Inherited Anemias

Question 1

______ is an inherited hemoglobinopathy in which a genetic mutation leads to abnormal hemoglobin

Answer 1

Sickle Cell Disease

Question 2

Inheritence pattern of sickle cell disease

Answer 2

autosomal recessive; most common in those of african descent

Question 3

____ black children in the US are born
homozygous for Hgb S (Sickle Cell Disease)

Answer 3

1 in 400

Question 4

heterozygous for Hgb S

Answer 4

Sickle cell trait

Question 5

Pathophysiology of sickle cell disease

Answer 5

Hemoglobin S is unstable and will
polymerize in the setting of various stressors, such as hypoxic tissue and acidosis
● This polymerization leads to the
Sickle-shaped RBCs

Question 6

Sickled cells have difficulty passing through small capillaries, which can lead to ____

Answer 6

blockage and tissue necrosis

Question 7

Sickled cells are either destroyed in
peripheral circulation or by the spleen,
resulting in _____

Answer 7

Hemolytic Anemia

Question 8

Free Hgb from hemolysis causes ____

Answer 8

endothelial dysfunction, vascular injury, and pulmonary hypertension

Question 9

Early S/S sickle cell disease

Answer 9

● Early signs can include delayed growth and development, fevers, and
splenomegaly
○ Recurrent infections start occurring with hyposplenism

Question 10

When is Hgb F present?

Answer 10

first 6-12 months of life

Babies born with Sickle Cell Disease present with symptoms at about
6-12 months of age when fetal hemoglobin (Hgb F) is replaced by Hgb S

Question 11

Decreased Hgb S affinity for O2 and endovascular damage can cause
_____

Answer 11

pulmonary hypertension, CHF, etc.

Question 12

How can multi-organ failure occur in sickle cell disease?

Answer 12

Repeated episodes of vascular occlusion especially affect the heart, lungs, and liver
○ Multisystem organ failure, heart failure, stroke, and osteonecrosis are all possible and common complications

Question 13

Patients with Sickle Cell Trait do not have clinical disease unless they
are exposed to an episode of ____

Answer 13

significant hypoxia

Question 14

Clinical management if a patient presents with a sickle cell crisis

Answer 14

○ Hydration (often IV)
○ Generous analgesics
○ Oxygen supplementation
○ Hydroxyurea – reduces the frequency of painful crises, but
has some associated risks

Question 15

Patients with sickle cell disease should avoid ___ and ____

Answer 15

dehydration and hypoxia

Question 16

When _____is possible before significant
organ damage, it can cure more than 80% of patients with Sickle Cell
Anemia who have suitable matched donors

Answer 16

allogeneic Bone Marrow Transplant

Question 17

What should you recommend to patients who are heterozygous carriers (sickle cell trait)

Answer 17

Genetic counseling

Question 18

With supportive care, average life expectancy for sickle cell disease is now between ____ years of age

Answer 18

40-50

Question 19

Thalassemias are hereditary disorders characterized by ____

Answer 19

reduction in the synthesis of globin chains (alpha or beta)

Question 20

Reduced globin chain synthesis causes reduced hemoglobin creation and
a ____ because of defective
hemoglobinization of RBCs

Answer 20

hypochromic microcytic anemia

Question 21

T/F The inheritance pattern of Thalassemia is not straightforward, being autosomal
dominant for some and recessive for others

Answer 21

T

Question 22

Thalassemia overall is most common in families from ____

Answer 22

southeast Asia and China, the Mediterranean area, and those of African descent

Question 23

Alpha-Thalassemia:

Answer 23

Due to complete loss of one or more of the four
copies of the alpha-globin chain gene

Question 24

Alpha- thalassemia levels

Answer 24

○ Loss of 1 - Silent carrier (asymptomatic)
○ Loss of 2 - Alpha-Thalassemia trait (“minor-thalassemia”)
○ Loss of 3 - “Alpha 3”
■ Severe anemia with signs of hemolysis – requires treatment
○ Loss of 4 - Hydrops fetalis (death in utero)
■ No normal alpha hemoglobin is produced

Question 25

Alpha-Thalassemias are seen primarily in persons from ______

Answer 25

southeast Asia and
China, and (less commonly) in African and persons of Mediterranean origin

Question 26

Beta-Thalassemia:

Answer 26

Due to mutation of promoter sequence for beta-globin chain gene

Question 27

Depending on the type of mutation, the reduced beta-globin
synthesis results in a relative increase in proportions of ____

Answer 27

Hgb A2 and Hgb F compared to Hgb A

Question 28

Beta-Thalassemia primarily affects persons of ____

Answer 28

Mediterranean origin (such
as Italian, Greek, etc.), and to a lesser extent Asians and African

Question 29

Signs and Symptoms (for both alpha and beta thalassemia)

Answer 29

● Clinical presentation can vary significantly and depends on the severity of inherited mutations
● In more mild disease, normal symptoms of anemia may be present (may present like IDA)
● In severe disease, as seen with Alpha-3 or Beta-Major, patients can present with severe anemia, hemolysis, jaundice, hepatosplenomegaly, and significant fatigue

Question 30

Patients with mild disease (Alpha-Thalassemia Trait or
Beta-Thalassemia Minor) require ___

Answer 30

no treatment

Question 31

Patients with severe thalassemia are generally maintained on a
regular ____

Answer 31

transfusion schedule (every 2-3 weeks)

Question 32

____ is the treatment of choice for
Beta-Thalassemia Major and the only available cure for these patients

Answer 32

Allogeneic stem cell transplantation

Question 33

Thalassemia should not be treated with ____

Answer 33

iron

Question 34

Glucose-6-Phosphate Dehydrogenase is ____

Answer 34

a cytosolic enzyme that
maintains normal cellular levels of another enzyme, NADPH

Question 35

____ is necessary for
maintaining levels of Glutathione
(GSH)

Answer 35

NADPH

Question 36

GSH is an important
antioxidant capable of
_____

Answer 36

donating an electron to free
radicals

Question 37

G6PD Deficiency is an ____ condition

Answer 37

X-Linked Recessive

Question 38

It is the most common human
enzyme defect

Answer 38

G6PD deficiency

Question 39

Deficiency of G6PD in RBCs means that the cell cannot handle large
amounts of ____

Answer 39

oxidative stress

Question 40

If oxidative stress occurs, the RBCs can’t
stabilize oxidants which results in ____

Answer 40

structural damage within the cells

Question 41

Oxidative damage to the cells results in
either spontaneous RBC rupture or
removal by the spleen, causing

Answer 41

○ Heinz bodies
○ Bite/blister cells
○ Schistocytes

Question 42

G6PD deficiency results in ____

Answer 42

hemolytic anemia

Question 43

In situations of oxidative stress, the patient presents with Hemolytic
Anemia with these S/S

Answer 43

○ Fatigue
○ Jaundice
○ Dark urine

Question 44

Clinical management of G6PD deficiency

Answer 44

● Treatment generally revolves around treating the infection or removing the offending drug/food
○ No G6PD-specific treatment is necessary
● Full recovery occurs within a matter of weeks
● After recovery, the patient should focus on lifelong avoidance of know triggers