What is hemoglobinopathy?
abnormality of hemoglobin (either structure or subunits)
What does the abnormal structure of Hb cause?
HbS (sickle cell anemia) | HbC | HbE
What is the mechanism of hemoglobinopathy?
when Hb polypeptide is not normal
What are the 2 things that hemoglobinopathy can be due to?
inherited abnormalities | genetic mutations
What situation causes abnormal Hb to form crystals?
low pO2
How can hemoglobinopathy lead to hemolytic anemia?
instable hemoglobin
How many alpha alleles do we have on which chromosome?
4 co-dominant alpha alleles on chromosome 16
Which alleles pair up with the alpha allele and which chromosome are they on?
beta, delta, and gamma (fetal) alleles on chromosome 11
Because the beta and alpha hemoglobin alleles are on different chromosomes, what does this say about thalassemia?
can have both alpha thal and beta thal = better so alpha and beta are more equal in number
What is the key important thing that the alpha and beta hemoglobins need to do in order to form a functioning normal hemoglobin?
pair up, equally | not equal = thalassemia
If more alpha subunits are made than beta subunits, what type of thalassemia is this?
beta thalassemia
If more beta subunits are made than alpha subunits, what type of thalassemia is this?
alpha thalassemia
What is the cause of alpha thalassemia?
deletion of one or more alpha alleles
What is the effect of 1, 2, 3, and 4 alpha allele deletions?
1 = asymptomatic normal carrier | 2 = slight anemia | 3 = severe anemia | 4 = would not make it past fetal stage
At the beta allele locus, what 4 types of beta alleles can take the place of a normal beta allele?
beta-S | beta-C | beta-E | beta-Thal
Which normal Hb is the most abundant in our circulation?
HbA1
Which type of thalassemia (alpha or beta) is more common?
alpha
What are the clinical manifestations of alpha thalassemia?
hypochromic, microcytic RBC
What is an accumulation of beta 4 in alpha thalassemia?
HbH
What is an accumulation of gamma 4 in alpha thalassemia?
Hb-Bart’s
Who is a high risk for alpha thalassemia?
asians and blacks
Which beta thalassemia type (major or minor) is more common?
minor
What is the cause of beta thalassemia?
beta-Thal gene = genetic
What is the cause of Beta Thalassemia Major?
homozygous recessive beta-Thal gene
What are the 3 other names used to call Beta Thalassemia Major?
Cooley’s Anemia | Thalassemia Major | Homozygous Beta-Thalassemia
What are the 8 clinical findings of Beta Thalassemia Major?
hypochromic, microcytic RBC | severe form hemolytic anemia = spleenomegaly | hyperplasia BM | Alpha 4 | poikilocytosis | anisocytosis | more reticulocytes | Howell-Jolly
Who is at higher risk for Beta Thalassemia Major?
white people
When can you detect symptoms for Beta Thalassemia Major in an infant and why?
6 months after birth | fetus only transcribes gamma alleles in utero … 6 months after birth = program switch from gamma to beta and detect for HbA1
What is Beta Thalassemia Minor?
heterozygous beta thalassemia with slight anemia
What are the 3 methods of treatment for Beta Thalassemia?
radiation of cells | gene therapy with viruses | stem cell therapy
Why is gene therapy using viruses risky?
viruses can cause mutations
What are the 2 methods in determining quantity?
Hb electrophoresis | chromatography
What is Hb electrophoresis?
can determine the type and quantity based on the width of the banding
What is chromatography?
rough estimate of quantity
What are the 2 possible beta thal alleles?
beta-Thal0 and beta-Thal+
What is beta-Thal0?
intermediate | total inactivation and no beta is produced
What is beta-Thal+?
some normal but slightly less than normal