk for cancer development in patients with ribosome deficiency, targeting the p53 pathway is not a viable treatment option. To better understand the pathology of RPS14 deficiency in 5q-deletion, we generated a zebrafish model harboring a mutation in the RPS14 gene. This model mirrors the anemic phenotype seen in 5q-syndrome. Moreover, the anemia is due to a late-stage erythropoietic defect, where the erythropoietic defect is initially p53-independent and then becomes p53-dependent. Finally, we demonstrate the versatility of this model to test various pharmacological agents, such as RAP-011, L-leucine, and dexamethasone in order to identify molecules that can reverse the anemic phenotype.

Ovarian Microcystic Stromal Tumor: A Rare Clinical Manifestation of Familial Adenomatous Polyposis.

Microcystic stromal tumor (MST) is a rare tumor of presumed sex-cord stromal differentiation. We present a case of MST arising within a patient with constitutional 5q deletion syndrome, whose deletion encompassed the APC gene. Genomic analysis of the MST revealed a point mutation in the remaining APC allele, predicted to result in abnormal splicing of Exon 7. Subsequent clinical investigation revealed multiple gastrointestinal polyps qualifying for a diagnosis of familial adenomatous polyposis. This case emphasizes the importance of an aberrant Wnt/ß-catenin pathway in the development of MST and adds credence to the inclusion of MST as a rare phenotype of familial adenomatous polyposis. In a search for additional genetic aberrations which may contribute to the development of this rare tumor, genomic analysis revealed a frameshift mutation in FANCD2, a protein which plays a key role in DNA repair. This protein is expressed in human ovarian stromal cells and FANCD2-knockout mice are known to develop sex cord-stromal tumors, factors which further support a possible role of aberrant FANCD2 in the development of MST.