Macrocytic anemias characterized by increase in average RBC size and proportional Hb increase. Peripheral blood smear shows increased RBC thickness and loss of central pallor.

Megaloblastic anemias are associated with changes in perpheral RBCs and bone marrow cells related to impairment of DNA synthesis. All megaloblastic anemias are macrocytic but not all macrocytic anemias are megaloblastic.

Megaloblastic anemias

- Key findings and features (Blood and BM smears)

Peripheral blood smear:

- Hypersegmented neutrophils

- macroovalocytes

- fragmented cells

- poikilocytosis

Bone marrow smear:

- increased cellularity and greater proportion of RBC precursors demonstrating delicate open granular chromatin

Differential diagnosis of Macrocytic anemia

- causes

Nuclear maturation effects- B12 or folate deficiency

Myelodysplasia

Bone marrow failure states

Cytotoxic drugs

Ethanol

Stimulated erythropoeisis

Liver disease

Hypothyroidism

Pernicious anemia

- anemia type

- etiology

- clinical presentation

- lab findings

- treatment

Anemia type: megaloblastic anemia

Etiology:

- a B12 (cobalamin) deficiency as a result of asymptomatic chronic gastritis caused by an autoimmune disorder targeting parietal cells whose main job is to secrete acid and intrinsic factor used in the uptake of B12

- most common in N. European ancestory though all ethnicities can have it

- found in conjuctions with other autoimmune disorders (esp thyroid disorders), vitiligo, and diabetes mellitus

Clinical presentation:
- mild jaundice, pallor

- generalized weakness, anorexia, variable nonspecific abdominal complaints, weight loss, unexplained fever, symptoms of anemia

- Neurological symptoms:

   ~ paresthesias

   ~ loss of position and vibratory sense

   ~ ataxia

   ~ visual disturbances

   ~ spastic paresis

   ~ depression

   ~ psychosis

   ~ dementia

- may see in:

  ~ strict vegans, years after post gastrectomy, malabsorption syndromes (tropical sprue)

  ~ more typical in diseases affecting ileum

Lab findings:

- achlorhydria

- decreased gastric secretions

- extreme deficiency of IF in gastric juices

- low serum haptoglobin

- increased serum bilirubin

- elevated LDH

- low serum B12 (folate def will present this way too)

- elevation of methylmalonic acid and homocysteine in urine

- confirm diagnosis via detection of IF and parietal cell antibodies

Treatment:

- injectable vitamin B12 at diagnosis

- 1 mg maintenance doses monthly

- 1-2 mg oral daily dose may be adequate (not preferred)

- transfusions rarely required

- reticulocytosis 3-5 days after administration

Folic acid deficiency

- anemia type

- etiology

- clinical presentation

- lab findings

- treatment

Anemia type: megaloblastic anemia

Etiology:

- dietary deficiency associated with alcoholics, impaired absorption states (jejunum), excessive losses (hemodialysis patients), and conditions requiring increased folate (pregnancy, breast feeding, growth periods, hemolytic anemia)

Clinical presentation:

- alcoholics

- oral contraceptive use

- anticonvulsives (Dilantin, phenobarbital)

- cancer patients receiving methotrexate

Lab findings:

- Serum B12 = may be falsely depressed

- serum folate

- RBC folate = good indicator of tissue folate levels and may be slightly depressed in B12 deficiency

- Differentiating test = methylmalonic acid in urine/serum, presence = B12 def

Treatment:

- if suspected folate deficiency give 400 μg/day until

- confirmed folate deficiency gets 1 mg/day indefinate in chronic diseased patients and a couple of weeks for alcoholic patients

- underlying disorder needs to be treated

- folic acid supplementation should be given during pregnancy to reduce the incidence of neural tube defects