Thalassemia Flashcards
Hemoglobin is made up of?
an iron containing hem ring surrounded by 4 globin chains, 2 alpha and 2 non-alpha
Normal adult HB consists of?
2 alpha and 2 beta chains
Normal fetal HB consists of?
2 alpha and 2 gamma chains
HB A2 has?
2 alpha and 2 delta chains
Fetal HB transition occurs?
transition from gamma to beta starts before birth, but at birth HB F is 80% and HB A is 20%. By 6 months, most infants have transitioned to mostly HBA
Genetics of Alpha Thal?
-Autosomal recessive
-quantitative defect of alpha globin chain, leads to excess B globin chains
-Alpha chain synthesis controlled by 2 genes on each chromosome 16
One gene deletion in Alpha thal?
silent carrier, asymptomatic, but needs preconception counselling
-may have MCV may be slightly lower
Two gene deletion in Alpha Thal?
-Trait/minor
-mild microcytosis, erythrocytosis, hypochromia ,but not usually anemia
Three gene deletion in Alpha Thal?
-HB H disease or intermedia
-results in significant HB H production, which consists of 4 beta chains
-results in microcytic anemia, hemolysis and splenomegaly
-not typically transfused unless growth failure
4 gene deletion in Alpha Thal?
-HB Barts with 4 gamma chains
-usually results in non-immune hydrops fetalis, unless intrauterine transfusions
Beta Thalassemia ?
Absent/deficient beta globin chains leading to excess alpha globin chains
Genetics of Beta Thalassemia?
-Beta globin synthesis is controlled by one gene on each chromosome 11.
-Autosomal recessive
-occurs d/t one of the 200 point mutations on chromosome 11, and rarely as deletion
-Beta chain production can be normal or near absent, leading to varying degrees of excess alpha vs beta production
Beta thalassemia Major or Cooley’s anemia?
Results from absent/reduced production of 2 beta globin genes, and excess alpha globin chains
-asymptomatic at birth until 6 months of life because sufficient HB F production
-splenomegaly, anemia, growth issues, boney changes, hemolysis, jaundice
-requires lifelong transfusions
One gene defect in Beta Thal leads to?
Beta thalassemia trait, which is asymptomatic, but can have microcytosis and mild anemia
Genetics of Beta Thalassemia intermedia?
-results from mildly reduced beta chains in both genes
-less severe than Major, but may require intermittent transfusions during periods of growth
Alpha thal HB H-Constant Spring?
-elongated Alpha globin chain d/t termination codon mutation
-one parent has HB H constant spring and silent carrier; the other parent has alpha trait
-Phenotype is that these patients are more affected clinically than HB H
Beta Thal can have a coexisting Hemoglobinopathy resulting in?
Decreased quality of Beta globin chain (HB S), AND decreased quantity from the thalassemia (HB S/beta thal zero or plus)
Those with Thalassemia have microcytic anemia; what are the DD’s?
IDA, ACD, lead poisoning, Sideroblastic anemia
What is the Mentzer index?
For Children, what is Mentzer index in Thal vs IDA?
-MVC/RBC
-less than 13=Thal
->13=IDA
-13=uncertain
MCV in Thal VS IDA
-Thal= <75
-IDA= rarely <80 unless HCT is <30
RDW in
Thal?
IDA?
Sideroblastic?
-thal=low in 50%
-IDA=elevated in 90%
-Sideroblastic=almost always elevated
-Therefore, normal RDW usually thalassemia, but elevated RDW cannot distinguish between IDA and sider
BEST screening test for IDA in absence of inflammation?
Serum ferritin
-may need TIBC and iron and transferrin for inflammatory states as ferritin may be falsely elevated
sideroblastic anemia excluded through which test(s)?
-peripheral smear and rarely Bone marrow aspirate
How to rule out lead poisoning as cause of microcytic anemia?
- serum lead level
How to rule out ACD as cause of microcytic anemia?
often normocytic, normochromic mild anemia
What is Thal still suspected despite intensive BW work up?
HB electrophoresis
What does HB electrophoresis look like for Beta Thal trait?
-reduced/absent HBA, elevated HBA2 and HBF
-BUT normal HBA2 does not rule out Beta thal trait with coexistent IDA, as IDA lowers HBA2 to normal level
What does HB electrophoresis look like in adults with Alpha trait?
Normal
If an infant has HB H or HB Barts on HB electrophoresis, they have?
Alpha Thalassemia
What does the diagnosis of a patient with Beta Thal intermedia look like?
-with milder symptoms of microcytic anemia later in childhood/life
Complications with Beta thal major or more severe intermedia?
Overstimulation BM from ineffective erythropoesis, iron overload from blood transfusions?
Untreated infants with Beta Thal major will have?
-poor growth, boney deformities, jaundice
Consequences of iron overload with chronic transfusions in Alpha and Beta Thal major?
-mainly iron deposits in visceral organs such as liver, heart and endocrine glands
-most death secondary to cardiac complications with Iron overload
-hypogonadism and DM may occur in teens and adults
What finding most common on PE of symptomatic Thal pt?
-splenomegaly, which can lead to worsening anemia, and occasionally cause neutropenia, thrombocytopenia
-need for increased transfusions
-after splenectomy, thal pt can develop hypercoaguable state= arterial and venous thromboembolic events can be result
When do blood transfusions start in patients with Beta Thal major?
-around 6 months of age with normal nadir of HB F
-keep HBA >95 and/or to promote normal growth
Transfusions in HB H or Beta thal intermedia?
-only if clinically indicated for growth and development or if more severe phenotype ie., HB H constant spring or more severe Beta thal intermedia
Why is splenectomy generally delayed until 4 y of age?
-because of spleen’s role in clearing bacteria and preventing sepsis.
Which vaccinations required prior to splenectomy?
pneumococcal conjugate 13 valent series and pneumococcal polysaccharide 23 valent vaccine ONE Month prior to sx
Serum ferritin as a marker for iron Cardiac overload?
- ferritin can be used as a marker of iron storage.
-Ferritin <2500=improved survival
-if liver dx present, ferritin unreliable
Is folic acid supplementation indicated in pt with Thal?
What dose?
-if thal major/intermedia have a folate deficiency due to increased erythropoiesis
-1mg folic acid daily
Is HU used to treat Thal?
Yes, in cases of non-transfusion dependent Beta Thal, such as intermedia or HB E/Beta Thal who have chronic anemia and require intermittent transfusion
What are the positive effects of HU in some Beta Thal intermedia and HB E/Beta thal patients?
-positive effect on decreasing transfusion requirements EMH, ineffective erythropoiesis and decreasing spleen size
What is the percentage of responders to partial responders to HU?
~50% responders
~79% partial responders
-therefore, significant # of patients are non-repsonders
-some have increase in HB F but transfusion requirements are unchanged
