Pernicious Anemia

Elliot Stieglitz

CBC and Iron

Electropheresis

Hemolytic Studies

Autoimmune

Pernicious Anemia

Post Rx CBC

Objectives

Definition
Pathophysiology Epi Clinical Symptoms PE findings Lab Treatment

Definition

Pernicious

highly destructive

injurious
baneful

deadly

Vitamin B12

Only metabolized by bacteria (fermentation) Meat and milk Most animals capable of conversion

DNA Synthesis

MMA and HC
Thymdine synthesis

B12 Deficiency

Inadequate diet Loss of gastric mucosa Functionally abnormal IF Insufficient pancreatic enzymes (ZE) Ileal dysfunction Medication (Metformin and PPIs)

B12 and Folate

H. Pylori

Turkish study Of 138 B12 deficient patients, 77 had HP

In all 31 who had HP eradicated B12 returned to normal w/o B12

FUT2 secretor gene

Pathophysiology

Failure of gastric parietal cells to produce Intrinsic Factor (IF)

Text

Antibodies

IgG Type 1 vs II

Placenta

Autoimmune

HLA A2, A3, A7 and Blood group A Antiparietal cell Abs in 90% of PA

H-K ATPase Chief Cells

5% of population with Abs 50% with Abs have PA Associated with other autoimmune disease:

Thyroid, DM1, Addisons, UC

History

First described by Dr Thomas Addison Fatal within 3 years till 1920

Epidemiology

Incidence: 10 per 100,000 Gender: Equal in US Age: 40-70

Race Congenital

Juvenile PA

Older children + anti IF Abs - anti parietal Abs 50% with other autoimmune disease mucocutaneous candidiasis 45 cases documented in literature by 1999
Rosenblatt DS, Whitehead VM. Cobalamin and folate deficiency: acquired and hereditary disorders in children. Semin Hematol. 1999 Jan;36(1):19-34.

Clinical Features

Weight loss Anemia: well tolerated Tongue Neurological

parasthesias, numbness, tingling, ataxia various hypotheses

DNA Synthesis

MMA and HC
Thymdine synthesis

Pica

Unclear etiology but associated w/ IDA Chicken or the Egg? Odd cravings for non nutritional items Pagophagia- Rx Glossitis? Border of Turkey and Iran 1960s

PE Findings

Waxy pallor Icterus Flabby Beefy red tongue

Glossitis

Lab Evaluation

MCV, MCH, MCHC

Confounding factors

Leukopenia and thrombocytopenia MMA and HC Intramedullary hemolysis

Schilling Test

Treatment

Vitamin B12

Cyanocobalamin or hydroxocobalamin

IM, SQ vs PO Nasal

Whipple Procedure

Summary

Vit B 12 Deficiency Iron Deficiency Hemolytic Anemia Pica IF Ab

Allen RH, Stabler SP, Savage DG, Lindenbaum J. Metabolic abnormalitiesin cobalamin (vitamin B12) and folate deficiency. FASEB J 1993;7:1344.

References

Green R, Kinsella LJ. Current concepts in the diagnosis of cobalamindeficiency. Neurology 1995; 45:1435. Tefferi A, Pruthi RK. The biochemical basis of cobalamin deficiency.Mayo Clin Proc 1994; 69:181. Anthony, CA. Megaloblastic anemias. In: Hematology: Basic Principlesand Practice, 2nd ed, Hoffman, R, Benz, EJ, Shattil, SJ, et al (Eds), Churchill Livingston, New York 1995. p.552. Carmel R. Prevalence of undiagnosed pernicious anemia in the elderly.Arch Intern Med 1996; 156:1097. Toh BH, van Driel IR, Gleeson PA. Pernicious anemia. N Engl J Med1997; 337:1441. Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood 2008; 112:2214. Guant JL, Safi A, Aimone-Gastin I, et al. Autoantibodies in