Megaloblastic Anemia Research Articles

Etiology and Pathogenesis of Macrocytic Anemia

Anemia is the most common conditions detected by primary care doctors in Indonesia and worldwide. In 2010, the global prevalence of anemia was 32.9%; that is, more than 2.2 billion people have anemia in the world. Macrocytic anemia refers to a condition that refers to macrocytosis, or when the mean corpuscular volume (MCV) is greater than 100 fL in moderate anemia, the hemoglobin is less than 12 g/dL, or the hematocrit is less than 36%. To identify the etiology and course of the disease in macrocytic anemia. This writing uses the method of studying the relevant literature related to the etiology and course of the disease, macrocytic anemia. The search engines used in this paper include Pubmed, Google Scholar, Research Gate, NCBI, and BMC. This article uses 22 articles that were used as references in its preparation. Megaloblastic anemia has etiologies in the form of vitamin B12 and folate deficiency, while non-megaloblastic anemia has etiologies such as alcohol consumption, MDS, hyperthyroidism, etc. The disease course of the two types of macrocytic anemia also differs based on the type, namely megaloblastic and non-megaloblastic. In general, macrocytic anemia is divided into megaloblastic anemia and non-megaloblastic anemia; these divisions have different etiologies dan pathogenesis.

Evaluation of pancytopenia based on bone marrow examination in adults in a tertiary care hospital in Islamabad.

Objective: To evaluate etiological spectrum of pancytopenia in adults using bone marrow aspiration biopsy. Study Design: Randomized Prospective study. Setting: Department of Pathology, Pakistan Institute of Medical Sciences, Islamabad. Period: October 2018-October 2020. Material & Methods: Eight hundred bone marrow biopsies were performed out of which 250 patients came with pancytopenia. 135 patients out of these were in adult age group which are included in this study. Results: Out of 250 patients adults were 135 that presented with pancytopenia. Male to female ratio came out to be 1.22:1. The most common disorder that results in pancytopenia came out to be megaloblastic anemia that was 29.6%, after that 26.6% were infection related changes, 10.3% aplasia, 9.6% reactive marrow, 5.9% acute leukemia, 3.7% chronic leukemia and iron deficiency anemia followed by 2.9% myelodysplastic syndromes and hypersplenism, 2.2% multiple myeloma, 1.4% mixed deficiency anemia and 0.74% myelofibrosis. We also analyzed patients on their presenting complaints as well. Most common complaint of presentation was fever (54.8%), (31.85%) with fatigue and malaise, (31.1%) pallor, vomiting and diarrhea (25.9%) followed by bleeding (14.8%). On clinical examination 12% cases presented with hepatomegaly and 16.6% with splenomegaly. Conclusion: Pancytopenia is a common hematological finding in our setup with megaloblastic anemia to be the most common cause of it. Therefore, it’s very important to diagnose it as this is a curable (reversible) deficiency and patients can easily be managed to prevent serious hematological and neurological abnormalities.

Thiamine-Responsive Megaloblastic Anemia Syndrome Combined with Thalassemia Trait: A Rare Association

Abstract Introduction Thiamine-responsive megaloblastic anemia syndrome (TRMA, OMIM reference 249270), also known as Rogers' syndrome, is a rare type of anemia characterized by the triad megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus (DM). Disturbance of thiamine transport into cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. Case Report We report the case of an 8-year-old girl who presented at age 4 years with anemia. She had a combined hematological profile of microcytic and macrocytic anemia. The parents refused bone marrow aspiration and genetic diagnosis. Hemoglobin electrophoresis established the thalassemia trait. She was later confirmed to have sensorineural deafness and monogenic DM. A tentative TRMA diagnosis was based on megaloblastic anemia, sensorineural deafness, and monogenic DM triad. The patient was treated empirically with a daily dose of thiamine 200 mg; her hemoglobin level normalized, but the deafness and DM did not improve. Conclusion In routine practice, patients with TRMA must be evaluated thoroughly for other causes of megaloblastic anemia, including therapeutic thiamine trials in the presence of sensorineural deafness or DM. These patients should be followed throughout their life span both for DM and to control their response to thiamine therapy for megaloblastic anemia.

FRET-based probe for ratiometric detection and imaging of folic acid in real-time

Inadequate folic acid intake is linked to diseases such as megaloblastic anemia, neural tube defects, and hyperhomocysteinemia, increasing the risk of vascular disease and thrombosis. Folic acid, a cofactor in various enzymes, can be produced by plants and bacteria, but not by humans and other animals. L-5-methyl-tetrahydrofolate (L-5-methyl-THF) is the primary dietary folate form, transported in circulation for cellular metabolism. Traditional methods of determining folic acid levels are unreliable and time-consuming. SenFol (Sensor for folic acid) is a fluorescence resonance energy transfer (FRET)-based nanosensor that we have developed by inserting folic acid-binding protein (FolT) as the folate detecting domain between the pair of enhanced cyan fluorescent protein (ECFP) and Venus. The developed sensor is highly specific, produces a quick signal, which is pH stable, and delivers precise, ratiometric readings in cell-based experiments. The projected affinity score of folic acid with FolT was −7.4 kcal/mol. The apparent affinity (Kd) of SenFol for folic acid is 28.49 × 10−9 M, with a detection range of 5 × 10−9 M to 5 × 10−7 M, and a maximum FRET ratio change of 0.45. WT SenFol, a highly efficient folic acid nanosensor, can dynamically detect intracellular folic acid content in E. coli, yeast, and HEK-293 T cells, confirming its potential.

Etiological Profile of Macrocytic Anemia in Patients Attending a Tertiary Care Hospital in Nepal

Introduction: The morphological classification of anemia often correlates with the cause of red cell deficiency. Megaloblastic and non-megaloblastic macrocytic anemias are important causes of anemia in at least 1.7% of hospital patients. Vitamin B12 and folate deficiency are rampant in underdeveloped countries. In Nepal, there is a lack of local data evaluating the etiological profile of macrocytic anemia. Methods: A descriptive hospital-based study was conducted, and thirty-five cases of anemia according to the WHO criteria were included after informed consent. Clinical history, physical examination, complete hemogram (including hemoglobin level, red cell indices, total leucocyte count, platelet count, and reticulocyte count), and a peripheral blood smear were obtained per structured proforma. Appropriate biochemical investigations were acquired. Statistical analyses were performed as per standard statistical protocols. Results: The mean age of the patients in our study was 42.40 (±10.29) years. There was a slight male predominance (n=20; 57.14%). Most cases (n=27;77.14%) of macrocytic anemia were megaloblastic. Vitamin B12 deficiency (n=13; 48.14%) was the commonest identifiable cause in megaloblastic group, while liver disease accounts for half of the cases (n=4; 50%) of non-megaloblastic group. The mean hemoglobin was lower (9.94±1.43 g/dl) in megaloblastic anemia compared to non-megaloblastic macrocytic anemia (10.96±1.24 g/dl). Conclusion: The present study showed that megaloblastic anemia was the most common cause of macrocytic anemia, primarily due to vitamin B12 and folate deficiency. Non-megaloblastic anemia was mainly attributed to liver diseases.

Computational analysis of peripheral blood smears detects disease-associated cytomorphologies

Many hematological diseases are characterized by altered abundance and morphology of blood cells and their progenitors. Myelodysplastic syndromes (MDS), for example, are a group of blood cancers characterised by cytopenias, dysplasia of hematopoietic cells and blast expansion. Examination of peripheral blood slides (PBS) in MDS often reveals changes such as abnormal granulocyte lobulation or granularity and altered red blood cell (RBC) morphology; however, some of these features are shared with conditions such as haematinic deficiency anemias. Definitive diagnosis of MDS requires expert cytomorphology analysis of bone marrow smears and complementary information such as blood counts, karyotype and molecular genetics testing. Here, we present Haemorasis, a computational method that detects and characterizes white blood cells (WBC) and RBC in PBS. Applied to over 300 individuals with different conditions (SF3B1-mutant and SF3B1-wildtype MDS, megaloblastic anemia, and iron deficiency anemia), Haemorasis detected over half a million WBC and millions of RBC and characterized their morphology. These large sets of cell morphologies can be used in diagnosis and disease subtyping, while identifying novel associations between computational morphotypes and disease. We find that hypolobulated neutrophils and large RBC are characteristic of SF3B1-mutant MDS. Additionally, while prevalent in both iron deficiency and megaloblastic anemia, hyperlobulated neutrophils are larger in the latter. By integrating cytomorphological features using machine learning, Haemorasis was able to distinguish SF3B1-mutant MDS from other MDS using cytomorphology and blood counts alone, with high predictive performance. We validate our findings externally, showing that they generalize to other centers and scanners. Collectively, our work reveals the potential for the large-scale incorporation of automated cytomorphology into routine diagnostic workflows.

Significance of Reticulocyte Count in Assessment of Pancytopenia at Tertiary Care Hospital

Aim: To determine the significance of reticulocyte count in assessment of pancytopenia. Study Design: Retrospective study Place and Duration: Department of Pathology, Diagnostic and research Laboratory LUMHS, Hyderabad. Jan 2017-Oct 2018. Methods: The study comprised a total of one hundred pancytopneia patients. The comprehensive demographics of the enrolled cases were collected upon obtaining informed written consent. The diagnostic utility of absolute reticulocyte count was determined by correlating it with bone marrow biopsy. SPSS 22.0 was used to analyze the data. Results: Among all, 43% were males and 57% were females. Age of the presented cases was 35.3±2.54 years. 62% patients were married and 37% cases were literate. Majority 59% patients were from rural areas. Megaloblastic anemia was the most common etiology found in 52% cases with reticulocyte count 0.2%, aplastic anemia in 22% cases with reticulocyte count 0.1%, mixed deficiency anemia in 17% reticulocyte count 0.4%, acute leukemia in 6% with reticulocyte count 0.7% and 3% cases had myelodysplastic syndrome with reticulocyte count 0.2%. The most frequent clinical features that were present were pallor (88%), generalized weakness (81%), dyspnea (62%), and fever (60%). Conclusion: Reticulocyte count plays an important role in differentiating various causes of pancytopenia and hence should be routinely included in pancytopenia work up in order to avoid unnecessary bone marrow aspirations. Keywords: Pancytopneia, Reticulocyte count, Fever, Pallor, Biopsy

Screening of antenatal patients for anaemia and haemoglobinopathies

Introduction: Anaemia is an extremely common condition in pregnancy worldwide, conferring a number of health risks to mother and child. Iron deficiency is most widespread micronutritional deficiency in the world and disproportionately affects female because of increased iron requirements during menstruation, pregnancy and lactation. Haemoglobinopathies are a group of inherited disorders because of abnormalities in haemoglobin synthesis or structure. Thalassemia and Sickle cell anaemias are the most prevalent haemoglobinopathies and a national health burden in India so identifying these disorders during antenatal period is necessary to take appropriate measures. Methods: A prospective study of screening for haemoglobin variants in Antenatal Patients due to low haemoglobin and evaluation of other causes was performed for 1 year with 570 samples. In Low Hb patients’ CBC, Reticulocyte staining and sickling test was performed. Haemoglobin analysis was done by HPLC BIO RAD VARIANT II. In Iron Deficiency Anaemia (IDA) Serum ferritin & Serum Iron level were done and in Megaloblastic Anaemia(MA) Vitamin B12 level were done. Result: Prevalence of anaemia in antenatal patients was 90.25%; in this IDA presented with 84.21%, MA with 4.73% and Dimorphic anaemia 1.27%. Prevalence of haemoglobinopathies in this study was 9.75%; in this Beta Thalassemia Minor present with 5.08%, Sickle Cell Trait 4.03%, Hb D Punjab 0.52% and Hb Q india 0.17%. Conclusion: Antenatal screening for genetic disorders, such as Beta thalassemia, Sickle Cell Anaemia, aims to reduce the burden of these diseases by offering information to individual with a high likelihood of giving birth to affected babies and giving parents more choices regarding their reproductive decisions. For this, premarital and antenatal screening should be mandatory to prevent the birth of affected offspring.

Study of the Aetiology and Clinical Manifestations of Thrombocytopenia in a Tertiary Care Centre.

Introduction Thrombocytopenia is a commonly observed condition in clinical practice, and its diagnosis is often challenging due to numerous aetiologies and variations in clinical presentation. Early identification of thrombocytopenia and its causes can help prevent life-threatening haemorrhagic manifestations. Methodology A prospective observational study was conducted at a tertiary care hospital from February 2019 to January 2020. This evaluation aimed to determine the causes and prevalence of thrombocytopenia in a tertiary care setting. Patients aged 15 or older with a platelet count of fewer than 150,000/ µL were eligible for inclusion in this evaluation. Investigations for aetiology detection were recommended. Results During the one-year study period, a total of 100 patients, including 58 males and 42 females, with thrombocytopenia were selected for the study. The most common age group affected by thrombocytopenia in this study was between 46 and 55 years old. The most common clinical manifestations observed were generalised weakness (70%), haemorrhagic manifestations (60%), fever (50%), joint pain (37%), splenomegaly (35%), headache (30%), breathlessness (23%), lymphadenopathy (22%), hepatomegaly (24%), and abdominal pain (12%). The most prevalent causes of thrombocytopenia were megaloblastic anaemia (19 cases), dengue fever (15 cases), malaria (11 cases), enteric fever (nine cases), immune thrombocytopenia (ITP) (eight cases), and leukaemia (seven cases). Bleeding was reported as a symptom of thrombocytopenia in 60% of individuals in this study. Conclusion In the study, thrombocytopenia was more common in people aged 46-55 years, and males were more commonly affected than females. Megaloblastic anaemia and infectious disease were the most common causes of thrombocytopenia. Bleeding manifestations were found in 60% of patients with thrombocytopenia.

Essential thrombocythemia masked by vitamin B 12 deficiency megaloblastic anemia: A case report

The association of megaloblastic vitamin B12 deficiency anemia and essential thrombocythemia is very rarely described in the literature. We reported a case of a 65-year-old patient with an isolated chronic anemic syndrome secondary to megaloblastic vitamin B12 deficiency anemia treated with vitamin B12 therapy by injection. The evolution was marked three months after treatment by the an ischemic cerebrovascular accident and thrombocytosis. Additional investigations confirmed essential thrombocythemia. The patient was put under hydroxyuria and an anticoagulant treatment with a good evolution.

FREQUENCY OF CAUSES OF PANCYTOPENIA IN BONE MARROW SAMPLES OF PATIENTS

Objective: The aim of this study is to find out the common causes that lead to pancytopenia in our population specially in the province of Punjab. Material and Methods: This is a cross sectional study that was conducted at Chughtai Institute of Pathology, Lahore. The duration of the study was from June 2020 to December 2021. A total of 210 patients were included in the study. A through history was taken and complete physical examination was done prior to the bone marrow biopsy procedure. Peripheral blood sample was run on Sysmex XN 9000 automated hematology analyzer. Bone marrow aspirate and trephine biopsy were thoroughly examined and immunohistochemical stains were applied where required. The data was analyzed using SPSS 23.0 and frequencies were calculated. Results: Most common causes of pancytopenia in our study were megaloblastic anemia (18.1%) followed by aplastic anemia (12.9%), immune mediated causes (12.4%), acute myeloid leukemia (11%), hypocellular marrow (9%) myelodysplastic syndrome (6.2%), hypersplenism (5.2%) and Precursor B acute lymphoblastic leukemia (5.2%) (Fig. 2). Other causes include B cell non-Hodgkin lymphoma (4.8%), mixed deficiency anemia (4.2%), hypersplenism (3.8%), Gaucher’s disease (1.4%), infections (1%) and other miscellaneous causes (4.8%). Conclusion: The study conducted at our institute showed that majority of patients had benign causes (69.2%) leading to pancytopenia, the most common cause being megaloblastic anemia. Malignant causes constitute only a minority of cases of pancytopenia. Key Words: Bone marrow biopsy, Frequency, Pancytopenia

Early treatment of subacute combined degeneration of the spinal cord in pernicious anemia will improve the outcome

Vitamin B12 deficiency is probably more common than what is reported in the literature. B12 is an essential vitamin, and its deficiency can lead to neuropsychiatric manifestations such as peripheral neuropathy, myelopathy, cerebellar ataxia, dementia, delirium, even psychosis and mood disorders. We report a case of 45 year old polish male presented with symptoms and signs suggestive of SCD of the spinal cord, due to severe vitamin B12 deficiency as a result of pernicious anemia. Cervical spine MRI showed enhancement in the bilateral posterior columns of the cervical spinal cord with a classic inverted V appearance. Metabolic workup revealed severe vitamin B12 deficiency, complete blood analysis indicated megaloblastic anemia. Intramuscular injection of cobalamin was started on a timely manner with complete resolution of symptoms.

EFFECT OF FOLIC ACID ON SOME PHYSIOLOGICAL PARAMETERS IN FEMALE RABBITS TREATED WITH METHOTREXATE

The present study was carried out to investigate the effect of folic acid (FA) on the hematological picture of female rabbits treated with methotrexate MTX. A total of twenty female rabbits were used in this study. They were at age 4-5 months. Their body weight ranged between 1-1,200 Kgm. All animals were kept under normal condition. its divided in to four groups and each group consist of five animals as follows ( Control group :5 rabbits were received distilled water, Folic acid group : 5 rabbits were received folic acid at 0.07mg/kg body weight daily, Methotrexate group : 5 rabbits were received methtrexate (0.03 mg/kg body weight ) three times a week , folic acid with Methotrexate group : 5 rabbits were received folic acid (0.07 mg/kg body weight) and methotrexate (0.03mg/kg body weight) three times a week. The drugs were given by intubation. The experiment was last for 9 weeks . Blood sample were collected after end of the experiment to study the following hematological parameters: RBCs count, Hb, PCV, RBCs indices (MCV, MCH, MCHC). The group treated with folic acid showed a significant increase P≤0.05 in RBCs count, Hb conc. and PCV% as compared with all other groups. The results of MTX group reveal a high significant decrease in their RBC count, Hb conc., PCV%. At the same time there is a significant increase in MCV, MCH and MCHC indices. The group of animals received FA with MTX showed a good prognosis with health improvement characterized by high significant changes in all studied parameters to return back to their normal values. It was concluded that folic acid is very important for erythropoiesis. MTX treatment induce megaloblastic anemia resulted from inhibition of DNA synthesis in RBCs mainly by folate deficiency. FA administration with MTX correct these changes and the animals return to normal conditions. More work is needed to study the effects of these drugs on other systems in the body.

A Brief Review on the Association of Prolonged Metformin Therapy and Vitamin B12 Deficiency

Type 2 Diabetes Mellitus is a fast-growing health challenge, signaled by hyperglycemia. There are two types of diabetes mellitus, Type 1 and Type 2; both are equally life threatening condition. Type 1 diabetes is a persistent autoimmune disease as a consequence of insulin deficiency, whereas in Type 2 diabetes the body either does not produce enough insulin or develops resistance to insulin. Metformin is the exclusive pharmacologic management for Type 2 diabetes mellitus and frequently prescribed drug either single or in combination with insulin or other hypoglycemic agents. Metformin has immensely improved insulin sensitivity and defend against vascular complications. Vitamin B 12 (cobalamin) has a vital role in DNA synthesis, cellular metabolism and the deficiency will lead to megaloblastic anemia. Several studies state that metformin can cause cobalamin deficiency in doses greater than 2000 mg/ day and for a time period of more than 4 years. Hence, cobalamin and calcium supplementation will reduce the occurrence of cobalamin deficiency in patients with metformin therapy. Keywords: Type 2 diabetes mellitus, Metformin, Vitamin B 12, Vitamin B 12 deficiency, Cobalamin.

The Intake of Junk Food as an Etiological Factor of Megaloblastic Anemia in Patients visiting Mayo Hospital, Lahore

Objective: The study was performed to determine role of junk food intake in the development of megaloblastic anemia.
 Methodology: It was a clinical based cross-sectional study conducted at Mayo Hospital Lahore in collaboration with Pathology Department of King Edward Medical University from June 2017 to June 2021. All the patients of age 7 to 70 years including males and non-pregnant females attending the Out Patient Department or admitted in the hospital and having hemoglobin values<12 gm/l, MCV more than 95 fl and bone marrow examination suggestive of a megaloblastic change in the marrow (WHO criteria)were included in our study. The patients who had received blood transfusion or hematinic in less than 6 months before diagnosis and pregnant females were excluded from our study. A total 1333 patients were screened, out of which only 160 patients were diagnosed with megaloblastic anemia who had undergone bone marrow trephine biopsy. Their dietary history was taken in detail and history of depression was noted on validated questionnaires. The obtained data was analyzed on the basis of age groups (7-25 years, 26-50 years, 51-75 years) using SPSS descriptive analysis and results were formulated.
 Results: The study revealed that 160 (12%) of total 1333 patients were diagnosed with megaloblastic anemia on bone marrow trephine biopsy with male to female ratio of 1:1.28. Total 58 (36%) patients belonged to 1-25 years age group 68 (43%) patients to 26-50 years age group and 34 (21%) patients belonged to 51-75 years age group. Junk food consumption was seen (60.3%) in 7-25 years age group as a prevalent etiological factor.
 Conclusion: Junk food consumption is the major cause of megaloblastic anemia in young population and poor diet in middle age group, whereas comorbidities are the major etiological factor in older people.

Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia

Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.

CD36 relative mean fluorescence intensity of CD105+ nucleated erythroid cells can be used to differentiate myelodysplastic syndrome from megaloblastic anemia

This study aims to evaluate the differences in CD105+ nucleated erythroid cell (NEC) immunophenotypes between myelodysplastic syndrome (MDS) and megaloblastic anemia (MA) using multiparameter flow cytometry and to screen potential markers. We analyzed bone marrow sample data from 37 patients with MDS, 35 with MA, 53 with iron-deficiency anemia (anemic controls), and 35 without anemia (normal controls). Compared with normal controls, the MDS and MA groups showed a decrease in the proportion of CD117+CD105+NEC and the relative mean fluorescence intensity (RMFI) of CD71 in CD105+NEC, accompanied by an increase in the coefficient of variation (CV) of CD71 and CD36. Additionally, CD36 RMFI of CD105+NEC increased in the MA group. Compared with anemia controls, the MDS and MA groups showed a significant increase in CD36 CV of CD105+NEC, and the CD36 RMFI in the MA group increased while that in the MDS group decreased. The proportions of CD117+CD105+NEC, CD36 CV, and CD36 RMFI in CD105+NEC differed significantly between MDS and MA groups. Among them, CD36 RMFI had good diagnostic performance (area under the curve: 0.844, 95% confidence interval: 0.753–0.935). CD36 RMFI of CD105+NEC may be a helpful marker in differentiating MDS and MA using multiparameter flow cytometry.

Causes of Abnormal Hemoglobin Electrophoresis

To investigate the possible causes of abnormal hemoglobin electrophoresis results. The hemoglobin electrophoresis results of 5 696 patients in the First Affiliated Hospital of Chengdu Medical College from September 2018 to July 2021 were collected, and the abnormal results and clinical significance were analyzed. The results of 486 patients (accounting for 8.53%) were abnormal, of which 300 cases had increased HbA2, 135 cases had decreased HbA2, 44 cases had increased F alone, and 7 cases had abnormal hemoglobin bands. Among the 486 patients, 246 patients were thalassemia gene positive (the positive rate was 50.62%), including 29 cases of α thalassemia, 208 cases of β thalassemia and 9 cases of αβ thalassemia. Among the patients with elevated HbA2, 68.67% were detected β thalassemia, 3.00% αβ thalassemia, 9.33% were suspected to be caused by macrocytosis, 6.33% by thyroid dysfunction, and 12.67% by uncertainty of the method. Among the patients with reduced HbA2, 21.48% were detected α thalassemia, 60.00% iron deficiency anemia, 8.15% were suspected to be caused by thyroid dysfunction, and 10.37% by uncertainty of the method. Among the patients with elevated F alone, the results of thalassemia gene detection were negative, 40.91% of them were suspected to be caused by macrocytosis, 27.27% by hereditary persistence of fetal hemoglobin, 29.55% by special physiological condition of pregnant women, and 2.27% by hyperthyroidism. Abnormal hemoglobin bands were detected in 7 patients, including 4 cases of hemoglobin D, 2 cases of hemoglobin E, and 1 case of hemoglobin J. Thalassemia, iron deficiency anemia, macrocytosis such as megaloblastic anemia and non-severe aplastic anemia, thyroid dysfunction, hereditary persistence of fetal hemoglobin, abnormal hemoglobin diseases, the uncertainty of the method are all important causes of abnormal hemoglobin electrophoresis results. In clinical work, the patient's indicators should be comprehensively analyzed to determine the possible cause.

Clinical Pathobiochemistry of Vitamin B12 Deficiency: Improving Our Understanding by Exploring Novel Mechanisms with a Focus on Diabetic Neuropathy.

Vitamin B12 (B12) is an essential cofactor of two important biochemical pathways, the degradation of methylmalonic acid and the synthesis of methionine from homocysteine. Methionine is an important donor of methyl groups for numerous biochemical reactions, including DNA synthesis and gene regulation. Besides hematological abnormalities (megaloblastic anemia or even pancytopenia), a deficiency in B12 may cause neurological symptoms, including symptoms resembling diabetic neuropathy. Although extensively studied, the underlining molecular mechanism for the development of diabetic peripheral neuropathy (DPN) is still unclear. Most studies have found a contribution of oxidative stress in the development of DPN. Detailed immunohistochemical investigations in sural nerve biopsies obtained from diabetic patients with DPN point to an activation of inflammatory pathways induced via elevated advanced glycation end products (AGE), ultimately resulting in increased oxidative stress. Similar results have been found in patients with B12 deficiency, indicating that the observed neural changes in patients with DPN might be caused by cellular B12 deficiency. Since novel results show that B12 exerts intrinsic antioxidative activity in vitro and in vivo, B12 may act as an intracellular, particularly as an intramitochondrial, antioxidant, independent from its classical, well-known cofactor function. These novel findings may provide a rationale for the use of B12 for the treatment of DPN, even in subclinical early states.

Fever with Thrombocytopenia in the Pediatric Age Group

Introduction: Fever with thrombocytopenia refers to a reduction in platelet count below 150,000/L in association with fever. Although febrile thrombocytopenia may occur due to aplastic anemia, malignancy or megaloblastic anemia, its commonest cause in the pediatric age group is infections like Dengue fever, Malaria and Enteric fever. Since infectious diseases are highly prevalent in our region we decided to determine the frequency of diseases associated with febrile thrombocytopenia in the pediatric age group. Objective: To determine the frequency of diseases associated with febrile thrombocytopenia in the pediatrics age group Study Design: Descriptive Cross-Sectional Study Place and Duration: Department of Paediatric Medicine, Civil Hospital, Karachi, Pakistan from November 22, 2018, to May 21, 2019 Methodology: After obtaining informed consent data related to signs, symptoms, clinical and confirmed diagnosis, and relevant lab results were recorded for children who fulfilled the inclusion criteria. Data were analyzed in terms of frequencies and percentages for qualitative variables like age group, gender and outcome variables. Results: Mean ± SD of age was 4.74±3.28. Out of 89 patients, 45(50.56%) were male and 44(49.44%) were female. In distribution for common causes of thrombocytopenia, 19 (21.3%) had malaria, 8 (9%) had dengue, 25 (28.1%) had an enteric fever, 32 (36%) had sepsis, 2 (2.2%) had malignancy and 3 (3.4%) had megaloblastic anemia. Conclusion: Sepsis, dengue, and malaria were the most frequent causes of thrombocytopenia. Therefore, anytime thrombocytopenia is found, more investigations can usually assist us in making the right diagnosis. Keywords: Febrile Thrombocytopenia, Malaria, Sepsis, Dengue, Enteric.