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Hemoglobinopathies - Zaman

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Quantitative A2
TEST TO ALWAYS DO FOR THALASSEMIA?
Delta and Alpha
Hb A2 has ____ and ____ genes
NORMAL
Thal minor looks ____ on a smear.
a-thalassemia; 3
HbH disease is a form of ____; ___ genes affected
SS
Hemoglobin _____ demonstrate the full manifestation of SCD.
1
silent carrier alpha thalassemia = ___ genes affected
many; less transcription; Cooley anemia (B thalassemia major)
Mutations of B chain - ____ different ones; small changes lead to? Big changes lead to?
is there thalassemia minor of B chain!! (Test)
A2 increase in hb = ask what?
hepatosplenomegaly
Extramedullary hematopoieses leads to?
some resistance to malaria
Heterozygosity for HbS can offer?
MCV, RDW, H, Barts Hb
Alpha Thalassemia - Low ____, normal ____, HB_ and ____ hemoglobin
infarctions of bones and organs, severe pain in chest, abdomen and bones, more susceptible to e-coli, aplastic anemia (bone marrow can't compensate for the chronic blood loss)
What are the symptoms of SCD?
no severe hemolytic anemias, less deformable red cells and more removal by spleen
HbC - what are the cells like?
Zeta gene, epsilon gene; most primitive form of hemoglobin
Embryonic state - what gene is expressed? What does it bind to? What does this form?
SCD PTs, MI, cardiomegaly, CHF, TIA, Strep pneumo susceptibility; decreased respiratory function, renal infarcts, priapism (prolonged erections causing ischemia), pigmented bilirubin gallstones (brown in color), salmonella, and osteomyelitis
Repeated vaso-occlusive disease commonly found in _____ patients; what does this cause?
hemolytic anemia
Sickle cell can also lead to?
Hb electrophoresis
HPLC - better than ________ but it is still the gold standard
still express B chains
Why is sickle cell a normocytic anemia?
B thal minor, A thal, Fe deficiencies
If MCH is < 27 test for _____ and < 25 test for ____ (wont see this in ___)
HbA2 and HbF have to kick in to make up for the lack of oxygen
Disorder with NO HbA, what happens?
normocytic or macrocytic anemia
SCD blood smear?
change genetic make-up and produce normal B chains
Give stem cells to do what?
broader
Alpha thal = _____ symptoms
you can function normally w/ 1/2 HbA
Why don't heterozygous SCD pts have symptoms?
1/2 will be HbS and the other half will be HbA
Heterozygous for SCD?
valine substituted for glutamic acid in 6th position of B-chain (lysine is substituted in HbC disease)
Sickle Cell Disease - what is the mutation?
Autosplenectomy - completely infarcted because of thrombotic events
What happens to the spleen in Sickle Cell?
4; death
Homozygous a-thal - ____ genes affected; results in?
a or b chain
Thalassemia - either ___ or ____ disease
in the middle, right behind A
HbA always migrates where? S?
look for sickle cell trait
Elevated LDH -->
Alkaline, A, F, SDG, CEO, H
In Hb electrophoresis, ____ pH, ___ is one band, ___ is one band, ____ is one, ____ is one, and ___ is one band
almost none - 90% HbC
HbA present in HbC disease?
young children; poling of RBC'S in the spleen; shock
Who does sequesteration crisis affect? What does it cause? What is the final effect?
a chain and b chain
What is adult hemoglobin composed of?
the type of hemoglobin required to survive in utero
What is HbF
they can't produce HbA and begin producing HbS - severe symptoms
What happens later in life for SCD patients?
HbS is worst, HbE is least damaging
HbS, HbC, HbE - least to most severe?
2
Alpha Thalassemia trait = ___ genes affected
pre-op (hypoxic environment there)
______ screening is very important if you suspect SCD.
decreased gene transcription and unstable mRNA
What does the mutation cause?
incompatible
Homozygous a-thal - life?
thalassemia minor; thalassemia major
dB+ = ?; dB0 = ?
MCV, RDW, stippling; reticulocytes; normal or decreased; normal or increased
Beta Thalassemia - Low _____, normal _____, basophilic _____; increased _____, TIBC is _____ or _____, bone marrow FE storage ____ or ____.
acid, s from DG and C from E
In Hb electrophoresis, ____ pH differentiates ___ from ____ and __ from __.
before 3rd decade of life
B-thal major - death?
Fe defic = no increase in HbA2; Thalassemia - DO produce A2 (B/c it affects genes)
Distinguishing point between Thal and Fe deficiency?
HbS and another abnormal hemoglobin (like HbC)
Double heterozygote genotype?
increased number of erythroid precurssor cells and expansion of marrow space - facial and cranial deformaties
Bone marrow in B-thal major?
alpha thal
Hb Bart associated with?
4; 2
As many as ____ chains can be affected (as opposed to only ____ B chains)
lysine for glutamic acid at the 6th aa on B-globin chain
HbC - mutation?
HbF; increased
What is the major Hb present in B thal? Affinity for O2?
substitution at 26th pos instead of 6th
HbE disease - difference between HbC?
high levels of hemoglobin F
Why is sickle cell disease often asymptomatic in the first several months of life?
Thal minor (beta) - also sickle cell traits can be distinguished here
Quantitative chromotography for A2 tests for?
reticulocytosis
________ may be present secondary to chronic hemolysis
hypochromic and microcytic, hemolysis; hyperplasia
Homozygous B-thal - severe _______ _____ anemia with active ____.; also erythroid ____.
alpha, 16
Gene deletions on ____ chain on chromo ___.
a primitive form of A - toward the fetal b chain
What is HbA2?
disorders - like sickle cell
HbA2 is expressed with?
during deoxygenation
When are B chains damaged (polymerized) in sickle cell?

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