Hemoglobinopathies

Question 1

Adult Hb

Answer 1

Alpha 2 beta 2

Question 2

Fetal Hb

Answer 2

Alpha 2 Gamma 2

Question 3

Thalassemia

Answer 3

Imbalance in globin synthesis: between alphas & betas

Question 4

Hemoglobinopathy

Answer 4

Abnormal protein is synthesized due to a mutation in the globin gene itself but the amount is normal

Hb S, C, D, O

Question 5

Alpha thalassemia

Answer 5

Decreased amount of alpha globin is made

You have 2 sets of 2 alpha globins

If 1/4 are deleted: silent carrier

Alpha thalassemia trait: deletion of 2/4; can be trans deleiton (one on each chromosome) or cis (two on one chromosome)
- Normal Hb/Hct, low MCV

Hemoglobin H Disease: 3/4 are deleted

• hemolytic anemia
• splenomegaly

Hydrops Fetalis: 4/4 are deleted

Question 6

Hydrops Fetalis

Answer 6

Edema in at least two fetal compartments

Poor prognosis for fetus

Question 7

Hemoglobin H Disease

Answer 7

Alpha thalassemia where 3/4 of the alpha globins are deleted

Leads to decreased alpha synthesis & oversynthesis of the betas to compensate; the disease is not due to missing alphas but due to excess beta

Hemolytic anemia

You get 2 forms of Hemoglobin instead:

HbH: beta 4 tetramers = very unstable, doesn’t carry O2 well, causes hemolysis

HbBarts: gamma 4 tetramers

Question 8

Beta Thalassemia

Answer 8

You have two genes–

Deletion of 1/2 = Beta Thalassemia Minor

• Carrier state
• Normal Hb/Hct, low MCV

Deletion of 2/2 = Beta Thalassemia Major

• Alpha tetramer forms = toxic, unstable, cause hemolysis
• Much more toxic than the beta 4 that’s made in alpha thalassemia
• RBC destroyed earlier on: in the bone marrow v. in alpha thalassemia, the RBC make it to the periphery
• Requires transfusion to survive + iron chelation, stem cell transplant
• Bone marrow expands in skull, long bone = abnormal site of RBC production

Question 9

Sickle Cell Anemia: genetics/pathology

Answer 9

Mutation in beta globin at 6th Amino Acid: Glutamic acid to Valine

They have Hb SS: two copies of these mutations

Causes polymerization of the red blood cells, especially during deoxygenation, which causes sickling/abnormal shape of RBCs

These sickle RBC get stuck in postcapillary venule –> vascular occlusion, which also involves RBC, platelets, wbc, vwf, etc.

Question 10

Sickle Cell Anemia: Clincal presentation

Answer 10

Pt’s get vaso-occlusive (pain) crises

Splenic sequestration: autosplenectomy secondary to infarction

Defect in splenic opsonization –> Howell Jolly bodies, susceptibility to encapsulated bacteria (S pneumonia, H influenza, N meningitidis, Salmonella), spenic sequestration

Acute chest syndrome: heart/lung complications that may be related to PE, pulm infarct, MI, pneumonias

Risk of stroke due to stenosis in circle of willis; must be on transfusion whole life

Question 11

How do you treat sickle cell anemia?

Answer 11

Penicillin prophylaxis

Hydroxyurea: works on red cell precursor to increase synthesis of fetal Hb & help decrease inflammation

Question 12

What is sickle trait?

Answer 12

Heterozygous for sickle cell anemia: Have Hb SA (where A is normal, adult Hb and S is sickled/mutated Hb chain)

Might be protective against malaria

All incoming division I athletes must be tested for sickle cell trait

Question 13

HbC

Answer 13

Crystals of HbC form in the middle of the RBC = “coffee bean cells”

Glutamic Acid –> Lysine at 6th amino acid (similar to sickle cell but it’s to Valine)

Question 14

HbSC

Answer 14

One HbC and one HbS (sickle cell)