Thalassemia

Question 1

thalassemia produces ____ anemia

Answer 1

microcytic– there is a defect in hemoglobin contents of rbc, making the cell smaller.

Question 2

a normal hb chain consists of:

Answer 2

4 heme molecules and 4 globin chains

Question 3

90% of hemoglobinmocules in adults exist as:

Answer 3

HbA form: 2 alpha 2 beta chains. there is a small amount of HbF: 2 alpha and 2 gamma chains, and small amount of HbA2: 2 alpha and 2 delta chains.

Question 5

quantitative hemoglobin disorders

Answer 5

quantitative: decreased/imbalanced production of globin chains:
- thalassemia alpha and beta: structurally “normal” but imbalanced
- HbE: mutation on globin chain; strucutrally abnormal. also microcytic.

Question 6

Qualitative inherited disorders of hemoglobin

Answer 6

Mutations in globin chain altering STUCTURE AND FUNCTION: Qualitative disorders are USUALLY NORMOCYTIC because the content is the same as a normal rbc but the function is off.

Decreased solubility:
HbS, HbC

Instability: precipitation sponateneoulsy or under oxidant stress;G6PD def.

Altered oxygen affinity: familial polycythemia (increasd affinity)

HbM= unable to carry oxygen –> cyanosis.

Question 7

differentiate between thalassemias

Answer 7

• Alpha thalassemia
• decreased synthesis of a globin chain
• Beta thalassemia
• decreased synthesis of b globin chain

Question 8

normally, there are ____ alpha globin gene locis. In alpha thalassemia, there is a ____ of one or more alpha gene loci.

Answer 8

normally, there are 4 alpha globin gene locis. In alpha thalassemia, there is a DELETION of one or more alpha gene loci.

Question 9

outline the alpha thalassemia genotypes/phenotypes

Answer 9

Question 10

cis vs trans inheritance

Answer 10

when 2 mising genes ae inherited from one parents = cis

when one missing gene is inherited from each parent = trans.

Question 11

CBC findings of an alpha thalassemia silent carreir and trait

Answer 11

silent carrier: usually normocytic and normochromic

trait: mild anemia, microcytosis, hypochromic, increased reticulocyte count, HgH ciruclating chains (4 beta globin chains making up a hemoglobin molecule and NO alpha)

Question 12

what is HgH. Also, in alpha thalassemia trait, what must you watch out for?

Answer 12

HgH- a hemoglobin molecule comprised of 4 hbB chains and no alpha chains.

• must watch out for iron overload or mislabeling for iron deficiency. the person may present with hypochromic, target cells, microcytic RBC with anemia. might look like Fe deficiency.

Question 13

CBC and clinical picture of someone with Hemoglobin H disease (A-/–)

Answer 13

CBC: moderate hemolytic anemia. Microcytosis. Hypochromia.

HbH circulating (no alpha chain in hemoglobin), you’d see hemogloin H bodies)

Clinical picture;

-hemolytic symptoms (splenomegaly), increased LDH, risk for iron overload, symptomatic anemia (fatigue)

Question 14

outline the inheritance pattern fo alpha thalassemia, and which types are more common in africa and SE Asia

Answer 14

Question 15

diagnosing alpha thalassemia. is ferritin elevated?

Answer 15

ferritin is NORMAL. beware of iron overload in patietns with alpha thalassemia

Question 16

treatment for alpha thalassemias (1,2, 3, and 4 deletions)

Answer 16

Question 17

normally, there are ___ beta globin allelles on chromosome 11. Mutations can be characterized as either:

Answer 17

b0 - no b globin production
• b+ - reduced b globin production

normally there’s 2 beta globin alleles

Question 18

in beta thalassemia, there’s excess ___ chains

Answer 18

alpha chains that precipitate out as FESSA BODIES

Question 19

outline the beta htalassemia genotype/phenotype

Answer 19

Question 20

CBC and HLPC findings of beta thalassemia minor

Answer 20

• mild anemia, microcytosis, hypochromia, and increased HgA2 seen on HLPC (increased level ofnon-affected globins)

Question 21

when would you make a diagnosis of beta thalassmia?

Answer 21

they are originally born healthy, because of fetal hemoglobin (A2G2), but as gamma and delta wear down, and beta is supposed to replace gamma, it becomes more and more apparent. often seen 6-12 months.

Question 22

how do thalassemias result in organ damage?

Answer 22

the alpha/beta chain imbalances cause hemolytic anemia and icnreased RBC turnover. there is risk of

1. iron overload
2. ineffective erythropoises resulting in marrow expansion and bone disease, extramedullary haemopoiesis and organomegaly, peripheral hemolysis and gall stones, and hypercoagulability and vascular disease
3. anemia.

all result in organ damage (heart, liver, endocrine)

Question 23

treatment for beta thalassemia minor, intermedia and major

Answer 23

Question 24

how to induce HbF. does this help with alpha or beta thalassemia?

Answer 24

can induce it with hydroxyurea. only helps with beta thalassemia (A2B-)because there is too much alpha and not enough beta. beta can be replaced with fetal hemoglobin to create globin chains A2G2. hydroxyurea induction of HbF would not help alpha thalassemia because alpha level is decreased and you can’t replace it with F. that might actually cause the presence of even more HbH bodies seen (rbc with no alpha Hb)

Question 25

beta thalassemia major requires life long transfusion and iron chelation and monitoring for organ dysfunction. because of transfusions, what must be watched out for?

Answer 25

must look out for iron loading with transfusion. 1ml of packed RBC contains 1 mg of iron. No mechanism to icnrease iron excretion. Iron remains in circulation and deposites in organs.

excess iron must be removed by chelation (either parenteral or oral)

Question 26

How to identify thalassemia carriers

Answer 26

microcytic?

if yes, is serum ferritin low or high?

if low, investigate cause of iron def. If MCV does not change after iron therapy and is still low, do Hb studies.

if serum ferritin is normal or high, do Hb studies off the bat.

Question 27

how to diagnose prenatally

Answer 27

• molecular diagnosis of fetus using fetal cells in maternal circulation, chorionic villus sample or amniocentesis.

Question 28

Outline the genotype and phenotype for HbE

Answer 28

HBA/E: normal heomglobin minimal microcytosis

HbE/E: mild asmptomatic anemia.

• HbE in general is not as bad as beta or alpha thalassemia, but it is still considered a QUANTITATIVE hemoglobinopathy since there is an actual decrease in proper globin synthesis.

Question 29

outline the genotype and phenotype for HbC. What can it be genetically coupled with to exacerbate symptoms?

Answer 29

Question 31

summary

Question 32

things you’d see on peripheral blood smear with alpha and beta thalassemia

Answer 32

alpha: hypochromia, microcytosis, possible anisopoikilocytosis
beta: hypochromia, microcytosis, target cells