1. What is the difference between intravascular and intrinsic hemolysis? Between extravascular and extrinsic hemolysis?
2. Would a patient with low haptoglobin, high LDH, and hemoglobinuria be most likely to have intravascular hemolysis or extravascular hemolysis?
3. Ankyrin and spectrin may be defective in which hemolytic anemia?
4. Upon entry into a cell, glucose is phosphorylated to become glucose 6-phosphate. List the 3 sepa- rate metabolic pathways it can then enter and the purpose of each pathway.
a. Glycolysis to generate energy b. Glycogenesis for storage of glucose c. HMS for generating NADPH and ribose-P
5. In glycolysis, the oxidation of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycer- ate results in the conversion of NAD to NADH. The function of the NADH is to
.
Intravascular refers to hemolysis occurring within a blood vessel and intrinsic refers to causes of hemolytic anemia due to factors in the erythrocyte. Extravascular refers to hemolysis occurring outside a blood vessel and extrinsic refers to hemolytic anemia due to factors outside the erythrocyte.
Intravascular hemolysis. Extravascular hemolysis would be characterized by high LDH and high unconjugated bilirubin.
Hereditary spherocytosis
generate ATP
Immunology , Hematology , and Oncology
6. In the hexose monophosphate shunt, the oxidation of glucose 6-phosphate by the enzyme G6PD results in the conversion of NADP to NADPH. In erythrocytes, what is the function of NADPH?
7. In which hemolytic anemia are Howell-Jolly bodies and osmotic fragility typical and erythrocytes more susceptible to oxidative stress secondary to low levels of glutathione?
8. What is the mode of inheritance of G6PD deficiency?
9. What are some precipitating factors for hemolysis in G6PD deficiency?
10. What is a Heinz body and how is it formed?
11. Why are certain drugs such as sulfa drugs not administered to an individual with G6PD deficiency?
12. Why is an individual with G6PD deficiency expected to have hemolytic anemia?
13. What glycolytic enzyme deficiency can often lead to hemolytic anemia?
Supply electrons to convert and replenish oxidized glutathione to reduced glutathione.
G6PD deficiency
X-linked recessive
Sulfonamide drugs, fava beans, antimalarials (primaquine), anti-TB drugs
A Heinz body is cross-linked, denatured, precipitated hemoglobin inside the RBC. Reactive oxygen species, especially H2O2, will oxidize the sulfhydryl groups on hemoglobin forming disulfide bridges among many hemoglobins.
Sulfa drugs, among others, can generate reactive oxygen species that can overwhelm the limited detoxifica- tion capacity of a patient’s cells.
G6PD deficiency leads to an increase in reactive oxygen species (e.g. H2O2) that cause erythrocyte lysis.
Pyruvate kinase deficiency
Hemolytic Anemia and Pathologic Red Blood Cell Forms
Immunology , Hematology , and Oncology
14. Why is an individual with pyruvate kinase deficiency expected to have hemolytic anemia?
15. How is hemolytic anemia caused by G6PD deficiency distinguished from pyruvate kinase defi- ciency?
16. What is the cause of sickle cell anemia?
17. Which virus causes aplastic crises in sickle cell patients?
18. What renal complication is characteristically associated with sickle cell anemia?
19. What can be used in sickle cell disease to increase HbF?
20. What is the biochemical defect in HbC disease?
21. Which CD marker is characteristically negative in paroxysmal nocturnal hemoglobinuria?
22. Abnormality of which RBC membrane protein causes paroxysmal nocturnal hemoglobinuria?
Pyruvate Kinase is a required step for glycolysis. One purpose of glycolysis is to generate ATP to power the active transport ion pumps. Without active ion transport membrane integrity is impaired, leading to cell lysis.
Heinz bodies are present in G6PD deficiency but not in PK deficiency.
Replacement of glutamic acid by valine in the beta chain, producing HbS
Parvovirus B19
Renal papillary necrosis
Hydroxyurea
Lysine replaces glutamic acid at position 6 of the hemoglobin chain.
CD59 is negative.
GPI protein, which normally binds to decay accelerating factor (DAF)
Immunology , Hematology , and Oncology
23. In both the innate response and the adaptive response, formation of which complement factor leads to C5 production (that in turn leads to formation of the membrane attack complex)?
24. C1 esterase inhibitor deficiency produces which disease?
25. Which of the complement deficiencies are most strongly associated with anaphylactic shock?
26. Is warm agglutinin autoimmune hemolytic anemia mediated by IgM or IgG antibodies? Cold ag- glutinin hemolytic anemia?
27. What is an autoimmune hemolytic anemia that develops when an Rh-negative mother creates anti- bodies against an Rh-positive fetus?
28. What does the direct Coombs test look for?
Indirect Coombs test?
29. Damage to RBCs during passage through narrowed vessels can produce what altered RBC form?
30. What disease is suggested by a Maltese cross appearance in erythrocytes in a peripheral smear?
C3
Hereditary angioedema
C3a and C5a
IgG mediates warm agglutinin and IgM mediates cold agglutinin.
Erythroblastosis fetalis
Direct Coombs detects IgG on RBC surfaces
indirect Coombs detects IgG in serum that binds to RBCs
Schistocytes
Babesiosis
Hemolytic Anemia and Pathologic Red Blood Cell Forms
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31. Acanthocytes are found in what disease?
32. Basophilic stippling is seen in which diseases?
33. Bite cells are seen in what disease?
34. The mechanism underlying elliptocytosis is similar to the process underlying what other erythro- cyte pathology?
35. Fragmented red blood cells are seen in which diseases?
36. Damage to a red cell by an artificial heart valve would produce what altered erythrocyte form?
37. Teardrop cells typically signal the presence of what process?
38. Target cells are found in which diseases?
39. Fill in the following table.
Disease Serum Iron Transferrin (TIBC) Ferritin
Iron deficiency Low High Low
Anemia of chronic disease Can be low Very low High
Hemochromatosis High Low High
Liver disease
Thalassemias, anemia of chronic disease, iron deficiency, and lead poisoning (TAIL)
Glucose 6 phosphate deficiency
Spherocytosis
Disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome.
Schistocyte
Bone marrow infiltration, such as by myelofibrosis.
Hemoglobin C disease, asplenia, liver disease, and the thalassemias.
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