Macrocytic Hyperchromic Anemia Research Articles

VEXAS and Myelodysplastic Syndrome: An Interdisciplinary Challenge.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized systemic autoinflammatory disease caused by somatic mutations in hematopoietic progenitor cells. This case series of four patients with VEXAS syndrome and comorbid myelodysplastic syndrome (MDS) aims to describe clinical, imaging, and hematologic disease presentations as well as response to therapy. Four patients with VEXAS syndrome and MDS are described. A detailed analysis of imaging features, hemato-oncological presentation including bone marrow microscopy and clinical-rheumatological disease features and treatment outcomes is given. All patients were male; ages ranged between 64 and 81 years; all were diagnosed with MDS. CT imaging was available for three patients, all of whom exhibited pulmonary infiltrates of varying severity, resembling COVID-19 or hypersensitivity pneumonitis without traces of scarring. Bone marrow microscopy showed maturation-disordered erythropoiesis and pathognomonic vacuolation. Somatic mutation in the UBA1 codon 41 were found in all patients by next-generation sequencing. Therapy regimes included glucocorticoids, JAK1/2-inhibitors, nucleoside analogues, as well as IL-1 and IL-6 receptor antagonists. No fatalities occurred (observation period from symptom onset: 18-68 months). Given the potential underreporting of VEXAS syndrome, we highly recommend contemporary screening for UBA1 mutations in patients presenting with ambiguous signs of systemic autoinflammatory symptoms which persist over 18 months despite treatment. The emergence of cytopenia, especially macrocytic hyperchromic anemia, should prompt early testing for UBA1 mutations. Notably conspicuous, pulmonary alterations in CT imaging of patients with therapy-resistant systemic autoinflammatory symptoms should be discussed in interdisciplinary medical teams (Rheumatology, Hematology, Radiology and further specialist departments) to facilitate timely diagnosis during the clinical course of the disease.

492. TYPES AND INCIDENCE OF POSTOPERATIVE ANEMIA AFTER ONCOLOGICAL ESOPHAGECTOMY AND GASTRECTOMY

Abstract According to current literature, anemias that develop after oncological esophageal and gastric resections are classified as deficiency anemias. Due to the surgery-related changes in the mechanical and biochemical conditions of the upper gastrointestinal tract, there is an alteration in the processing and absorption of hematopoietic-relevant vitamins and trace elements like iron, vitamin B6, vitamin B12, folic acid, copper and essential amino acids in the postoperative phase. Between January 2015 and December 2019, 232 patients underwent a (sub)total gastrectomy or esophagectomy at our center. In this monocentric retrospective analysis of prospectively collected follow-up data, 157 patients were included after applying the exclusion criteria: Age below 18, primary bone marrow disease, hereditary forms of anemia, postoperative tumor recurrence and R1/R2 situation. 103 patients (=66%) belonged to the esophagectomy group and 54 patients (=34%) to the (sub)total gastrectomy group. Preoperatively and three, six, twelve, 18, and 24 months postoperatively the following laboratory parameters were collected and descriptively analyzed: Hemoglobin, MCV, MCH, serum iron, ferritin, transferrin, and vitamin B12. Two years after the oncological resection 28% of patients with esophagectomy, EE, and 48% of patients with (sub)total gastric resection, (S)GE, show anemia. Normocytic anemia was the dominant type. The MCV distribution of anemic patients in the EE group was as follows: 3% microcytic, 77% normocytic, and 20% macrocytic. The anemic patients in the (S)GE group show the following MCV distribution: 16% microcytic, 81% normocytic, and 3% macrocytic. The (S)GE collective has more anemic patients in percentage terms than the EE collective throughout the whole follow-up period. This difference is significant at the 12th (p = 0.032) and 18th-month (p = 0.023) postoperative follow-up. A high percentage of patients with oncological resection of the upper gastrointestinal tract have a relevant postoperative anemia. The known postoperative iron and vitamin deficiencies, that would be associated with microcytic hypochromic and macrocytic hyperchromic anemia, are not the relevant causes for this anemia as it is predominantly a normocytic form. Normocytic anemia is an indication for an anemia of chronic disease. The reason for the predominance of normocytic anemia is not specifically known.

Anemia among Children Aged 1 month -12 Years at Al-Wahda Hospital, Derna-Libya

Anemia is one of the main public health issues among children in the world. The causes of anemia are multifactorial, but iron deficiency is the most common one. There are direct proportions between iron and body mass. The paper aimed at determining anemia prevalence in children aged 1-144 months in Al-wahda Hospital in Derna city during the first quarter of 2017, as well as determining the type of anemia. A sample of 129 children aged 1-144 M was tested for hemoglobin levels to diagnose anemia. Mean corporal values were measured to determine the type of anemia, and data were collected based on independent variables such as age and sex. The frequency was created, and comparisons were tested using chi-square. Anemia prevalence of overall sample was 65.11%. It was significantly higher in children aged (1-3 months) than those aged (4-6 months), and (7-144 months) (p =.001). Significant differences were found in anemia prevalence among boys and girls, where prevalence was higher in girls than in boys (P=.008). Prevalence of Microcytic hypochromic anemia was higher (69.4 %) compared to Normocytic normochromic (28.57%), and Macrocytic hyperchromic anemia (2.38%). Prevalence of anemia of the overall sample is considered as sever based on World Health Organization anemia classification. In addition, increased anemia prevalence in children less than 3 months shud be taken care of the Libyan government to prevent and control anemia in pregnant women. The high prevalence of Microcytic hypochromic in the overall sample was observed. Further estimation of iron and ferritin should do, and further evalution is needed to identify the causes of anemia in children under 12 years.

Heme-Regulated eIF2α Kinase Coordinates Translational Repression of eIF2αP and mTORC1 Signaling during Iron Deficiency to Mitigate Ineffective Erythropoiesis

Iron deficiency anemia (IDA) is a prevalent disease, yet molecular mechanisms by which iron and heme regulate erythropoiesis are not well understood. Heme-regulated eIF2α kinase (HRI) is a hemoprotein highly expressed in erythroid precursors. HRI senses intracellular heme concentrations to ensure that globin synthesis does not exceed the amount of heme available for hemoglobin production. In heme deficiency, HRI is activated and phosphorylates eIF2α, which inhibits the translation of globin mRNAs as well as enhances selectively the translation of activating transcription factor 4 (ATF4) mRNA to induce transcription of stress response genes. Previously, we reported that HRI is also necessary to promote erythroid differentiation during iron deficiency (ID). To further interrogate the molecular mechanism of HRI-eIF2αP-ATF4 signaling in erythropoiesis, we generated a novel mouse model (eAA mice) that lacks of eIF2α phosphorylation (eIF2αP) by substituting serine 51 residue with alanine specifically in the erythroid lineage. eAA mice did not display significant erythroid phenotypes during normal adult steady-state erythropoiesis. However, eAA mice developed ineffective erythropoiesis with splenomegaly and macrocytic hyperchromic anemia in ID, similar to Hri-/- mice. In contrast, iron deficient Atf4-/- mice developed more severe anemia, and were microcytic hypochromic. Thus, regulation of cell size and hemoglobin content of RBCs by HRI is mediated through eIF2αP and not ATF4. Consistent with the regulation of globin translation by eIF2αP, globin inclusions were present in reticulocytes of eAA mice, but not Atf4-/- mice. Both eAA and Atf4-/- mice exhibited inhibition of terminal erythroid differentiation starting at basophilic erythroblasts in ID. The ROS levels in RBCs and reticulocytes were elevated, demonstrating that HRI-eIF2αP-ATF4 signaling contributes significantly to mitigation of oxidative stress in late stage erythroid cells. Our results demonstrate for the first time that both eIF2αP and ATF4 are necessary for iron-restricted erythropoiesis.mTORC1 (mechanistic target of rapamycin complex 1) signaling in blood cells was recently reported to be down regulated in ID. Furthermore, constitutively activated mTORC1 signaling in the hematopoietic lineage results in macrocytic hyperchromic anemia with splenomegaly (similar to our ID Hri-/- and eAA mice) whereas inactivation of mTORC1 signaling results in microcytic hyperchromic anemia, characteristics of IDA in Wt mice (Knight et al. eLife 2014). We therefore investigated whether HRI stress signaling was necessary to down-regulate mTORC1 in ID. mTORC1 signaling increases protein synthesis by phosphorylating eIF4E binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (S6K), which phosphorylates S6. We found that mTORC1 signaling activities as measured by pS6 and p4E-BP1, were higher in iron deficient Hri-/-, eAA and Atf4-/-erythroid precursors in comparison to Wt cells. Treatment of iron deficient Hri-/-, eAA and Atf4-/-mice with rapamycin, an mTORC1 inhibitor, increased RBC counts and hemoglobin content in the blood, improved erythroid differentiation and reduced splenomegaly significantly. However, globin inclusions remained visible in Hri-/- and eAA reticulocytes, indicating a non-redundant role of HRI-eIF2αP in inhibiting globin translation. Dietary iron repletion of the iron deficient mice rapidly and completely reversed the anemia in 10 days by promoting erythroid differentiation and decreasing HRI and mTORC1 signaling in Hri-/-, eAA and Atf4-/-mice. Furthermore, the elevated serum erythropoietin (EPO) levels in our ID anemic mice were decreased significantly upon rapamycin treatment or iron repletion. Together, our results demonstrate that HRI is indispensible for both the activation of the eIF2αP-ATF4 signaling and the repression of mTORC1 signaling during ID to circumvent ineffective erythropoiesis and macrocytic anemia. Our findings also indicate that HRI stress signaling could serves as a feedback mechanism for EPO signaling by inhibiting mTORC1. This study provides molecular insights into the role of heme and translation in the regulation of erythropoiesis and may provide novel targets for the treatment of hemoglobinopathies. DisclosuresNo relevant conflicts of interest to declare.

Effects of Acute Exposure to Endosulfan (Organochlorine Pesticides) on Hematology of African Mud Catfish, Clarias gariepinus (Burchell, 1822).

Changes in the blood parameters of fingerlings of Clarias gariepinus were investigated after 24 and 96-h of exposures to endosulfan. 180 fingerlings of C. gariepinus [mean weight (10.5±1.3 g); total length (11.2±1.2 cm)] were exposed to five different concentrations (1.00, 2.20, 4.80, 11.00, 23.00 µg/L) of endosulfan and a control for 96 h after being acclimatized for 21 days. After 24 h of exposure, microcytic hypochromic anemia was observed and all erythrocyte profiles tested showed significant variation (p<0.05) among the treatments except thrombocyte and mean corpuscular hemoglobin concentration. Macrocytic hyperchromic anemia was noticed after 96 h of exposure and all the hematological parameters varied significantly (p<0.05) except packed cell volume and red blood cell count. The study shows that endosulfan alters the hematology of C. gariepinus fingerlings. Therefore, awareness on the hazards associated with the use of endosulfan should be intensified and sound sustainable alternatives to endosulfan should be developed.

Chronic Haemolytic Anemia and Splenomegaly in a Patient with an Isolated Adrenocorticotropin Deficiency

Herein we describe a case of a 56-years old patient presented with general malaise, anorexia and progressive weight loss for about 5years associated recently with diarrhoea and repeated syncopal attacks for 1month. On admission, he had splenomegaly and his laboratory studies showed macrocytic hyperchromic haemolytic anemia [Hb = 9.4g/dl] and a significant hyponatremia [Na+ = 111mmol/l]. Endocrinological evaluation revealed an isolated adrenocorticotropin deficiency (IAD) with a manifest hypoaldosteronism. On treatment with cortisone, both anemia and hyponatremia (but not splenomegaly) were markedly improved. Our case may represent an evidence for the pathogenesis of erythropoietic dysfunction in patients of adrenocortical insufficiency.

SYNTHETIC FOLIC ACID THERAPY IN PERNICIOUS ANEMIA

Our purpose in this communication is to show the responses of 6 unselected patients with addisonian pernicious anemia to various doses of synthetic folic acid as reflected by changes in the hemoglobin and the red cell and reticulocyte counts. The experimental and laboratory data on the clinical and biologic activities of the Lactobacillus casei factor have been thoroughly discussed by Moore and his associates 1 and the clinical aspects of folic acid in the treatment of patients with macrocytic hyperchromic anemia were recently reported by Spies. 2 Further evaluation of the antianemic properties have been added by Doan and his associates 3 and by Spies. 4 METHODS OF STUDY All patients in this series were hospitalized during the full period of observation. Control intervals of from three to nine days were required for investigation and diagnosis. The diagnosis of addisonian pernicious anemia was made on the patient's history, physical and

NUTRITIONAL ANEMIA IN AN INFANT RESPONDING TO PURIFIED LIVER EXTRACT

Macrocytic hyperchromic anemia in infancy is infrequently observed. Faber¹and Bachman²have reviewed 19 previously reported cases. Langmead and Doniach³recorded an additional case. Macrocytic hyperchromic anemia in infancy usually is observed in previously healthy infants after an infection of the upper respiratory tract followed by a period of vomiting or diarrhea or both. The patients are noticeably malnourished and fail to gain weight in spite of changes in formulas and addition of various vitamins to the diet. Free hydrochloric acid is nearly always present in the gastric contents, although frequently decreased in amount. Administration of crude liver extract by mouth or injection has frequently been followed by reticulocytosis, rapid rise in the number of red blood cells and gain in weight. Anemia does not recur after it has once been relieved. Because of the comparative rarity of this type of anemia, the case of a child

Macrocytic hyperchromic anemia of pregnancy

1.1. A case of a severe grade of macrocytic hyperchromic anemia induced by pregnancy is presented.2.2. It was recognized and successfully treated with hlood transfusion and parenteral liver therapy.3.3. A living male child was delivered spontaneously.4.4. A blood count of the child revealed no abnormalities.

Some Cases of macrocytic hyperchromic Anemia without Gastric Achylia, their Etiology and Relation to Cryptogenetic pernicious Anemia and to a New antianemic Factor

Some Cases of macrocytic hyperchromic Anemia without Gastric Achylia, their Etiology and Relation to Cryptogenetic pernicious Anemia and to a New antianemic Factor

Macrocytic hyperchromic anemia in children

Summary.The authors describe a case of macrocytic hyperchromic anemia in celiac disease in a girl of 8 1/2 years who, five years earlier, presented a clinical picture typical of celiac disease combined with anemia.A likely cause of the disease picture in this case is a paratyphoid infection incurred in early infancy (the first half of the second month). This paratyphoid fever (Breslau) was of long duration with positive bacillus findings in the feces for six months.

Effect of Parenteral Liver Extract on the Blood Picture of New Born Rats.

1. The transition from megaloblastic to normoblastic erythropoiesis appears to be reflected in data on the blood cell values of normal rats from birth to 24 days of age. 2. Blood cell values of young whose mothers were injected with liver extract before and during pregnancy were found to be not significantly different from control values at comparable ages after birth. 3. Blood cell values of young rats directly injected with liver extract up to the fourteenth day after birth were found not to be significantly different from control values at comparable ages after birth. 4. The young rat's reaction to the presence of excess anti-anemic principle resembles that of the human macrocytic hyperchromic anemia patient maintained on adequate amounts of liver extract.

MACROCYTIC HYPERCHROMIC ANEMIA IN EARLY INFANCY

During the past two decades exhaustive investigation has helped clarify many phases of the problem of infantile anemia. Deficiency and hemolytic anemia have been rather definitely differentiated, and each type in turn has been subdivided in an attempt to analyze further and to understand the pathogenesis involved. Investigations of microcytic hypochromic anemia have been comparatively thorough, probably because of its great frequency. On the other hand, the macrocytic hyperchromic type of deficiency anemia has been less completely studied, owing to its comparative rarity. In this paper a case of macrocytic hyperchromic anemia in an infant aged 9 months is reported, and the literature on similar anemia in patients under 1 year of age is reviewed. <h3>REVIEW OF THE LITERATURE</h3> Reports of cases of macrocytic hyperchromic anemia in early infancy have been scanty. Indeed, Blackfan,¹Cooley and Lee,²Naegeli³and others stated the belief that pernicious (Addison-Biermer's) anemia

Macrocytic Hyperchromic Anemia in Pregnancy : With The Report of a Case And A Review Of the Literature

Macrocytic Hyperchromic Anemia in Pregnancy : With The Report of a Case And A Review Of the Literature