Thalassemia

Question 1

Hemoglobin is made up of?

Answer 1

an iron containing hem ring surrounded by 4 globin chains, 2 alpha and 2 non-alpha

Question 2

Normal adult HB consists of?

Answer 2

2 alpha and 2 beta chains

Question 3

Normal fetal HB consists of?

Answer 3

2 alpha and 2 gamma chains

Question 4

HB A2 has?

Answer 4

2 alpha and 2 delta chains

Question 5

Fetal HB transition occurs?

Answer 5

transition from gamma to beta starts before birth, but at birth HB F is 80% and HB A is 20%. By 6 months, most infants have transitioned to mostly HBA

Question 6

Genetics of Alpha Thal?

Answer 6

-Autosomal recessive
-quantitative defect of alpha globin chain, leads to excess B globin chains
-Alpha chain synthesis controlled by 2 genes on each chromosome 16

Question 7

One gene deletion in Alpha thal?

Answer 7

silent carrier, asymptomatic, but needs preconception counselling
-may have MCV may be slightly lower

Question 8

Two gene deletion in Alpha Thal?

Answer 8

-Trait/minor
-mild microcytosis, erythrocytosis, hypochromia ,but not usually anemia

Question 9

Three gene deletion in Alpha Thal?

Answer 9

-HB H disease or intermedia
-results in significant HB H production, which consists of 4 beta chains
-results in microcytic anemia, hemolysis and splenomegaly
-not typically transfused unless growth failure

Question 10

4 gene deletion in Alpha Thal?

Answer 10

-HB Barts with 4 gamma chains
-usually results in non-immune hydrops fetalis, unless intrauterine transfusions

Question 11

Beta Thalassemia ?

Answer 11

Absent/deficient beta globin chains leading to excess alpha globin chains

Question 12

Genetics of Beta Thalassemia?

Answer 12

-Beta globin synthesis is controlled by one gene on each chromosome 11.
-Autosomal recessive
-occurs d/t one of the 200 point mutations on chromosome 11, and rarely as deletion
-Beta chain production can be normal or near absent, leading to varying degrees of excess alpha vs beta production

Question 13

Beta thalassemia Major or Cooley’s anemia?

Answer 13

Results from absent/reduced production of 2 beta globin genes, and excess alpha globin chains
-asymptomatic at birth until 6 months of life because sufficient HB F production
-splenomegaly, anemia, growth issues, boney changes, hemolysis, jaundice
-requires lifelong transfusions

Question 14

One gene defect in Beta Thal leads to?

Answer 14

Beta thalassemia trait, which is asymptomatic, but can have microcytosis and mild anemia

Question 15

Genetics of Beta Thalassemia intermedia?

Answer 15

-results from mildly reduced beta chains in both genes
-less severe than Major, but may require intermittent transfusions during periods of growth

Question 16

Alpha thal HB H-Constant Spring?

Answer 16

-elongated Alpha globin chain d/t termination codon mutation
-one parent has HB H constant spring and silent carrier; the other parent has alpha trait
-Phenotype is that these patients are more affected clinically than HB H

Question 17

Beta Thal can have a coexisting Hemoglobinopathy resulting in?

Answer 17

Decreased quality of Beta globin chain (HB S), AND decreased quantity from the thalassemia (HB S/beta thal zero or plus)

Question 18

Those with Thalassemia have microcytic anemia; what are the DD’s?

Answer 18

IDA, ACD, lead poisoning, Sideroblastic anemia

Question 19

What is the Mentzer index?
For Children, what is Mentzer index in Thal vs IDA?

Answer 19

-MVC/RBC
-less than 13=Thal
->13=IDA
-13=uncertain

Question 20

MCV in Thal VS IDA

Answer 20

-Thal= <75
-IDA= rarely <80 unless HCT is <30

Question 21

RDW in
Thal?
IDA?
Sideroblastic?

Answer 21

-thal=low in 50%
-IDA=elevated in 90%
-Sideroblastic=almost always elevated
-Therefore, normal RDW usually thalassemia, but elevated RDW cannot distinguish between IDA and sider

Question 22

BEST screening test for IDA in absence of inflammation?

Answer 22

Serum ferritin
-may need TIBC and iron and transferrin for inflammatory states as ferritin may be falsely elevated

Question 23

sideroblastic anemia excluded through which test(s)?

Answer 23

-peripheral smear and rarely Bone marrow aspirate

Question 24

How to rule out lead poisoning as cause of microcytic anemia?

Answer 24

• serum lead level

Question 25

How to rule out ACD as cause of microcytic anemia?

Answer 25

often normocytic, normochromic mild anemia

Question 26

What is Thal still suspected despite intensive BW work up?

Answer 26

HB electrophoresis

Question 27

What does HB electrophoresis look like for Beta Thal trait?

Answer 27

-reduced/absent HBA, elevated HBA2 and HBF
-BUT normal HBA2 does not rule out Beta thal trait with coexistent IDA, as IDA lowers HBA2 to normal level

Question 28

What does HB electrophoresis look like in adults with Alpha trait?

Answer 28

Normal

Question 29

If an infant has HB H or HB Barts on HB electrophoresis, they have?

Answer 29

Alpha Thalassemia

Question 30

What does the diagnosis of a patient with Beta Thal intermedia look like?

Answer 30

-with milder symptoms of microcytic anemia later in childhood/life

Question 31

Complications with Beta thal major or more severe intermedia?

Answer 31

Overstimulation BM from ineffective erythropoesis, iron overload from blood transfusions?

Question 32

Untreated infants with Beta Thal major will have?

Answer 32

-poor growth, boney deformities, jaundice

Question 33

Consequences of iron overload with chronic transfusions in Alpha and Beta Thal major?

Answer 33

-mainly iron deposits in visceral organs such as liver, heart and endocrine glands
-most death secondary to cardiac complications with Iron overload
-hypogonadism and DM may occur in teens and adults

Question 34

What finding most common on PE of symptomatic Thal pt?

Answer 34

-splenomegaly, which can lead to worsening anemia, and occasionally cause neutropenia, thrombocytopenia
-need for increased transfusions
-after splenectomy, thal pt can develop hypercoaguable state= arterial and venous thromboembolic events can be result

Question 35

When do blood transfusions start in patients with Beta Thal major?

Answer 35

-around 6 months of age with normal nadir of HB F
-keep HBA >95 and/or to promote normal growth

Question 36

Transfusions in HB H or Beta thal intermedia?

Answer 36

-only if clinically indicated for growth and development or if more severe phenotype ie., HB H constant spring or more severe Beta thal intermedia

Question 37

Why is splenectomy generally delayed until 4 y of age?

Answer 37

-because of spleen’s role in clearing bacteria and preventing sepsis.

Question 38

Which vaccinations required prior to splenectomy?

Answer 38

pneumococcal conjugate 13 valent series and pneumococcal polysaccharide 23 valent vaccine ONE Month prior to sx

Question 39

Serum ferritin as a marker for iron Cardiac overload?

Answer 39

• ferritin can be used as a marker of iron storage.
  -Ferritin <2500=improved survival
  -if liver dx present, ferritin unreliable

Question 40

Is folic acid supplementation indicated in pt with Thal?
What dose?

Answer 40

-if thal major/intermedia have a folate deficiency due to increased erythropoiesis
-1mg folic acid daily

Question 41

Is HU used to treat Thal?

Answer 41

Yes, in cases of non-transfusion dependent Beta Thal, such as intermedia or HB E/Beta Thal who have chronic anemia and require intermittent transfusion

Question 42

What are the positive effects of HU in some Beta Thal intermedia and HB E/Beta thal patients?

Answer 42

-positive effect on decreasing transfusion requirements EMH, ineffective erythropoiesis and decreasing spleen size

Question 43

What is the percentage of responders to partial responders to HU?

Answer 43

~50% responders
~79% partial responders
-therefore, significant # of patients are non-repsonders
-some have increase in HB F but transfusion requirements are unchanged