Thalassemia Flashcards
thalassemia produces ____ anemia
microcytic– there is a defect in hemoglobin contents of rbc, making the cell smaller.
a normal hb chain consists of:
4 heme molecules and 4 globin chains
90% of hemoglobinmocules in adults exist as:
HbA form: 2 alpha 2 beta chains. there is a small amount of HbF: 2 alpha and 2 gamma chains, and small amount of HbA2: 2 alpha and 2 delta chains.
quantitative hemoglobin disorders
quantitative: decreased/imbalanced production of globin chains:
- thalassemia alpha and beta: structurally “normal” but imbalanced
- HbE: mutation on globin chain; strucutrally abnormal. also microcytic.
Qualitative inherited disorders of hemoglobin
Mutations in globin chain altering STUCTURE AND FUNCTION: Qualitative disorders are USUALLY NORMOCYTIC because the content is the same as a normal rbc but the function is off.
Decreased solubility:
HbS, HbC
Instability: precipitation sponateneoulsy or under oxidant stress;G6PD def.
Altered oxygen affinity: familial polycythemia (increasd affinity)
HbM= unable to carry oxygen –> cyanosis.
differentiate between thalassemias
- Alpha thalassemia
- decreased synthesis of a globin chain
- Beta thalassemia
- decreased synthesis of b globin chain
normally, there are ____ alpha globin gene locis. In alpha thalassemia, there is a ____ of one or more alpha gene loci.
normally, there are 4 alpha globin gene locis. In alpha thalassemia, there is a DELETION of one or more alpha gene loci.
outline the alpha thalassemia genotypes/phenotypes
cis vs trans inheritance
when 2 mising genes ae inherited from one parents = cis
when one missing gene is inherited from each parent = trans.
CBC findings of an alpha thalassemia silent carreir and trait
silent carrier: usually normocytic and normochromic
trait: mild anemia, microcytosis, hypochromic, increased reticulocyte count, HgH ciruclating chains (4 beta globin chains making up a hemoglobin molecule and NO alpha)
what is HgH. Also, in alpha thalassemia trait, what must you watch out for?
HgH- a hemoglobin molecule comprised of 4 hbB chains and no alpha chains.
- must watch out for iron overload or mislabeling for iron deficiency. the person may present with hypochromic, target cells, microcytic RBC with anemia. might look like Fe deficiency.
CBC and clinical picture of someone with Hemoglobin H disease (A-/–)
CBC: moderate hemolytic anemia. Microcytosis. Hypochromia.
HbH circulating (no alpha chain in hemoglobin), you’d see hemogloin H bodies)
Clinical picture;
-hemolytic symptoms (splenomegaly), increased LDH, risk for iron overload, symptomatic anemia (fatigue)
outline the inheritance pattern fo alpha thalassemia, and which types are more common in africa and SE Asia
diagnosing alpha thalassemia. is ferritin elevated?
ferritin is NORMAL. beware of iron overload in patietns with alpha thalassemia
treatment for alpha thalassemias (1,2, 3, and 4 deletions)
normally, there are ___ beta globin allelles on chromosome 11. Mutations can be characterized as either:
b0 - no b globin production
• b+ - reduced b globin production
normally there’s 2 beta globin alleles
in beta thalassemia, there’s excess ___ chains
alpha chains that precipitate out as FESSA BODIES
outline the beta htalassemia genotype/phenotype
CBC and HLPC findings of beta thalassemia minor
- mild anemia, microcytosis, hypochromia, and increased HgA2 seen on HLPC (increased level ofnon-affected globins)
when would you make a diagnosis of beta thalassmia?
they are originally born healthy, because of fetal hemoglobin (A2G2), but as gamma and delta wear down, and beta is supposed to replace gamma, it becomes more and more apparent. often seen 6-12 months.
how do thalassemias result in organ damage?
the alpha/beta chain imbalances cause hemolytic anemia and icnreased RBC turnover. there is risk of
- iron overload
- ineffective erythropoises resulting in marrow expansion and bone disease, extramedullary haemopoiesis and organomegaly, peripheral hemolysis and gall stones, and hypercoagulability and vascular disease
- anemia.
all result in organ damage (heart, liver, endocrine)
treatment for beta thalassemia minor, intermedia and major
how to induce HbF. does this help with alpha or beta thalassemia?
can induce it with hydroxyurea. only helps with beta thalassemia (A2B-)because there is too much alpha and not enough beta. beta can be replaced with fetal hemoglobin to create globin chains A2G2. hydroxyurea induction of HbF would not help alpha thalassemia because alpha level is decreased and you can’t replace it with F. that might actually cause the presence of even more HbH bodies seen (rbc with no alpha Hb)
beta thalassemia major requires life long transfusion and iron chelation and monitoring for organ dysfunction. because of transfusions, what must be watched out for?
must look out for iron loading with transfusion. 1ml of packed RBC contains 1 mg of iron. No mechanism to icnrease iron excretion. Iron remains in circulation and deposites in organs.
excess iron must be removed by chelation (either parenteral or oral)
How to identify thalassemia carriers
microcytic?
if yes, is serum ferritin low or high?
if low, investigate cause of iron def. If MCV does not change after iron therapy and is still low, do Hb studies.
if serum ferritin is normal or high, do Hb studies off the bat.
how to diagnose prenatally
- molecular diagnosis of fetus using fetal cells in maternal circulation, chorionic villus sample or amniocentesis.
Outline the genotype and phenotype for HbE
HBA/E: normal heomglobin minimal microcytosis
HbE/E: mild asmptomatic anemia.
- HbE in general is not as bad as beta or alpha thalassemia, but it is still considered a QUANTITATIVE hemoglobinopathy since there is an actual decrease in proper globin synthesis.
outline the genotype and phenotype for HbC. What can it be genetically coupled with to exacerbate symptoms?
summary
things you’d see on peripheral blood smear with alpha and beta thalassemia
alpha: hypochromia, microcytosis, possible anisopoikilocytosis
beta: hypochromia, microcytosis, target cells
