hemoglobinopathies Flashcards
what type of inheritance pattern is sickle cell anemia?
autosomal recessive disorder
what are sickle cells
deoxygenated hemoglobin that forms long polymers
-block vessels causing pain crises and tissue infarction especially the marrow and spleen
what causes moderate to severe hemolytic anemia?
repeated sickling crises
describe normal adult hemoglobin
> 95% HbA
<4% HbA2
<1% fetal hemoglobin
HbA
a2B2
HbA2
a2δ2
HbF
a2Y2
in sickle cell disease, B-globin chain has a point mutation at the 6th codon that causes what change?
glutamate to valine
sickle cell disease vs sickle cell trait
disease is homozygous-symptomatic
trait is heterozygous, asymptomatic
what percent of Africans are heterozygous for HbS?
up to 30%
what does the sickle cell trait protect from?
malaria falciparum
what percentage of African Americans have sickle cell trait?
8-10%
what percentage of African Americans have sickle cell disease?
0.17%
what are the complications that arise from vaso-occlusive crisis?
-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)
what are the clinical course that can cause vaso-occlusive complications?
-genetic
-cigarette smoke, respiratory infection, hydration, high altitude
at what age does complete splenic autoinfarction occur in sickle cell disease patients?
by age 20
what type of infections are SCD patients susceptible to?
encapsulated organisms bc the spleen is impaired and can’t remove them
Sickledex test
-screening test for sickle cell anemia
-mix blood with matebodulfite (reducing agent)—>sickling
-does not distinguish disease from trait
why can you not see sickle cell disease symptoms until after 6 months
HbF inhibits HbS polymerization
Hydroxyurea
-increases HbF
-anti-inflammatory agent
-increases red cell volume
-produces NO
what is the survival rate with SCD
90% survive to age 20 and ~50% survive past age 50
what is the mutation in hemoglobin C disease
glutamate to lysine
symptoms of Hemoglobin C disease
-mild hemolytic anemia
-resistance to malaria
-rare
hemoglobin C trait
-HbC/HbA
-2-3% if African Americans, asymptomatic
hemoglobin C disease
HbCC
0.017% have it
HbSC disease
-0.08%
-can have pain crises but less severe than SS disease
which hemoglobin resembles the washington monument
HbC
Thalassemia etiology
-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
B0-thalassemia
absence of B globin chains
B+-thalassemia
reduced B-globin chains
what are the 3 classes of B-thalassemia mutations
-chain terminator B0
-promoter region B+
-splicing B+
Beta thalassemia major
-rare, homozygous
-B0/B0, B0/B+, B+/B+
-anemia begins 6-9 months of age
morphologic features of B thalassemia major
-decreased MCV and MCHC
-anisocytosis and poikilocytosis
-target cells, basophilic stippling, and fragmented RBCs
-relatively mild reticulocytosis
what do target cells look like?
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
what does Beta thalassemia major look like clinically?
-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
B thalassemia minor
-more common
-heterozygous (B+/B or B0/B)
-anemia is less severe, often asymptomatic
-morphologic features milder
-HbA2 and HbF elevated
what can not be treated with iron due to overload?
thalassemia
α-thalassemia
-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
most common mutation in α-thalassemia
deletion of α-globin genes
1 α-thalassemia mutation
silent carrier state
2 α-thalassemia mutations
-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
3 α-thalassemia mutations
-HgH disease
-mostly Asian
-high affinity for O2
-HgH oxidation—->insoluble inclusions—>extravascular hemolysis
-moderately severe
4 α-thalassemia mutations
-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
what does a CBC of a patient with HbH disease show?
-elevated red blood cell count
-low hematocrit
-low MCV
how is B thalassemia diagnosed
-gel electrophoresis, or HPLC
-elevated Hgb A2
-HbF normal or elevated
-same CBC as alpha
how is α-thalassemia diagnosed
-elevated red blood cells
-decreased MCV and MCH
