Vitamin B-12 Def/Pernicious Anemia

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  • 1. Vitamin B-12 Def/Pernicious Anemia
    KunwarSohal, PGY-2
  • 2. Where can I get me some?
    Animal products (meat and dairy products) provide the only dietary source of Cbl for humans
    Usual western diet contains 5 to 7 micrograms of cobalamin per day, while the minimum daily requirement is listed as 6 to 9 micrograms per day
    Total body stores of Cbl are 2 to 5 milligrams, approximately one-half of which is in the liver
    As a result, it takes years to develop vitamin B12 deficiency after absorption of dietary B12 ceases
  • 3. Absorption
    Dietary Cbl in the presence of acid and pepsin in the stomach is liberated from binding to protein and then quickly binds to R factors in saliva and gastric juice
    Cobalamin is freed from R proteins by pancreatic proteases and then binds specifically and rapidly to gastric-derived intrinsic factor (IF)
    Binds to specific ileal receptors from which it is absorbed in an energy requiring process that is still incompletely understood
  • 4. When to suspect Vit B12 def?
    Oval macrocytic red blood cells (ie, mean corpuscular volume >100 fL) on the peripheral blood smear, with or without anemia
    The presence of hypersegmentedneutrophils on the peripheral blood smear
    Pancytopenia (ie, the combination of anemia, thrombocytopenia, and neutropenia) of uncertain cause
    Unexplained neurologic signs and symptoms, especially dementia or weakness, sensory ataxia, and paresthesias
    Special populations, such as older adults, alcoholics, and patients with malnutrition are at high risk for the development
    Strict vegans (ie, Andrew Sampson, eat more eggs and dairy)
  • 5. Why pancytopenia?
    The megaloblast, the morphologic hallmark of the syndrome, is a product of impaired DNA formation which in turn is due to deficiencies of vitamin B12 (cobalamin, Cbl) or folic acid (a. macrocytic red blood cells, b. hypersegmentedneutrophil)
  • 6. Diagnosis
    Serum levels: blood samples should be obtained immediately on admission, before any meals have been taken and before any blood transfusions have been given, as even a single meal or transfusion may normalize serum concentrations of these vitamins
    >300 pg/mL normal; 200-300 borderline; <200 low
    What if borderline, or normal but suspicion high? Check serum concentrations of the metabolic intermediaries homocysteine (serum) and methylmalonic acid (serum and urine), appear to be more sensitive for the diagnosis of these deficiencies than serum vitamin levels, will be elevated
  • 7. Causes
    Gastric abnormalities: Pernicious anemia, Gastrectomy/Bariatric surgery, Gastritis, Autoimmune metaplastic atrophic gastritis
    Small bowel disease: Malabsorption syndrome, Ileal resection or bypass, Crohn's disease, Blind loops
    Diet: Strict vegans, Vegetarian diet in pregnancy
    Drugs (agents that block absorption)
  • 8. Pernicious Anemia
    Antibodies to Intrinsic Factor: highly confirmatory for the diagnosis of PA, with a sensitivity of 50 to 70 percent and a specificity approaching 100 percent
    Anti-parietal cell antibodies are much less sensitive and less specific
    An elevated serum gastrin or pepsinogen levels is highly sensitive for the diagnosis of PA (90 to 92 percent), although these tests lack specificity
  • 9. Schilling Test-Historic Interest
    Step 2 of test: Cbl and IF given to patient, and if absorption normalizes, PA is likely diagnosis
    Saturate the transcobalamines and to "flush" any absorbed radiolabeledCbl from its tissue and blood binding sites into the urine. Then 24 hr urine collection to determine % excretion from oral dose
  • 10. Treatment
    Pernicious anemia (PA) is typically treated with IM Cbl
    1 mg every day for one week, followed by 1 mg every week for four weeks and then, if the underlying disorder persists, as in PA, 1 mg every month for the remainder of the patient's life
    Some use smaller diagnosis, however medication is nontoxic (lower doses also give slower responses, which can be concerning for those with severe neurodefs)
    Few randomized trialsearly word is that oral in newly diagnosed patients was found to be as effective as intramuscular administration in obtaining short-term haematological and neurological responses in vitamin B12-deficient patients (need higher dose and pt compliance
  • 11. Preventive Measures
    Vegetarians: convince them to start eating meat OR supplement their diet (esp in pregnancy, breast feeding, infacnt deficient)
    Gastric Surgery: supplementation with large doses of oral Cbl, preferably on an empty stomach, is warranted
    Nitrous Oxide Exposure: inactivates cobalamin and its use in anesthesia may precipitate rapid neuropsychiatric deterioration in Cbl-deficient subjects
  • 12. Treatment response
    Elevated levels of serum iron, indirect bilirubin, and LDH fall rapidly within the first one to two days following treatment with parenteral vitamin B12; bone marrow erythropoiesis also changes from megaloblastic to normoblastic during this period
    Pt will symptomatically feel much better during this time also
    Hypokalemia during the early response is due to the marked increase in potassium utilization during production of new hematopoietic cells
    If the patient is anemic, there will be a reticulocytosis in three to four days, peaking at one week, followed by a rise in hemoglobin and a fall in red blood cell mean corpuscular volume (nml Hg in 8 weeks)
    Neurologic abnormalities, if present, improve over the ensuing three months, with maximum improvement attained at six to twelve months
  • 13. Malignancy?
    Patients with PA appear to have an increased risk of developing gastric or colorectal adenocarcinoma, but the data are not entirely conclusive
    Recommended to periodically monitor stools in these patients for the presence of blood
  • 14.
  • 15. Sources
    Pernicious Anemia. NEJM. Volume 337:1441-1448. November 13,1997. Number 20.
    Diagnosis and treatment of vitamin B12 and folic acid deficiency.