Test 5 Review sheet Flashcards
What type of effects/defects are present in qualitative hemoglobinopathies?
Structural defects
What condition is the most common form of hemoglobinopathies?
Sickle cell diseases
What is Vasoocclusive event
hallmark features of sickle cell disease, accounting for most hospital and emergency department visits
What ethnic group doesn’t express sickle cell diseases?
Scandinavia
Factors that make blood more viscous?
when polymers are formed and sickle cells are created
What is the effect of blood viscosity
reduced blood flow
How does blood become acidic?
prolongs exposure of the sickle cells to a hypoxic environment (decreased oxygen tension)
What occurs post-reduction of pH?
reduction in pH occurs and 2,3-biphosphoglycerate levels
Characterize sickle cell crisis in a blood smear
target cells, Howell-Jolly bodies, and an elevated white count (leukocytosis)
What confers resistance against P. Falciparum?
Sickle cell trait (heterozygosity for hemoglobin S [Hb S])
Where is this abnormal hemoglobin prevelant?
areas where this form of malaria is endemic
What globin genes are abnormal in homozygous Hb S?
Beta-globin genes are abnormal in homozygous Hb S. Hb A is not present unless the patient has received a red cell transfusion
Characterize Hb S to Hb A
Hb S is less soluble than normal Hb A, the reticulocyte count is elevated, and patients usually have a high Hb F
What is the tube solubility test of Sickle cell trait and Hb SS
The tube solubility test is positive
How can you differentiate b/n sickle cell trait and sickle cell anemia?
hemoglobin electrophoresis is the best test to differentiate the 2
. Sickle cell trait should have roughly 40% Hb S and 55% Hb A
sickle cell anemia should have predominantly Hb S with a variably increased Hb F and no Hb A
What other hemoglobin can appear on an alkaline hemoglobin electrophoresis?
Hb D
What would precipitate sickling of sickle cell anemia?
Hb S forms insoluble polymers when the oxygen saturation is low
What red cell morphology is present in sickle cell trait?
Target cells are present
What conditions show target cells? what conditions don’t?
They are present in Hb C, Hb E, and sickle cell. not seen in hereditary spherocytosis
The presence of what hemoglobin gives a positive tube solubility?
presence of Hb S
What hemoglobin type is elevated in Hb M?
Methemoglobin is elevated, 30% to 50% methemoglobin (Fe3+)
What may be present but not visible in Hb M?
Heinz bodies may be present, but they are not visible with a Wright stain
How is methemoglobin formed?
The amino acid substitutions found in the various Hb Ms cause heme iron to autooxidize, forming methemoglobin
How are Heinz bodies formed?
when hemoglobin is unstable and precipitates
What occurs during hemoglobin O2 high affinity?
less oxygen is released to tissue, leads to increase erythropoietin and make more red cells
Characterize point mutation
Replacement of one nucleotide in the normal gene with a different nucleotide
How can point mutation affect the protein’s function?
results in a different amino acid and can affect the protein’s function
Which hemoglobin are seen on cellulose acetate?
Hb S, Hb A, Hb F, and Hb A2
Where do you see Hb A?
transfused red cells
What are Hb A2 and F
normal hemoglobins
Where do you see Hb S
patients with homozygous Hb S
In what ethnicity can you find Hb E?
Southeast Asian populations
What are the lab results for Hb E?
migrates with Hb C on cellulose acetate alkaline electrophoresis.
The MCV is low and target cells are present in this trait
Because Hb A is also present, this patient probably has Hb E trait
What is thalassemia?
a varied group of disorders in which the synthesis of a normal globin chain is reduced or absent.
globin chains that are made are normal in amino acid structure
What are the concentrations of hemoglobins and what kind of globin chains are they made of?
Hb A: 96%, made of a2b2
Hb A2: 2%, made of a2d2
Hb F: 2%, a2g2
What globin chains is deficient/absent in beta thalassemia?
Beta globin chain is decreased to absent
What globin chain is normal in beta thalassemia?
alpha globin chain synthesis is normal
What population doesn’t require beta chains?
Infants up until approximately 6 months of age have an elevated Hb F that does not require beta chains
What is the primary mechanism that leads to anemia in thalassemia?
An imbalance exists in the rate of globin chain synthesis in the thalassemias
what damages the red cell?
A build-up of the globin chain is produced in excess
Characterize the bone marrow in thalassemia
Erythroid hyperplasia is present
What group of disorders are thalassemia?
a heterogeneous group of disorders that range from asymptomatic (benign) to death (incompatible with life)
State the morphology of RBCs in beta thalassemia major and minor
Minor: Basophilic stippling is seen in red cell
Major: Microcytes, hypochromia, and target cells (however present in minor as well)
What can differentiate beta thalassemia major and minor?
Clinical findings, hemoglobin concentration, and presence of Hb A
What is the primary hemoglobin in homozygous beta-thalassemia?
Hb F, with the remainder being Hb A2.
What hemoglobin is not present in homozygous beta-thalassemia?
Hb A exists, because no beta globin chains are made
What cannot be produced with missing alpha globin chains?
Hb F
What hemoglobin is present at birth in all forms of alpha thalassemia?
Barts (gamma 4) hemoglobin is present at birth
What is not present in all forms of alpha thalassemia?
Hb H inclusions, anemia, and microcytic red cells
How does hemoglobin H disease occur?
three genes are missing for alpha globin chain synthesis
excess of beta chains (b4), which is named Hb H, is present and easily detectable
What kind of anemia is present with Hb H disease?
mild to moderate anemia
In what ethnicity is Hb H disease prevelent?
Asian ethnicity
What hemoglobin require alpha chains?
All normal hemoglobins (A, A2, and F)
What is the predominant hemoglobin in the uterus?
the predominant hemoglobin will be Hb Barts (g4)
Characterize Hb Barts?
a high-oxygen-affinity hemoglobin and thus is not effective in reversible oxygen transport
What is the predominant hemoglobin up until the 3rd trimester?
Hb Portland is the primary hemoglobin
Characterize a patient with hemoglobinopathy for Hb S?
patient will not have any normal beta chains to combine with alpha chains and form Hb A
patient will have primarily Hb S, with an elevated Hb F, which is the same pattern seen in homozygous Hb S (i.e., sickle cell anemia)
red cells will be microcytic
What tests are useful for differentiating thalassemia?
Hemoglobin electrophoresis
CBC results and clinical findings (could vary)
What is the CBC result for a thalassemia trait?
The red blood cell (RBC) count is relatively high with a low MCV in thalassemia trait
What is the iron deficiency result for a thalassemia trait?
MCV can be low, but the red count is also low
Characterize Hb Barts
composed of four gamma chains
It is present at birth in all forms of alpha-thalassemia, even the silent carrier state (one gene deletion)
The Beta+ gene locus decreases what?
beta Globin chain synthesis is decreased
What is the treatment for patients with beta thalassemia major?
massive red cell transfusion therapy
What is the consequence for treatment of beta thalassemia major?
build up of iron in the body from all the transfused RBCs because the body has no mechanism for excreting iron
Characterize Hb Lepore
delta-beta fusion globin chain with decreased synthesis of the chain
Heterozygotes have a clinical course similar to that of beta-thalassemia minor.
In which ethnicity is Hb E prevalent?
Southeast Asia
Why is seperating Hb A2 and Hb F important
important to do when working up patients with possible thalassemic syndromes
What test is able to separate and quantify Hb A2 and Hb F?
High-performance liquid chromatography
