hemoglobinopathies

Question 1

what type of inheritance pattern is sickle cell anemia?

Answer 1

autosomal recessive disorder

Question 2

what are sickle cells

Answer 2

deoxygenated hemoglobin that forms long polymers
-block vessels causing pain crises and tissue infarction especially the marrow and spleen

Question 3

what causes moderate to severe hemolytic anemia?

Answer 3

repeated sickling crises

Question 4

describe normal adult hemoglobin

Answer 4

> 95% HbA
<4% HbA2
<1% fetal hemoglobin

Question 5

HbA

Answer 5

a2B2

Question 6

HbA2

Answer 6

a2δ2

Question 7

HbF

Answer 7

a2Y2

Question 8

in sickle cell disease, B-globin chain has a point mutation at the 6th codon that causes what change?

Answer 8

glutamate to valine

Question 9

sickle cell disease vs sickle cell trait

Answer 9

disease is homozygous-symptomatic
trait is heterozygous, asymptomatic

Question 10

what percent of Africans are heterozygous for HbS?

Answer 10

up to 30%

Question 10

what does the sickle cell trait protect from?

Answer 10

malaria falciparum

Question 11

what percentage of African Americans have sickle cell trait?

Answer 11

8-10%

Question 12

what percentage of African Americans have sickle cell disease?

Answer 12

0.17%

Question 13

what are the complications that arise from vaso-occlusive crisis?

Answer 13

-pain crisis
-chronic hypoxia
-infarction (tissue death bc of lack of blood)
-acute chest syndrome-lung infection
-stroke
-sequestration crisis- in spleen of children
-aplastic crisis - parvovirus B19 (body stops making blood cells)

Question 14

what are the clinical course that can cause vaso-occlusive complications?

Answer 14

-genetic
-cigarette smoke, respiratory infection, hydration, high altitude

Question 15

at what age does complete splenic autoinfarction occur in sickle cell disease patients?

Answer 15

by age 20

Question 16

what type of infections are SCD patients susceptible to?

Answer 16

encapsulated organisms bc the spleen is impaired and can’t remove them

Question 17

Sickledex test

Answer 17

-screening test for sickle cell anemia
-mix blood with matebodulfite (reducing agent)—>sickling
-does not distinguish disease from trait

Question 18

why can you not see sickle cell disease symptoms until after 6 months

Answer 18

HbF inhibits HbS polymerization

Question 19

Hydroxyurea

Answer 19

-increases HbF
-anti-inflammatory agent
-increases red cell volume
-produces NO

Question 20

what is the survival rate with SCD

Answer 20

90% survive to age 20 and ~50% survive past age 50

Question 21

what is the mutation in hemoglobin C disease

Answer 21

glutamate to lysine

Question 22

symptoms of Hemoglobin C disease

Answer 22

-mild hemolytic anemia
-resistance to malaria
-rare

Question 23

hemoglobin C trait

Answer 23

-HbC/HbA
-2-3% if African Americans, asymptomatic

Question 24

hemoglobin C disease

Answer 24

HbCC 0.017% have it

Question 25

HbSC disease

Answer 25

-0.08% -can have pain crises but less severe than SS disease

Question 26

which hemoglobin resembles the washington monument

Answer 26

HbC

Question 27

Thalassemia etiology

Answer 27

-low intracellular Hb, low MCV and MCH -dehydration and excess membrane and folding -ineffective erythropoiesis/premature destruction of marrow erythroblasts -hemolysis in spleen -resistance to malaria falciparum -mediterranean countries, africa, and se asia

Question 28

B0-thalassemia

Answer 28

absence of B globin chains

Question 29

B+-thalassemia

Answer 29

reduced B-globin chains

Question 30

what are the 3 classes of B-thalassemia mutations

Answer 30

-chain terminator B0 -promoter region B+ -splicing B+

Question 31

Beta thalassemia major

Answer 31

-rare, homozygous -B0/B0, B0/B+, B+/B+ -anemia begins 6-9 months of age

Question 32

morphologic features of B thalassemia major

Answer 32

-decreased MCV and MCHC -anisocytosis and poikilocytosis -target cells, basophilic stippling, and fragmented RBCs -relatively mild reticulocytosis

Question 33

what do target cells look like?

Answer 33

red blood cells that have a redistribution of hemoglobin, which causes a pale region to separate the redistribution. They appear as thin cups in three dimensions

Question 34

what does Beta thalassemia major look like clinically?

Answer 34

-growth retardation and decreased lifespan -impaired bone growth -hepatosplenomegaly -blood transfusions help survival, anemia, and bony abnormalities -cardiac disease from secondary hemochromatosis -bone marrow transplantation -prenatal diagnosis

Question 35

B thalassemia minor

Answer 35

-more common -heterozygous (B+/B or B0/B) -anemia is less severe, often asymptomatic -morphologic features milder -HbA2 and HbF elevated

Question 36

what can not be treated with iron due to overload?

Answer 36

thalassemia

Question 37

α-thalassemia

Answer 37

-impaired synthesis of α-globin chains -decreased normal hemoglobin -excess unpaired chains: beta, gamma, delta -Hb Barts-newborns-Y4 tetramera -hemolysis and ineffective erythropoiesis -less severe than B-thalassemia

Question 38

most common mutation in α-thalassemia

Answer 38

deletion of α-globin genes

Question 39

1 α-thalassemia mutation

Answer 39

silent carrier state

Question 40

2 α-thalassemia mutations

Answer 40

-trait -clinically similar to B-thalassemia minor -asymptomatic -(α/α -/-) Asian type, cis, offspring at risk for HbH disease or hydrops fetalis -(a/- a/-) African type, trans

Question 41

3 α-thalassemia mutations

Answer 41

-HgH disease -mostly Asian -high affinity for O2 -HgH oxidation---->insoluble inclusions--->extravascular hemolysis -moderately severe

Question 42

4 α-thalassemia mutations

Answer 42

-Hydrops fetalis, Hb Barts -excess y-globulin chains -ineffective O2 delivery -early survival due to zeta chains that from function Hb tetramers -fetal distress in third semester -severe pallor, generalized edema, and massive hepatosplenomegaly -intrauterine transfusion

Question 43

what does a CBC of a patient with HbH disease show?

Answer 43

-elevated red blood cell count -low hematocrit -low MCV

Question 44

how is B thalassemia diagnosed

Answer 44

-gel electrophoresis, or HPLC -elevated Hgb A2 -HbF normal or elevated -same CBC as alpha

Question 45

how is α-thalassemia diagnosed

Answer 45

-elevated red blood cells -decreased MCV and MCH