Macrocytic Anemias

Cell appearance

- MCV > 100fL
- MCHC is normal

Classified as

- megalobalstic
- non-megaloblastic

Megaloblastic

- Delayed nuclear maturation prevents cell division
- nuclear cytoplasmic asynchrony

Megaloblastic causes

- folate and B12 deficiency
- lack of intrinsic factor

- Myelodysplastic syndromes
- Acute Erythroid Leukemia (FAB-M6)
- Congenital Dyserythropoietic Anemia
- Reverse transcription inhibitors

Megaloblastic effects

- intramedullary hemolysis and disrupted DNA synthesis= anemia
- cell changes in other cells: skin, vaginal, uterine, cervical

Nonmegaloblastic

normoblastic maturation
- reticulocytes
- DNA is fine

Nonmegaloblastic causes

- newborns
- Reticulocytosis
- Chronic alcoholism
- Liver disease
- Bone marrow failure

B12 and Folate deficiency cause

thymidine nucleotide is impaired
- substitutes uridine
- causes apoptosis from breaks in strands

- cells that escape bone marrow, undergo ineffective hematopoiesis

Folate function

transfer carbon units (methyl groups) from donors to receptors
- in blood as 5-methyl-tetrahydrofolate (THF)

B12 and folate function

In the cell, a methyl group transfers from 5-methyl THF to homocysteine, converting it to methionine and generating THF
- requires vitamin B12

Folate deficiency

- Transported unbound
- Preventing the methylation of dUMP

Vitamin B12 decifiency

preventing the production of THF from 5-methyl THF

Folate source

- diet
- heat labile

Causes of folate deficiency

- malnutrition
- malabsorption
- drugs
- loss (dialysis)

Folate deficiency clinical

- megaloblastic anemia
- open tube neural defect

B12 daily requirements

- intake= 5 ug

- body stores= 2-5 mg

- 0.1% loss in urine and feces

Absorption of B12

- dietary= cobalamin (CBL)
- binds to R protein (haptocorrin) from salivary glands
- trypsin cleaves and bind to intrinsic factor
- released from IF, and transported as transcobalamin (TC)

Malabsorption of B12

- can't separate from food
- can't cleave from R-protein
- lack intrinsic factor

Bacteria

- H. pylori infection= parietal cells destroyed

- D. latum= can split CBL from IF

Pernicious Anemia

autoimmune impaired absorption of vitamin B12 from IF deficiency

Pernicious antibodies

- blocking= block b12 from IF= specific
- against parietal cell

screens for megaloblastic

- CBC
- Retic count
- WBC differential
- Serum bili
- LD

CBC for megaloblastic i

- pancytopenia
- decreased hgb and hct
- MCV= 100-150 fL
- reticulopenia

PB for megaloblastic

- oval macrocytes
- hypersegmented neutrophils
- aniso and poikilo-cytosis
- RBC inclusions

Reporting hypersegmentation

- 5 five-lobed neutrophils per 100 WBCs
- 1 six lobed
- should be >3

RBC life span is

short
- 27 - 75 days
- hemolysis

Chemistry tests in megaloblastic

- increase= bilirubin, urobilinogen, LDH are elevated
- Haptoglobin decreased
- Iron, ferritin, and EPO may be elevate

Bone marrow megaloblastic

- hypercellular
- ME ratio decreased (1:1, 1:3)
- nucleus doesn't mature with cytoplasm
- bands and giant metamyelocytes
- megakaryocytes= hypogranulation and hyperseg

diagnosis of megaloblastic

- Vitamin B12 levels
- Serum or RBC folate
- Methylmalonic acid (MMA) (increase in B12 def)
- Homocysteine levels (increase in both vitamin B12 and folate def)

megaloblastic treatment

treatment folate and B12 deficiencies

Macrocytic Non-megaloblastic Anemias

Macrocytosis without impairment of DNA synthesis
- liver disease
- alcoholism

alcohol effects

- Folate deficiency dietary decreased intake
- Reticulocytosis
- Bleeding, Hemolysis, Vacuolization of RBC

Liver disease lab

- macrocytes <115 fL
- target cells and acanthocytes (lipids)
- macrocytosis from lipids