Hemolytic Anemias

Globin Deficiencies

100

Which type of mutations are associated with alpha & beta thalassemias? What is the net result in each?

Alpha thalassemia: due to gene deletion. Beta thalassemia: due to gene mutations (point mutations in promoter or splicing sites) Net result= reduced synthesis of globin chains

200

In alpha thalassemia with 3 gene deletions, what type of hemoglobin is found upon electrophoresis?

Hemoglobin H

300

When does beta-thalassemia major begin presenting/becoming symptomatic?

6 months after birth

400

Describe the microscopic cell findings in a person with beta-thalassemia major.

Increased reticulocyte count, Howell-jolly bodies, Nucleated RBCs, Target cells, Teardrop cells

Immune Hemolytic Anemia

100

Fill in the blank: Immune hemolytic anemias are a group of __________ hemolytic anemias with _________ or __________ hemolysis.

Extrinsic, intravascular, extravascular

200

In the autoimmune type of hemolytic anemia, describe the pathogenesis of hemolytic anemia produced by warm antibodies?

-IgG binds RBCs in the warm temperature of the central body -The portion of the RBC membrane that’s coated with antibody is consumed by splenic macrophages. Spherocytes result (due to loss of membrane) -If entire RBC is coated with IgG, it is completely destroyed by splenic macrophages. Extravascular hemolysis results

300

List the associations of IgG and IgM-mediated disease.

IgG-Mediated Disease: o SLE (most common cause) o Chronic Lymphocytic Leukemia (CLL) o Drugs (penicillin, cephalosporins); there are 2 ways drugs may cause hemolytic anemia: Drug- induced production of autoantibodies = a-methyldopa Drug attaching directly to RBC membrane with subsequent binding of Ab to the drug-membrane complex = penicillin IgM-Mediated Disease: o Mycoplasma pneumoniae o Infectious mononucleosis

400

Describe the difference between the direct and indirect Coombs test.

In the direct test, patient’s RBCs are used; in the indirect test, RBCs foreign to the patient (i.e., test RBCs) are used.

Membrane Defects

100

Mutations occur most often in these three proteins in hereditary spherocytosis.

Ankyrin, band 3.1, and spectrin

200

Mutations occur most often in these three proteins in hereditary elliptocytosis.

spectrin, glycophorin C or band 4.1

300

Describe spherocytes and how they can be used to make a sure diagnosis of spherocytosis.

Dark red (hyperchromatic) RBCs that lack the central pallor of nl RBCs They have increased osmotic fragility when placed in hypotonic salt solution.

400

What are the characteristic clinical features of spherocytosis and what mediates the most severe aplastic crisis that may complicate the clinical course of a patient with hereditary spherocytosis?

Anemia, splenomegaly, jaundice, cholelithiasis Parvovirus B19

Intrinsic Red Cell Deficiencies

100

How does G6PD deficiency cause hemolytic anemia?

G6PD deficiency impairs the regeneration of reduced glutathione. An environmental factor (drug or infection) produces oxidants, which are normally reduced by reduced glutathione, and the oxidants attack RBC components like the globin chains

200

What are the marked findings on a peripheral blood smear for G6PDD?

Heinz bodies and bite cells

300

How does pyruvate kinase deficiency cause hemolytic anemia?

-PEP cannot be converted to pyruvate to generate ATP and lactate in the pathway. -Lack of ATP disturbs the cation gradient across the RBC membrane -Loss of potassium and water from RBC -Cell dehydration, contraction, and crenation

400

What is unique about paroxysmal nocturnal hemoglobinuria as compared to the other causes of hemolytic anemia?

It stems from acquired mutations in gene PIGA (synthesis of phosphatidylinositol glycan) in an early myeloid progenitor cell