Chapter 8: Megaloblastic Anemia

What are causes of Megaloblastic anemia?

root cause:

• impaired DNA synthesis

• defective nuclear maturation

deficiencies of vitamin B12 / folate

What symptoms are associated with Megaloblastic Anemia?

• weakness

• fatigue

• shortness of breath

• lightheadedness

• yellow skin tint due to jaundice

Describe Vitamin B12.

• known as cobalamin

• essential nutrient

• decreased B12 is often accompanied by increased folate

What causes a B12 deficiency?

• dietary deficiency: vegan diet

• malabsorption:

  • pernicious anemia

  • gastrectomy

  • fish tapeworm

  • diseases of the ileum

  • chronic pancreatitis disease

• Other

  • hemodialysis

  • HIV/AIDS

  • alcohol

What is vitamin B12 needed for?

• RBC maturation in BM

• energy levels

• brain / nerve health → myelin synthesis

• DNA synthesis

  • breaks down homocysteine into methionine

• converts methylmalonyl CoA → Succinyl CoA

  • metabolism of amino acids / fatty acids

What role does vitamin B12 play in DNA synthesis?

• breaks down homocysteine → methionine

• transfer of methyl group from 5-methyltetrahydofolate → homocysteine

• generates methionine

What lab findings indicate a vitamin B12 deficiency?

• Ineffective:

  • erythropoiesis

  • granulopoiesis

  • thrombopoiesis

• Bone marrow:

  • changes in WBC precursors - bands and metamyelocytes

• Peripheral blood morphology

  • low levels: RBC,WBC, PLTs

  • macryocutes / macroovalocytes

  • Hj bodies, basophilic stipplings

  • Hypersegs

  • possible cabot rings and nRBCs

Describe Folate (folic acid).

• transfers carbon units in the form of methyl groups from donors to receptors

• deficiency = impaired cell replication

• circulates in blood as 5-methyl-tetrahydofolate

• increased demand during pregnancy

What can cause a folic acid deficiency?

• decreased dietary intake

• increased requirement

• malabsorption

• drug induced: methotrexate, pyrimethamine, phenytoin, alcohol, isoniazid, oral contraceptives

How are folate and vitamin B12 connected?

• filate carries methyl group

• vitamin B12 helps deliver the methyl group to homocysteine so it can become methionine

• without B12, folate is trapped as 5-methyl-THF and cannot be used

• causes ↑ homocysteine and impaired DNA synthesis

Describe the etiology of Pernicious Anemia.

• autoimmune disorder

• CD4 T cells attack parietal cells, interfere with IF secretion

• intestinal malabsorption of B12 due to lack of intrinsic factor

• production of antibodies to IF and gastric parietal cells

What are signs of Pernicious Anemia?

• fever

• loss of appetite

• weakness

• glossitis

• paraesthesia

• neurologic abnormalities

• paranoia

↓ serum/RBC folate

normal serum methylmalonic acid

↑ serum / plasma homocysteine

absent antibodies to IF or gastric parietal cells

• Folate deficiency

↓ serum vitamin B12

normal/ ↑ serum folate

normal/ ↑ RBC folate

↑ serum/plasma homocysteine

antibodies to IF/gastric parietal cells: seen in pernicious anemia

serum gastrin: marked elevated in pernicious anemia

stool analysis for parasites: Diphyllobothrium lactam may cause deficiency

• Vitamin B12 deficiency

MCV > 100

Serum B12: < 150 pg/ml

Serum folate > 4 ng/dl

• vitamin B12 deficiency

MCV > 100

Serum B12: 150-300 pg/ml

Serum folate 2-4 ng/dl

↑ MMA

normal: Homocysteine

• vitamin B12 deficiency

MCV > 100

Serum B12: 150-300 pg/ml

Serum folate 2-4 ng/dl

↑ MMA

↑ Homocysteine

• vitamin B12 deficiency possibly combined with Folate deficiency

MCV > 100

Serum B12: 150-300 pg/ml

Serum folate 2-4 ng/dl

normal MMA

normal: Homocysteine

• vitamin B12 deficiency

MCV > 100

Serum B12: 150-300 pg/ml

Serum folate 2-4 ng/dl

normal MMA

↑ Homocysteine

• folate deficiency

MCV > 100

Serum B12: >300 pg/ml

Serum folate < 2 ng/dl

• folate deficiency

What Lab results indicate Megaloblastic Anemia?

• decreased H/H

• macrocytosis/ pancyopenia

• MCV 100-150

• ↑ RDW

• Hypersegs

• teardrop cells, RBC fragments, Howell Jolly bodies, Cabot Rings

• low retic count

How is Megaloblastic Anemia treated?

• directed toward specific vitamin deficiency

• Cobalamin: IM for pernicious anemia

• folic acid given orally

What can measure the response to Megaloblastic Anemia treatment?

• after therapy, BM will reflect normoblastic cells

• peripheral blood retic count will normalize in 1 week

• H/H normalizes in 3 weeks