What Causes Megaloblastic Anemia and How Is It Diagnosed?

What Causes Megaloblastic Anemia and How Is It Diagnosed?

“What causes megaloblastic anemia and how is it diagnosed?”

Megaloblastic anemia Pathology

Megaloblastic anemia is caused by impaired DNA synthesis and is characterized by the distinctive abnormality in the hemopoietic precursors in bone marrow in which maturation of the nucleus is delayed related to the cytoplasm. Defective DNA synthesis is due to a deficiency of vitamin B₁₂ and folic acid.

“Understanding megaloblastic anemia: Causes and diagnosis”

Megaloblastic anemia Etiology

1. Vitamin B₁₂ deficiency

• Inadequate dietary intake, For Example. Strict vegetarians, breastfed infants.
• Malabsorption

Gastric causes: Pernicious anemia, gastrectomy, congenital lack of intrinsic factor.

Intestinal causes: Tropical sprue, ileal resection, Crohn’s disease, intestinal blind loop syndrome, fish-tapeworm infestation.

Megaloblastic anemia

Causes of megaloblastic anemia

“Importance of diagnosing megaloblastic anemia early”

2. Folate deficiency

• Inadequate dietary intake, For Example. in alcoholics, teenagers, infants, old age, and poverty.
• Malabsorption, For Example. in tropical sprue, coeliac disease, partial gastrectomy, jejunal resection, and Crohn’s disease.
• Excess demand in
  • Physiological: pregnancy, lactation, infancy.
  • Pathological: malignancy, increased hematopoiesis, chronic exfoliative skin disorders, tuberculosis, rheumatoid arthritis.
• Excess urinary folate loss, For Example. in active liver disease and congestive heart failure.

“Treatment options for managing megaloblastic anemia”

3. Other causes

• Impaired metabolism, For Example. Inhibitors of dihydrofolate reductase such as methotrexate and pyrimethamine; alcohol, congenital enzyme deficiencies.
• Unknown etiology, For Example. in Di Guglielmo’s syndrome, congenital dyserythropoietic anemia, and refractory megaloblastic anemia.

Clinical Features And Causes Of Anemia Questions For Medical Exams

Laboratory Diagnosis of Megaloblastic Anemia

1. General Blood Parameters

• Decrease in RBC count and hemoglobin levels
• Increase in MCV and decrease in MCH.
• Reticulocyte count is normal

“Role of vitamin B12 injections in treating deficiency”

Diagnosis of megaloblastic anemia

2. Peripheral Smear

• Red cells show anisopokilocytosis with the presence of macrocytes and macro ovalocytes, i.e., large oval RBCs.
• Presence of Howell-Jolly bodies, i.e., nuclear remnants left after the nucleus is extruded and Cabot rings (abnormal histone synthesis causes arginine-rich histone to accumulate as rings in red cells)
• Neutrophil hypersegmentation is seen, i.e., greater than 5% of neutrophils with more than five lobes or the presence of at least one fixed lobe cell.

3. Bone Marrow Examination

• It shows megaloblastic hyperplasia. The nuclei of erythroblasts are large with fine and open sieve-like chromatin. Hemoglobinization of cytoplasm is of normal rate, while nuclear maturation lags behind that of cytoplasm. This is known as nuclear-cytoplasmic asynchrony.
• Giant metamyelocytes and stab form are seen.
• Megakaryocytes may be large and abnormal.

“Techniques for managing symptoms of megaloblastic anemia”

4. Biochemical Tests

• Serum vitamin B₁₂ levels less than 200 pg/ml are indicative of vitamin B₁₂ deficiency, and serum folate levels less than six ng/ml indicate folate deficiency. Two methods are used to measure serum B₁₂ microbiological and radioisotope assay. Radioisotope assay is the preferred method.
• Holotranscobalamin is considered active B₁₂ and is the earliest biomarker for vitamin B₁₂ deficiency.
• Elevated methylmalonic acid level indicates a depletion of vitamin B₁₂ stores.
• Isolated decreased levels of holo transcobalamin support vitamin B₁₂ deficiency, and a combination of decreased Holotranscobalamin and increased methylmalonic acid
  and homocysteine indicate a metabolically manifest B₁₂ deficiency.
• Schilling test: It is useful for diagnosing intrinsic factor deficiency. It measures the absorption of free radiolabelled vitamin B₁₂.
• Radiolabelled vitamin B₁₂ is given orally, followed in 1 to 6 hours by 1000 mg of parenteral vitamin B12, which reduces the uptake of radiolabelled vitamin B₁₂ by the liver.
• Absorbed radiolabelled vitamin B12 is excreted in the urine, which is collected for 24 hours. The amount excreted is measured, and the percentage of radiolabelled vitamin B₁₂ is determined.
• If absorption is normal, i.e.,≥ 9% of the dose given appears in the urine. Reduced urinary excretion (if kidney function is normal) indicates inadequate vitamin B₁₂ absorption.

Vitamin B12 deficiency anemia

“Pathophysiology of megaloblastic anemia explained”

“Emerging research on megaloblastic anemia treatments”

Megaloblastic Anemia

Classification of Morphological Anemia

Based on red cell size, hemoglobin content, and red cell indices.

Microcytic hypochromic: MCV, MCH, and MCHC are all reduced For Example. in iron deficiency anemia and certain non-iron deficiency anemias, i.e., sideroblastic anemia, thalassemia, and anemia of chronic disorders.

Normocytic normochromic: MCV, MCH, and MCHC are all normal, For Example. after acute blood loss, hemolytic anemias, bone marrow failure, and anemia of chronic disorders.

Macrocytic: MCV is raised, For Example. in megaloblastic anemia due to a deficiency of vitamin B₁₂ and folic acid.

“Global prevalence of megaloblastic anemia based on lab data”

Question 2. Describe in brief peripheral and bone marrow pictures of megaloblastic anemia.
Answer:

• Peripheral picture
  • Red cells show anisopokilo cytosis with the presence of macrocytes and macro ovalocytes, i.e., large oval RBCs.
  • Presence of Howell-Jolly bodies, i.e., Nuclear remnants left after the nucleus is extruded and Cabot rings (abnormal histone synthesis causes arginine-rich histone to accumulate as rings in red cells)
  • Neutrophil hypersegmentation is seen, i.,e. greater than 5% of neutrophils with more than five lobes or the presence of at least one six-lobe cell.

“Case studies on outcomes of megaloblastic anemia management”

• Bone marrow picture
  • It shows megaloblastic hyperplasia. The nuclei of erythroblasts are large with fine and open sieve-like chromatin. Hemoglobinization of cytoplasm is of normal rate, while nuclear maturation lags behind that of cytoplasm. This is known as nuclear-cytoplasmic asynchrony.
  • Giant metamyelocytes and stab form are seen.
  • Megakaryocytes may be large and abnormal.