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megaloblastic anemia peripheral smear macro ovalocytes hypersegmented neutrophils B12 deficiency professional reference

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megaloblastic anemia

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1. Interpretation of the complete blood count

This is severe macrocytic megaloblastic anemia, most likely due to vitamin B12 deficiency, with associated mild leukopenia and thrombocytopenia.
FindingInterpretation
Hb 7.4 g/dL, RBC 2.69 million/µLSevere anemia
MCV 118 fLMacrocytosis
MCH 39.6 pgRaised because RBCs are large
MCHC 33.7 g/dLNormal chromia
RDW 18%Increased variation in RBC size, anisocytosis
Reticulocytes 0.4%Inadequate marrow response, underproduction anemia
TLC 3,400/µLLeukopenia
Platelets 100,000/µLThrombocytopenia
Vitamin B12 150 pg/mLLow, supports vitamin B12 deficiency
Thus, there is ineffective hematopoiesis causing pancytopenia: anemia, leukopenia, and thrombocytopenia. The classic smear findings and reticulocytopenia support megaloblastic anemia. Merck Manual review

2. What is MCV? What does an MCV of 118 fL indicate?

MCV, or mean corpuscular volume, is the average volume or size of a red blood cell.
  • Normal: approximately 80-100 femtolitres (fL)
  • This patient: 118 fL
An MCV of 118 fL indicates macrocytosis, meaning enlarged red blood cells. In this case, marked macrocytosis with low B12 strongly points to megaloblastic anemia due to vitamin B12 deficiency.

3. Peripheral blood smear findings in megaloblastic anemia

Expected smear features are:
  • Macro-ovalocytes: large, oval-shaped RBCs
  • Anisocytosis: marked variation in RBC size
  • Poikilocytosis: variation in RBC shape, sometimes including teardrop forms
  • Hypersegmented neutrophils
  • May show Howell-Jolly bodies
  • Reduced platelets, sometimes large platelets
  • Leukopenia and thrombocytopenia may be present in severe disease
Textbook findings describe oval macrocytes and hypersegmented neutrophils as typical of B12 or folate deficiency. Frameworks for Internal Medicine, “Macrocytic Anemia,” lines 7471-7484.

4. What is a hypersegmented neutrophil?

A hypersegmented neutrophil is a neutrophil with abnormally excessive nuclear lobulation.
Definition:
  • A neutrophil with 6 or more nuclear lobes, or
  • Increased proportion of neutrophils having 5 lobes
It results from impaired DNA synthesis and delayed nuclear maturation. It is a characteristic feature of megaloblastic anemia, especially due to vitamin B12 or folate deficiency.

5. Why is the reticulocyte count low?

Reticulocytes are newly produced immature RBCs. Their count should rise when the marrow responds appropriately to anemia, as in acute blood loss or hemolysis.
Here, the reticulocyte count is low because vitamin B12 deficiency causes:
  1. Defective DNA synthesis in erythroid precursors.
  2. Failure of normal nuclear maturation, producing megaloblasts.
  3. Ineffective erythropoiesis: many abnormal developing RBC precursors die within the bone marrow before entering the circulation.
  4. Therefore, the marrow cannot mount an adequate reticulocyte response despite severe anemia.

6. Why are total leukocyte count and platelet count also reduced?

Vitamin B12 deficiency impairs DNA synthesis in all rapidly dividing bone-marrow cells, not just erythroid cells.
Therefore, there is ineffective maturation and increased intramedullary death of:
  • Erythroid precursors: anemia
  • Myeloid precursors: leukopenia, sometimes neutropenia
  • Megakaryocytic precursors: thrombocytopenia
This produces pancytopenia in severe megaloblastic anemia. Frameworks for Internal Medicine, “Macrocytic Anemia,” lines 7445-7470.
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