Hematology: Thalassemia

97% of normal adult hgb is

hgb A

Normal beta genes are located on what chromosome

chromosome 11, one from each parent

Normal alpha genes are located on what chromosome

chromosome 16, two from each parent

When does B thalassemia manifest?

after the gamma chain switches to beta

Imbalance of B globulin causes what anemia

microcytic hypochromic anemia

In B thalassemia, what happens to the excess alpha chains

become inclusions in RBC and the RBCs are destroyed by BM macrophages

What mechanisms does B thalassemia use

iron accumulation in RBCs and inflammatory cytokines

B0

mutation causes no B chain production

B+

mutation resulting in decreased B chain production (5%-30%)

Bsilent

mutation resulting in mildly decreased B chain production

SB0

no B or S chain, increased gamma chain

SBlepore

SB gene fusion, small amounts of SB chain and increased gamma

homozygous B thalassemia

B thalassemia major

heterozygous B thalassemia

B thalassemia minor (usually asymptomatic)

B thalassemia major stimulates the production of what

EPO

Symptom of B thalassemia major due to erythroid hyperplasia

frontal bossing of skull (hair-on-end)

RBC morphology seen in B thalassemia major

target cells, schistocytes, basophilic stippling, nRBC

Retics in B thalassemia major

reticulocytosis (2-8%)

What hgb takes over in B thalassemia major

hgb F

Homozygous HPFH

only Hb F is synthesized (100%)

Heterozygous HPFH

Hb F (10-30%)

What stain is used to measure HPFH

Kleihauer-Betke (fetal cell stain)

When does A thalassemia manifest

immediately at birth

A thalassemia silent carrier

missing one of 4 functional genes, protective against malaria

A thalassemia trait

missing 2 functioning genes 2, normal electrophoresis

Hemoglobin H

excessive B chains form tetrads

Hgb H affect on RBC

shortens life span (chronic hemolytic anemia)

Oxygen levels in Hgb H

tissue hypoxia

Hgb H electrophoresis

5-40%

Hgb H RBC morphology

cresyl blue golf ball apperance

How do thalassemia iron studies differ from other anemias

all normal or iron/ferratin slightly elevated

How do you differentiate between A and B thalassemia

cellulose acetate electrophoresis