Anemia, Megaloblastic

Anemia, Megaloblastic ¹⁷

ICD-10CM #	D51.0	Vitamin B₁₂ deficiency anemia due to intrinsic factor deficiency
	D51.1	Vitamin B₁₂ deficiency anemia due to selective vitamin B₁₂ malabsorption with proteinuria
	D51.3	Other dietary vitamin B₁₂ deficiency anemia
	D51.8	Other vitamin B₁₂ deficiency anemias
	D52.0	Dietary folate deficiency anemia
	D52.1	Drug-induced folate deficiency anemia
	D52.8	Other folate deficiency anemias
	D52.9	Folate deficiency anemia, unspecified
	D53.1	Other megaloblastic anemias, not elsewhere classified
	D53.0	Protein deficiency anemia
	D53.2	Scorbutic anemia
	D53.8	Other specified nutritional anemias
	D53.9	Nutritional anemia, unspecified

Cobalamin (Cbl) Deficiency

Nutritional CBL Deficiency (Insufficient CBL Intake)

Vegetarians, vegans, breastfed infants of mothers with pernicious anemia.

Abnormal Intragastric Events (Inadequate Proteolysis of Food CBL)

Atrophic gastritis, partial gastrectomy with hypochlorhydria.

Loss/Atrophy of Gastric Oxyntic Mucosa (Deficient Intrinsic Factor [IF] Molecules)

Total or partial gastrectomy, pernicious anemia (PA), caustic destruction (lye).

Abnormal Events in Small Bowel Lumen

Inadequate pancreatic protease (R-CBL not degraded, CBL not transferred to IF).
- Insufficiency of pancreatic protease-pancreatic insufficiency.
- Inactivation of pancreatic protease-Zollinger-Ellison syndrome.
Usurping of luminal CBL (inadequate CBL binding to IF).
- By bacteria-stasis syndromes (blind loops, pouches of diverticulosis, strictures, fistulas, anastomoses); impaired bowel motility (scleroderma, pseudoobstruction), hypogammaglobulinemia.
- By Diphyllobothrium latum.

Disorders of Ileal Mucosa/IF Receptors (IF-CBL not Bound to IF Receptors)

Diminished or absent IF receptors-ileal bypass/resection/fistula.
Abnormal mucosal architecture/function-tropical/nontropical sprue, Crohn disease, TB ileitis, infiltration by lymphomas, amyloidosis.
IF-/post IF-receptor defects-Imerslund-Gräsbeck syndrome, TC II deficiency.
Drug-induced effects (slow K, biguanides, cholestyramine, colchicine, neomycin, PAS).

Disorders of Plasma Cbl Transport (Tc II-Cbl Not Delivered to Tc II Receptors)

Congenital TC II deficiency, defective binding of TC II-CBL to TC II receptors (rare).

Metabolic Disorders (Cbl Not Utilized by Cell)

Folate Deficiency

Nutritional Causes

Decreased dietary intake-poverty and famine (associated with kwashiorkor, marasmus), institutionalized individuals (psychiatric/nursing homes), chronic debilitating disease/goats’ milk (low in folate), special diets (slimming), cultural/ethnic cooking techniques (food folate destroyed) or habits (folate-rich foods not consumed).
Decreased diet and increased requirements:
- Physiologic: pregnancy and lactation, prematurity, infancy.
- Pathologic: intrinsic hematologic disease (autoimmune hemolytic disease), drugs, malaria; hemoglobinopathies (SS, thalassemia), RBC membrane defects (hereditary spherocytosis, paroxysmal nocturnal hemoglobinopathy); abnormal hematopoiesis (leukemia/lymphoma, myelodysplastic syndrome, agnogenic myeloid metaplasia with myelofibrosis); infiltration with malignant disease; dermatologic (psoriasis).

Folate Malabsorption

With normal intestinal mucosa:
- Some drugs (controversial).
- Congenital folate malabsorption (rare).
- With mucosal abnormalities-tropical and nontropical sprue, regional enteritis.

Defective Cellular Folate Uptake-Familial Aplastic Anemia (Rare), Inadequate Cellular Utilization

Drugs (Multiple Effects on Folate Metabolism)

Alcohol, sulfasalazine, triamterene, pyrimethamine, trimethoprim-sulfamethoxazole, diphenylhydantoin, barbiturates.

Miscellaneous Megaloblastic Anemias (Not Caused by Cbl or Folate Deficiency)

Congenital Disorders of DNA Synthesis (Rare)

Orotic aciduria, Lesch-Nyhan syndrome, congenital dyserythropoietic anemia.

Acquired Disorders of DNA Synthesis

Thiamine-responsive megaloblastosis (rare).

Malignancy-erythroleukemia-refractory sideroblastic anemias-all antineoplastic drugs that inhibit DNA synthesis.
Toxins: alcohol.