pernicious anemia (vitamin b12 deficiency)

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 1999Rosenblatt 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

References• Pruthi RK, Tefferi A. Pernicious anemia revisited. Mayo Clin Proc 1994; 69:144.

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

• 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.

• Guéant JL, Safi A, Aimone-Gastin I, et al. Autoantibodies in

• pernicious anemia type I patients recognize sequence 251-256 in human

• intrinsic factor. Proc Assoc Am Physicians 1997; 109:462.