Hemoglobinopathies 9/27

Question 1

What is the genetic mechanism for abnormal globin chain production?

Answer 1

Single amino acid substitution

Question 2

What is the main characteristic of thalassemias?

Answer 2

Reduced or absent production of one or more globin chains.

Question 3

What happens to the excess, unpaired globin tetramers?

Answer 3

Precipitate to form Heinz bodies, which result in accelerated RBC destruction

Question 4

What is the main mechanism in alpha thalassemia?

Answer 4

Whole gene deletion.

Question 5

Silent carrier a-thalassemia

Answer 5

-a/aa

Normal/slightly low MCV

Could have HbH inclusions

Question 6

a-thalassemia minor

Answer 6

-a/-a or –/aa

No clinical disease. No or mild anemia. Low MCV. TARGET CELLS. HbH inclusions

Question 7

HbH disease

Answer 7

–/-a

Formation of unstable B4 (HbH) which precipitated in RBCs.
RBCs removed by spleen (chronic hemolysis).

Life-long mild to moderate anemia (Hb 8-12). Low MCV. Lots of HbH inclusions.

Normal life expectancy.

Question 8

HbH Constant Spring disease

Answer 8

–/Aa

Mutation of termination codon -> elongated alpha chain.

Diagnosed on electrophoresis (1.5-2.5% HbCS)

Question 9

Bart’s Hydrops Fetalis

Answer 9

–/–

Exclusively SE Asians

Only HbB (HbBarts) present: y4

Very high oxygen affinity. LETHAL. stillbirth or death within hours of birth.

Question 10

What is the characteristic of beta thalassemia?

Answer 10

Impaired production of B globin chains.

Excess a-globin chains unstable - precipitate.

Question 11

Genetics of B-thalassemia minor?

Answer 11

Heterozygotic with one normal B-globin allele & one B-globin thalassemic allele

CBC: HYPOCHROMIA & MICROCYTOSIS

TARGET CELLS PRESENT

Question 12

B-Thalassemia major clinical manifestations

Answer 12

Symptoms emerge 6 months after birth.

Severe & chronic anemia
Stigmata of chronic hemolysis
Organ damage from iron overload
Expanding mass of BM erythroid progenitors

Chipmunk faces
Liver & gallbladder
Splenomegaly

Endocrine abnormalities- hypogonadism, growth failure, diabetes, hypothyroidism

Cardiopulmonary- heart failure & arrhythmias, cardiomyopathy, pulmonary hypertension

Parvovirus B19

Question 13

B-thalassemia major laboratory findings:

Answer 13

HYPOCHROMIC & MICROCYTIC

⬆️WBC, normal platelet count

⬆️serum iron, transferrin saturation, ferritin

Erythroid hyperplasia in BM

Only HbF and HbA2 are present

Question 14

B-thalassemia major treatment: (6)

Answer 14

1. Chronic hyper transfusion therapy: maintain steady state Hgb 9-10 g/dL
2. Iron overload chelation therapy
3. Splenectomy
4. Osteoporosis prevention
5. Folate supplementation
6. Hematopoetic stem cell transplant

Question 15

Describe Unstable Hemoglobins

Answer 15

Autosomal dominant heterozygotes only.

Denaturion -> Heinz bodies -> removed in spleen -> hemolysis

Question 16

How do you diagnose unstable Hemoglobins?

Answer 16

• Blood smear: irregular contracted cells, bite cells
• Heinz bodies
• isopropanol precipitation test

SPLENECTOMY

Question 17

What is the genetic mechanism for HbC?

Answer 17

2 normal alpha chains, 2 variant beta chains.

Swap LYSINE for GLUTAMATE

When HgC is in deoxygenated state, it precipitates as crystal

Question 18

HbC presentation and diagnosis

Answer 18

Mild. TARGET CELLS. Bone pain. Retinopathy angioid streaks.

Question 19

What are 5 complications of SCA?

Answer 19

1. Sepsis
2. Priapism
3. M.I.
4. Multi organ failure
5. Transfusion reaction

Question 20

Sickle cell disease treatments besides transfusion? (4)

Answer 20

1. Hydroxyurea: ⬆️HgF (fetal hemoglobin)
2. Decitabine: beneficial for pt’s intolerant to Hydroxyurea
3. Penicillin
4. Follic acid