Thalassemia Flashcards
What causes thalassemia?
This is due to a decreased production of globin, which is the second component required to make hemoglobin (the first component is heme). No globin = no hemoglobin.
What is the difference between thalassemia and sickle cell anemia?
Sickle cell anemia is due to a defective globin chain, thalassemia is due to a decreased synthesis of globin chains, although the chains that are made are still functional.
What makes people get thalassemia and what protection does it offer to patients?
It is an inherited mutation and it offers protection against plasmodium falciparum.
What are the two types of thalassemia?
Alpha thalassemia and Beta thalassemia.
What causes alpha thalassemia? What are the different variants of this?
It is usually a gene deletion. There are normally 4 alpha alleles in chromosome 16, 2 on each gene. Thus, there could be 1 gene deletion in which it is clinically silent. There could be 2 gene deletions, however if both the deletions occur in the same chromosome it is called cis deletion, if the two deletion occurs on opposite sides they are called trans deletion.
Which is worse, cis or trans deletions and who has the propensity to get the worse variant?
Asians tend to get the cis deletion, which is the worse variant, especially if they get 2 defective cis deletions. Trans more common in Africa, less severe.
What is HbH and when is this seen?
Hemoglobin H (HbH) is seen when there is a tetramer of beta chains that form. Normally there should be a dimer of alpha and a dimer of beta, but in the case of alpha thalassemia where 3 alpha genes are knocked out the beta forms a tetramer, which damages the RBC. It can be seen on electrophoresis.
What is Hb Barts and where is this seen?
Hb barts is a tetramer of gamma chains, seen in deletion of all 4 alpha genes. In the fetus they are supposed to have 2 alphas and 2 gammas, without the alphas the gammas form a tetramer, and this tetramer is called Hb barts. This results in death of fetus in utero, because Hb barts damages RBCs.
How does alpha and beta thalassemia differ in terms of its etiology? Where is the beta chain gene?
Alpha is due to gene deletions, beta is due to gene mutations. Beta chain is located on chromosome 11, whereas alpha chain is on chromosome 16.
What is the difference between Beta null (Beta sub 0) and Beta +?
Beta null is absent production of beta chains, Beta + is decreased production of Beta chains.
What is beta thalassemia minor?
One normal Beta and one Beta+, resulting in a clinically asymptomatic picture. Patients can have increased RBC’s with microcytic, hypochromic RBC’s and target cells on blood smears.
What would the hemoglobin electrophoresis show in a beta thalassemia minor?
Isolated and independent increase in HbA2 to 5% when normal is 2.5%. Also an increase in HbF but that’s not as important.
How does beta thalassemia major present?
These patients have Beta null Beta null, and as a fetus they are fine because fetal Hb is alpha 2 gamma 2. However over a few months they will have severe anemia because they cannot produce beta chains at all.
What are the two classic clinical features seen in patients with beta thalassemia major and why does this happen?
The crew cut hairline and the chimpmunk faces, because of the increased EPO skull and facial bones are forced to undergo hematopoeisis and as a result these deformities present. Also extramedullary hematopoeisis and HSM.
Patients with beta thalassemia major can go to aplastic crisis due to what virus?
Parovirus B19 will cause them to go aplastic crisis, in a normal patient this is not a problem but this virus shuts down RBC production. In a patient with beta thalassemia major shutting down erythropoeisis for a week will kill the pt.
