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Heme > Thalassemia > Flashcards

Thalassemia Flashcards

1
Q

What 2 types of abnormal Hgb can patients with alpha-thal have and what chains are each one made of?

A
  1. Hgb H: 4 beta chains

2. Hgb Bart’s: 4 gamma chains

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2
Q

What types of Hgb are increased in beta-thal?

A

Increased Hgb F or Hgb A2.

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3
Q

What are the 3 classifications of thalassemia?

A
  1. Major
  2. Intermediate
  3. Minor
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4
Q

Thalassemia majors involve what genes?

A

Beta genes on chromosome 11. The other 2 categories involve both beta and alpha genes.

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5
Q

Beta-thal is most common in patients with what kind of heritage?

A

Mediterranean.

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6
Q

Why is anemia seen in Beta-thal?

A

Unpaired alpha chains form hemichromes (and inclusion bodies?) that induce apoptosis in erythroblasts. Basically the hemichromes alter the functionality of the RBC, it sucks, so it is murdered.

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7
Q

What molecule is on the outside of normal RBCs?

A

Choline containing phospholipids.

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8
Q

What molecule is on the inside of normal RBC membranes?

A

Phosphatidylserine

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9
Q

What enzyme normally maintains RBC membranes?

A

Flipase

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10
Q

What 4 factors related to thalassemia RBCs lead to a hypercoagulable state?

A
  1. Membrane damage by alpha hemichromes and oxidant stress
  2. Phosphatidylserine exposed out of membrane
  3. Increase in free plasma hemoglobin
  4. Increase in platelet activation
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11
Q

What therapy reduces thrombotic complications in thalassemia?

A

Transfusions

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12
Q

What 2 things does the exposure of phosphatidylserine on the outside of RBCs induce?

A
  1. Apoptosis: serves as the recognition site

2. Increases thrombin production

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13
Q

What’s the advantage of being a carrier of a Hgb mutation?

A

Decreases susceptibility to malaria.

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14
Q

Hydrops fetalis is characterized by an inability to produce which globin chain? Outcome?

A

Alpha chain. Not a viable pregnancy: death occurs in utero.

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15
Q

What are the 3 forms of adult hemoglobin and what chains comprise each of them?

A
  1. Hgb F: 2 alpha + 2 gamma
  2. Hgb A2: 2 alpha + 2 delta
  3. Hgb A: 2 alpha + 2 beta
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16
Q

What is responsible for the thinning and deformity of bones seen in beta-thal?

A

Result of bone marrow expanding within the bones i.e. osteopenia, jacked up grill, weird face.

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17
Q

What are some other signs and symptoms of beta-thal?

A
  1. Significant hepatosplenomegaly
  2. Hemachromatosis (from the hemolytic anemia)
  3. Ulcers on legs
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18
Q

What must be given in conjunction with transfusions for a beta-thal patient?

A

Iron chelation therapy to prevent iron overload.

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19
Q

Is there a physiologic mechanism for getting rid of excess iron?

A

No. Reason why iron absorption is so regulated.

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20
Q

What are the 2 causes of iron overload in beta-thal patients?

A
  1. Repeated transfusions

2. Increased iron absorption

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21
Q

Why is there an increase in iron absorption in beta-thal patients?

A

The decrease in RBCs sends a hypoxia signal to the bone marrow telling it to expand. Thus, iron absorption is increased to fuel this BM expansion (via decreased hepcidin).

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22
Q

How can you reduce the thrombotic complications in beta-thal patients?

A

Transfusions. However, more transfusions lead to increased iron loading.

23
Q

Why are there problems with endocrine organs in beta-thal patients?

A

Iron deposition causes organ damage. Hypogonadism and pituitary insufficiency.

24
Q

What are the 3 causes of osteopenia in beta-thal patients?

A
  1. Bone marrow expansion
  2. Endocrine dysfunction
  3. Iron chelators
25
Q

What is the difference between B0 and B+ thalassemias?

A

B0: no beta chains at all

B+: few beta chains expressed thus some Hgb A

26
Q

What is basophilic stippling?

A

RBCs on PBS show blue dots. The blue dots are RNA that hasn’t been degraded.

27
Q

What are the 6 diseases in which basophilic stippling is seen?

A
  1. Thalassemia trait and major
  2. Hemolytic anemia
  3. Myelodysplastic syndrome/sideroblastic anemia
  4. Megaloblastic anemia
  5. Pyrimidine 5’ nucleotidase deficiency
  6. Heavy metal poisoning: lead, zinc, arsenic, silver, mercury
28
Q

What are 5 things used in the diagnosis of beta-thal?

A
  1. Family Hx
  2. CBC
  3. Blood smear
  4. Physical exam
  5. HPLC or Hgb electrophoresis
29
Q

Can HPLC of hemoglobin be used to diagnose alpha-thal?

A

No. Those hemoglobins will not be picked up.

30
Q

What is used to diagnose alpha-thal if the mutation is known?

A

PCR

31
Q

What is used to diagnose alpha-thal if the mutation is unknown?

A

Restricted fragment length polymorphism analysis

32
Q

For which thalassemia patients are BM transplants recommended?

A

Nobody effing knows. Deal with it. Suggested for beta-thal majors early in the course of the disease.

33
Q

What are the 3 prognostic indicators for a BM transplant in thalassemia patients?

A
  1. Portal fibrosis
  2. Hepatomegaly
  3. Inadequate chelation
34
Q

What is Hereditary Persistence of Fetal Hemoglobin?

A

Big decrease in beta globin synthesis. There’s an increase in gamma chain synthesis to compensate thus Hgb F is formed. HPFH may result from a co-deletion of delta and beta genes.

35
Q

What is Hemoglobin E disease caused by?

A

Homozyguos point mutations of Glu26Lys on beta globin gene produces an unstable mRNA.

36
Q

Patients with Hemoglobin E disease will clinically resemble patients with which thalassemia?

A

Beta-thal minor

37
Q

What is E/Beta-thalassemia?

A

Patient has one beta globin gene carrying a beta-thalassemia gene and one carrying the Hemoglobin E point mutation.

38
Q

Is E/Beta-thal worse or better than Hemoglobin E disease?

A

Better usually. Clinically will resemble thalassemia minor or intermediate depending on the beta-thal mutation present.

39
Q

On electrophoresis or HPLC, Hgb E moves in the same location as what other hemoglobin?

A

Hgb A2

40
Q

What patient populations is Hemoglobin E and E/Beta-thal diseases most common in?

A

Southeast Asians. 1/4 Cambodian births. 1/9 Thai/Laotian births. Very common in US immigrant families.

41
Q

What is Hemoglobin Lepore disease?

A

Patient has normal alpha chains but a delta/beta hybrid fusion chain. This results in a drastic reduction in the non alpha chains causing a thalassemia intermediate to major phenotype in the clinic (in homozygotes).

42
Q

What is Hemoglobin S/Beta-thal disease?

A

Patients have sickle cell hemoglobin and a beta-thal gene.

43
Q

How do you make the diagnosis of Hgb S/beta-thal?

A

HPLC. Note: these patients do not have Hgb A.

44
Q

How many copies of the alpha globin gene are there?

A

4

45
Q

What causes Alpha-Thalassemia?

A

Any combination of alpha globin gene deletions.

46
Q

What are the 4 types of alpha-thal?

A
  1. Hgb Bart’s: all 4 genes lost
  2. Hgb H: 3 genes lost
  3. Alpha-thal Trait: 2 genes lost
  4. Silent carrier: 1 gene lost
47
Q

Loss of all 4 alpha globin genes results in what?

A

Death. This is Hgb Bart’s (4 gamma chains) and the fetus dies in utero. Also known as hydrops fetalis. At least one alpha globin gene is required for life.

48
Q

What is the pathophysiology of Hgb H?

A

Precipitation of beta globin tetramers as red cells age. Decreased RBC deformability leads to hemolysis. Hgb H has very high oxygen affinity and won’t unload oxygen in the tissues. Hypersplenism (10%). Leg ulcers. Gallstones. Pts rarely need transfusions or splenectomy. Rare iron overload.

49
Q

Red cells in alpha-thal silent carriers show what?

A

Normal to microcytic with minor anemia. Also, globin chain synthesis ratio of alpha:beta is 0.8-0.9.

50
Q

Red cells of alpha-thal trait patients show what?

A

Microcytic RBC indices. Normal or mild anemia. Globin synthesis ratio of alpha:beta is 0.7-0.8.

51
Q

T or F. Alpha-thal patients show lots of target cells in their PBS but these target cells are not specific for alpha-thal.

A

T: target cells are seen in other diseases too.

52
Q

What is Hemoglobin Constant Spring?

A

Single base substitution in the terminal codon of the alpha chain causing the mRNA to copy another 31 amino acids yielding an unstable mRNA. This leads to a significant decrease in the translation of the alpha globin gene.

53
Q

Patients that are homozygous for Hemoglobin Constant Spring clinically resemble patients with what type of alpha-thal?

A

Moderately severe alpha-thal

54
Q

In what patient population is Hemoglobin Constant Spring most common?

A

Southeast Asians

Heme (38 decks)

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