Macrocytic anemia: Pathology review

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Macrocytic anemia: Pathology review



Macrocytic anemia: Pathology review

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A 16-month-old boy is brought by his parents to the pediatrician’s office to establish care. The patient’s family recently immigrated from Eastern Europe, and medical records are not available. The mother notes that the patient has not been growing as quickly as his siblings grew. In the office, the patient’s temperature is 37.5°C (99.5°F), blood pressure is 105/62 mmHg, pulse is 100/min, and respirations are 28/min. Physical exam reveals hyperpigmented spots on the patient’s body and hypoplastic thumbs. The patient’s height, weight, and head circumference are below the 3rd percentile. Laboratory testing reveals the following results:  
 Laboratory value  Result 
 Hemoglobin  8.1 g/dL 
 Leukocyte  2,300/mm3 
 Platelet  65,000/mm3 
 Mean Corpuscular Volume  109 mm3 
The patient’s condition is most likely due to a defect involving which of the following processes?


In the hematology ward, two people came in with the same symptoms: easy fatigability, exertional dyspnea, and weight loss. One of them is a 65 year old caucasian individual named Bobby, and the other one is a 50 year old Hispanic individual named Sara. Bobby complains of frequent falls, while Sara admits she is a chronic user of alcohol. Their lab tests show decreased hemoglobin levels.

Both Bobby and Sara are suffering from anemia, which is defined as lower than average levels of hemoglobin, typically below 13.5 g/dL in adult men and below 12.0 g/dL in adult women. Now, anemias can be broadly grouped into 3 categories based on mean corpuscular volume, or MCV, which reflects the volume of a Red Blood Cell or RBC. So microcytic anemia is where the MCV is lower than 80 fL, normocytic, with an MCV between 80 and 100 fL, and macrocytic, with an MCV larger than 100 fL. Now, let’s focus on the macrocytic anemias. The two most common causes are vitamin B12 deficiency and folate deficiency. Orotic aciduria, Fanconi anemia, Diamond-Blackfan anemia are also macrocytic. Finally, liver diseases and hypothyroidism can also cause this type of anemia, but their mechanisms are not well understood.

Okay! Macrocytic anemias can be classified based on the presence of megaloblasts. These are large, immature red blood cells produced when the cytoplasm develops normally, but the DNA synthesis is impaired and cell division is delayed. So when there’s defective DNA synthesis or defective DNA repair like in folate deficiency, vitamin B12 deficiency, orotic aciduria, and Fanconi anemia there’s megaloblastic macrocytic anemia. Megaloblastic anemia can also affect white blood cell production, so the bone marrow starts releasing large, immature neutrophils, with hypersegmented nuclei, meaning their nucleus has more than 5 lobes. These are called hypersegmented neutrophils and are a key finding on the peripheral blood smear of individuals suffering from megaloblastic anemia.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pernicious Anemia" New England Journal of Medicine (1997)
  4. "Megaloblastic Anemias" Medical Clinics of North America (2017)
  5. "Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families" Am J Hum Genet (1997)
  6. "Why does the bone marrow fail in Fanconi anemia?" Blood (2014)
  7. "Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference" British Journal of Haematology (2008)

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