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Vitamin B-12 Def/Pernicious Anemia Kunwar Sohal, PGY-2

Vitamin B-12 Def/Pernicious Anemia

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Page 1: Vitamin B-12 Def/Pernicious Anemia

Vitamin B-12 Def/Pernicious Anemia

Kunwar Sohal, PGY-2

Page 2: Vitamin B-12 Def/Pernicious Anemia

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

Page 3: Vitamin B-12 Def/Pernicious Anemia

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

Page 4: Vitamin B-12 Def/Pernicious Anemia

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 hypersegmented neutrophils 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)

Page 5: Vitamin B-12 Def/Pernicious Anemia

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. hypersegmented neutrophil)

Page 6: Vitamin B-12 Def/Pernicious Anemia

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

Page 7: Vitamin B-12 Def/Pernicious Anemia

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

Pancreatitis Drugs (agents that block

absorption)

Page 8: Vitamin B-12 Def/Pernicious Anemia

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

Page 9: Vitamin B-12 Def/Pernicious Anemia

Schilling Test-Historic Interest

Saturate the transcobalamines and to "flush" any absorbed radiolabeled Cbl from its tissue and blood binding sites into the urine. Then 24 hr urine collection to determine % excretion from oral dose

Step 2 of test: Cbl and IF given to patient, and if absorption normalizes, PA is likely diagnosis

Page 10: Vitamin B-12 Def/Pernicious Anemia

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 neuro defs)

Few randomized trialsearly 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

Page 11: Vitamin B-12 Def/Pernicious Anemia

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

Page 12: Vitamin B-12 Def/Pernicious Anemia

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

Page 13: Vitamin B-12 Def/Pernicious Anemia

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

Page 14: Vitamin B-12 Def/Pernicious Anemia
Page 15: Vitamin B-12 Def/Pernicious Anemia

Sources

Pernicious Anemia. NEJM. Volume 337:1441-1448. November 13,1997. Number 20.

Diagnosis and treatment of vitamin B12 and folic acid deficiency. www.uptodate.com