Hemoglobinopathies

Question 1

What globin chains are hemoglobin A composed of?

Answer 1

2 beta and 2 alpha chains

Question 2

What is Hgb A2 composed of?

Answer 2

Two alpha chains and 2 delta chains

Question 3

What is Hgb F composed of?

Answer 3

Two alpha and 2 gamma chains.

Question 4

What are the clinical and laboratory features of Beta thalassemia trait?

Answer 4

+/- mild anemia with no symptoms, elevated Hgb A2>3.5, microcytosis, hypochromia, target cells.

Question 5

What do you find on electrophoresis for beta thalassemia trait?

Answer 5

Hgb A2>3.5% (3.5-8) and Hgb F 1-2%.

Question 6

What do you find on electrophoresis for beta thalassemia intermedia (Hgb F value)?

Answer 6

Hgb F will be much higher (30-75%). Hgb A2 will be higher than what you see in Minor Dx

Question 7

What do you find on electrophoresis in beta thalassemia major (Hgb F)?

Answer 7

Hbg F>95%. There is 0 Hbg A.

Question 8

What infection can happen as a result of chelator therapy?

Answer 8

Yersinia infection

Question 9

What are some general side effects of chelator therapy?

Answer 9

Growth retardation, skin reaction, cytopenias, GI side effects, hepatic/renal abnormalities, hearing/vision issues.

Question 10

What is the mechanism of action with Luspatacerpt?

Answer 10

It binds TGF beta superligand that binds to activin causing a ligand trap and increased late stage erythropoiesis.

Question 11

What complication should you be mindful of if using Luspatacerpt in those with splenectomy?

Answer 11

Increased thrombosis

Question 12

What is hemoglobin barts?

Answer 12

4 gamma chains in alpha thalassemia

Question 13

What is hemoglobin H?

Answer 13

4 beta chains in alpha thalassemia

Question 14

What are the clinical and laboratory differences between alpha silent carrier and alpha trait?

Answer 14

Alpha silent carrier-normal to very mild anemia, no morphological abnormalities, very mildly low MCV
Alpha Trait-mild anemia/microcytosis with no symptoms, target cells/hypochromia

Question 15

For both alpha silent carrier and alpha trait what are the results of the Hgb electrophoresis?

Answer 15

In both conditions the Hgb A2 concentration will be normal.

Question 16

Summarize the key clinical features of Hemoglobin H disease

Answer 16

Splenomegaly, moderate anemia, high reticulocyte, hypochromia, very variable Red cell size/shape

Question 17

Will Hemoglobin H patients typically require transfusions?

Answer 17

No they generally do not require transfusions. Unless they need a surgery or for instance develop a severe infection (situational).

Question 18

What is the MCV in constant spring?

Answer 18

The MCV will be normal!

Question 19

In hemoglobin M disease what is the principal pathology present?

Answer 19

The iron in hemoglobin is oxidized Fe+3 (ferric state) from Fe+2 and thus is unable to bind oxygen. This causes a functional anemia.

Question 20

When hemoglobin variants have a high O2 affinity what happens to the O2 dissociation curve?

Answer 20

It shifts to the left.

Question 21

For alpha thalassemia trait which population carries the cis configuration vs the trans configuration?

Answer 21

African American/mediterranean-trans configuration (-,a)(-,a)
Asian, cis-(-,-) (a,a)

Question 22

What is the genotype for Hemoglobin Constant Spring?

Answer 22

(–/aCS,a)

Question 23

What type clinical severity of symptoms do you expect from Hemoglobin Constant Spring?

Answer 23

These patients have much more significant anemia/splenomegaly and symptoms compared to hemoglobin H disease. These patients more often will require intermittent transfusion support compared to Hgb H disease.

Question 24

How does Hemoglobin E carriers present clinically and homozygotes present? What is the MCV? What causes them to have symptoms?

Answer 24

Carriers are silent and have no symptoms at all w/low MCV. Homozygotes are also asymptomatic (unless they have co-inheritance of Beta or alpha thal).

Question 24

What population do we mostly see Hemoglobin E disease?

Answer 24

SE Asian

Question 25

The hemoglobin C variant is predominantly seen in which ethnicity?

Answer 25

Africans/African Americans

Question 26

In Hemoglobin C disease which patients actually develop symptoms?

Answer 26

Homozygotes and those with HbC/beta thal (mild -mod anemia with splenomegaly, worse with stress e.g. infection).