ANEMIA, PERNICIOUS

ANEMIA, PERNICIOUS - Abdulrazak Abyad, MD, PhD, MBA, MPH, AGSF
BASICS
DESCRIPTION
Pernicious anemia is a disorder due to vitamin B12 deficiency. It is invariably associated with atrophic gastritis and histamine-fast achlorhydria. Vitamin B12 cannot be absorbed in the terminal ileum without intrinsic factor (a secretion of the parietal cells of the gastric mucosa). Its usual course is slowly progressive.
• System(s) Affected: Gastrointestinal; Hematologic/Lymphatic/Immunologic; Nervous
• Synonym(s): Addison anemia; Megaloblastic anemia due to B12 deficiency
ALERT
Geriatric Considerations
More common in this age group and often in association with other autoimmune disorders, depression, and dementia
Pediatric Considerations
• Juvenile pernicious anemia occurs in older children and is the same in most respects as in adults.
• Congenital pernicious anemia is usually evident before 3 years of age.
Pregnancy Considerations
Untreated pernicious anemia in pregnancy may cause neural tube defects.
GENERAL PREVENTION
• Early detection of anemia
• Workup of anemia
EPIDEMIOLOGY
Predominant sex: Male = Female
Incidence
Unknown
Prevalence
Older adults (>60 years)
RISK FACTORS
• Vegetarian diet, without B12 supplementation
• Gastrectomy
• Blind loop syndrome
• Fish-tapeworm infestation
• Malabsorption syndromes
• Drugs: Oral calcium-chelating drugs, amino salicylic acid, and biguanides
• Chronic pancreatitis
• Alcoholism
Genetics
• HLA-DR2, HLA-DR4: Present in the rare form of pernicious anemia that is hereditary
• Endemic area: Northern Europe, including Scandinavia
ETIOLOGY
• Atrophic gastric mucosa
• Intrinsic factor deficiency
• Probable autoimmunity against gastric parietal cells
• Autoimmunity against intrinsic factor
ASSOCIATED CONDITIONS
• Autoimmune diseases including rheumatoid arthritis, IgA deficiency
• Graves disease
• Myxedema
• Iron deficiency
• Thyroiditis
• Vitiligo
• Idiopathic adrenocortical insufficiency
• Hypoparathyroidism
• Agammaglobulinemia
• Tropical sprue
• Celiac disease
• Crohn's disease
• Infiltrate disorders of the ileum and small intestine


DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Anorexia, weight loss
• Depression
• Position sense: Decreased
• Prematurely gray-haired
• Tinnitus
Physical Exam
• Abnormal reflexes
• Ataxia
• Atrophic glossitis
• Babinski's sign: Positive
• Confusion
• Congestive heart failure
• Dementia
• Exertional dyspnea
• Extremity numbness
• Extremity paresthesias
• Hepatomegaly
• Hypoalqesia in "sock and glove" distribution
• Pallor
• Palpitations
• Poor finger coordination
• Purpura
• Romberg's sign: Positive
• Skin pigmentation increased
• Sore tongue
• Splenomegaly
• Tachycardia
• Vertigo
• Vibration sense: Decreased
• Vitiligo
• Weakness
TESTS
• Schilling test plus intrinsic factor: Normal vitamin B12 absorption
• Schilling test: Decreased vitamin B12 absorption
• Gastric analysis: Achlorhydria
Lab
• Achlorhydria
• Anisocytosis
• Haptoglobin decreased
• Howell-Jolly bodies
• Hypergastrinemia
• Hypersegmented neutrophils
• LDH increased
• Leukopenia
• Macrocytic anemia; MCV: 110-140
• Pentagastrin stimulation: Stomach pH >6
• Serum ferritin increased
• Serum vitamin B12 level 100 pg/mL (74 pmol/L)
• Peripheral blood smear: Macro-ovalocytes
• Poikilocytes
• Thrombocytopenia
• Anti-intrinsic poikilocytosis factor antibody
• Anti-parietal cell antibody
• Direct hyperbilirubinemia
• Disorders that may alter lab results
- Falsely elevated MCV
 Cold agglutinins
 Hyperglycemia
 Marked hyperleukocytosis
- Falsely normal serum vitamin B12 level
 Myeloproliferative disorders
 Liver disease
- Falsely low serum B12 level
 Multiple myeloma
 Oral contraceptive intake
 Pregnancy
 Folate deficiency
 Transcobalamin I deficiency
 Recent isotope administration
Diagnostic Procedures/Surgery
• Bone marrow aspiration
• Detailed history and physical exam
Pathological Findings
• Bone marrow: Hypercellular, macrocytes, iron stores increased
• Nests of megaloblasts
• Giant metamyelocytes
• Macro-polymorpho-leukocytes
• Hypersegmented neutrophils
• Stomach: Atrophic gastritis, goblet cells increased
• Parietal cell atrophy
• Chief cell atrophy
• Gastric cytology: Cellular atypia
• Spinal cord: Myelin degeneration of the dorsal and lateral tracts
• Peripheral nerve degeneration
• Degenerative changes of the posterior root ganglia
DIFFERENTIAL DIAGNOSIS
• Folic acid deficiency
• Myelodysplasia
• Neurological disorders without B12 deficiency
• Liver dysfunction
• Hypothyroidism
• Hemolysis or bleeding
• Drug effects
• Alcoholism
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient
• Treatment must be continued for life
• Identification and treatment of the underlying disorder
ALERT
Folic acid treatment without vitamin B12 in patients with pernicious anemia is contraindicated.
Diet
Emphasize meat, animal protein foods, and legumes unless contraindicated.
Activity
Unlimited
MEDICATION (DRUGS)
• Parenteral Vitamin B12 (cyanocobalamin)
- 1,000 mcg SQ for each dose
- Administer daily for the 1st week
- Administer weekly for 1 month
- Monthly injections for remainder of life (patients may be taught to give self-injection)
• Precautions: Do not give folic acid supplements without vitamin B12, may cause fulminant neurological deficit.
FOLLOW-UP
PROGNOSIS
• Anemia reversible with parenteral vitamin B12
• Neurologic effects not reversible with parenteral vitamin B12
COMPLICATIONS
• Hypokalemia may complicate the 1st week of treatment.
• Central nervous system symptoms may be permanent if patient is not treated in 6 months after the symptoms begin.
• Gastric polyps
• Stomach cancer
- There is a 3-fold likelihood of developing gastric carcinoma.
- Suggest endoscopy approximately every 5 years even if asymptomatic.
PATIENT MONITORING
• Monthly injections of vitamin B12
• Endoscopy every 5 years to rule out gastric carcinoma
REFERENCES
1. Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: WB Saunders; 1996.
2. Chui CH, Lau FY, Wong R, et al. Vitamin B12 deficiency-need for a new guideline. Nutrition. 2001;17:917-920.
3. Wheby MS, ed. The Medical Clinic of North America: Anemia. Vol. 76. Philadelphia, PA: WB Saunders; 1992.
4. Williams WJ, Beutler E, Erslev AJ, et al., eds. Hematology. 4th ed. New York, NY: McGraw-Hill; 1990.
MISCELLANEOUS
See also: Tropical Sprue