Practice Question Answers Anemia VI

Practice Question Answers

Anemia VI

© Jun Wang, MD, PhD

 

Abbreviations:

Hb: hemoglobin	HCT: hematocrit
MCV: Mean Corpuscular Volume	MCH: Mean Corpuscular Hemoglobin
RDW: Red Cell Distribution Width	TIBC: total iron binding capacity

 

1. A. This case is characterized by sudden onset of jaundice and dark urine after medication, consistent with a drug induced hemolysis, further supported by elevated indirect bilirubin and LDH, and presence of bite cells (semicircular portion loss) and blister cells (submembrane vesicle/peripheral vacuole) in peripheral blood. He has had similar episodes. These features are highly suspicious of G6PD deficiency. Eosin-5-maleimide binding assay and osmotic fragility test is used to diagnose hereditary spherocytosis. Flow-cytometry for RBC bound CD55 and CD59 is used to diagnose paroxysmal nocturnal hemoglobinuria. Hemoglobin analysis by electrophoresis of HPLC is very helpful in diagnosing hemoglobin abnormalities, including thalassemia, sickle cell anemia, HbC and HbE. Molecular test for PKLR mutation is used to diagnose pyruvate kinase deficiency. All of these conditions tend to have chronic hemolysis, instead of a sudden process.

2. A. This is a process of hemolysis and haptoglobin will be decreased after finding with free hemoglobin and removed by reticuloendothelial system. Homocysteine is high in megaloblastic anemia associated with folate or VB12 deficiencies. Iron tends may be higher in sideroblastic anemia and anemia of chronic disease, and low in iron deficiency anemia. Lead is elevated in anemia associated with lead poisoning. TIBC can be elevated in iron deficiency anemia and low in anemia of chronic disease. These four is not associated with hemolysis. 

3. A. Hemolysis results in increased indirectly bilirubin in blood, and urobilinogen in urine. Colorless urobilinogen can be oxidized to yellow urobilin, resulting in darker urine. The metabolites of antibiotics may change the color of urine. Over-concentration of urine usually results from dehydration. Urinary bladder infection or bleeding may change the color of urine to pink, if hematuria is present. While these are possible causes, the presence of hemolysis make increased urobilinogen most likely the cause.

4. D. Hemolysis in G6PD deficiency is associated with reduced NADPH production and low levels of reduced form glutathione. These abnormalities make RBCs vulnerable to oxidative stresses, commonly caused by infections, drugs and certain food. Anti-RBC antibodies cause hemolysis in immune hemolytic anemia. ATP insufficiency causes hemolysis in pyruvate kinase deficiency. Cytoskeletal abnormalities are associated with hemolysis in hereditary spherocytosis. Over activity of surface complements is seen in paroxysmal nocturnal hemoglobinuria.

5. B. Diagnosis is confirmed by enzymatic activity test of G6PD. Also see discussion of question 1. Cold agglutin disease is characterized by recurrent painful episodes of fingers and toes and bluish discoloration involving skin that are triggered by low temperature. It is caused by cold reacting auto-antibodies, primarily IgM. Hereditary spherocytosis has spherocytes. Paroxysmal nocturnal hemoglobinuria is characterized by dark urine started at night and cleared during the day. These two and pyruvate kinase deficiency have chronic hemolysis and none of these four have bite cells or blister cells.

6. C. This case is characterized by normocytic anemia with increased reticulocytes, jaundice and increased indirect bilirubin, consistent with hemolytic anemia. Bone marrow suppression can be seen in various aplastic anemia and myeloid neoplasms, and usually has low reticulocyte count. Hemoglobin abnormalities, including thalassemia, sickle cell anemia, HbC and HbE, have red cell changes, such as sickle cell, rhomboidal crystals, or target cells. Iron deficiency anemia is microcytic hypochromic anemia with reduced serum iron, ferritin, transferrin saturation and elevated TIBC, but usually does not have hemolysis. Vitamin B12 deficiency is associated with megaloblastic anemia.

7. B. Negative DAT is consistent with a non-immune hemolysis. Chronic normocytic anemia due to hemolysis with a positive family history and negative DAT and normal RBC morphology raise the concern of pyruvate kinase deficiency. Bone marrow biopsy is useful in specific diagnosis of many anemia, especially hematopoietic stem cell abnormalities, such as aplastic anemia and myeloid neoplasms. Flow-cytometry for RBC bound CD55 and CD59 is used to diagnose paroxysmal nocturnal hemoglobinuria. Hemoglobin analysis by electrophoresis of HPLC is very helpful in diagnosing hemoglobin abnormalities, including thalassemia, sickle cell anemia, HbC and HbE. Serum iron, folate and VB12 tests are used to evaluate iron deficiency anemia, sideroblastic anemia, anemia of chronic disease, and megaloblastic anemia.

8. D. Markedly reduced enzymatic activity of pyruvate kinase is consistent with pyruvate kinase deficiency, caused by PKLR mutation. Mutations of ANK1 or SPTA1 are seen in hereditary spherocytosis. Beta globin mutations can be seen in beta thalassemia, sickle cell anemia, HbC and HbE. PIGA mutation is seen in paroxysmal nocturnal hemoglobinuria.

9. A. Pyruvate kinase deficiency results in reduced ATP production in RBC, and subsequent transmembrane cation gradient and RBD dehydration and contraction. These abnormal RBCs are prone to be removed by reticuloendothelial system. Antibody against RBC surface antigens causes hemolysis in immune hemolytic anemia. Hemolysis triggered by oxidative stress is seen in G6PD deficiency. Loss of membrane elasticity can be resulted from abnormal hemoglobin, such as HbS, HbC and HbE, and spherocytosis. Precipitation of abnormal hemoglobin is associated with HbS and HbC, etc. Uninhibited complement activity is associated with loss of CD55 and CD59, in paroxysmal nocturnal hemoglobinuria.

10. D. See discussion of question 7. G6PD deficiency is characterized by sudden onset of hemolysis triggered by oxidative stress. Hereditary spherocytosis has spherocytes. Paroxysmal nocturnal hemoglobinuria is characterized by dark urine started at night and cleared during the day. Warm antibody autoimmune hemolytic anemia has positive DAT.

11. C. This case is characterized by normocytic anemia with evidence of hemolysis. Negative DAT rules out immune hemolytic anemia. Peripheral blood smear reveals the presence of spherocyte (RBC without central pallor area). These findings are consistent with hereditary spherocytosis. Eosin-5-maleimide binding assay and osmotic fragility test is used to diagnose hereditary spherocytosis. Chromosomal breakage tests and molecular tests for FANC gene mutations are used to diagnose Fanconi anemia. Enzymatic activity of G6PD is used to diagnose G6PD deficiency. Hemoglobin analysis by electrophoresis of HPLC is very helpful in diagnosing hemoglobin abnormalities, including thalassemia, sickle cell anemia, HbC and HbE. Serum iron, folate and VB12 tests are used to evaluate iron deficiency anemia, sideroblastic anemia, anemia of chronic disease, and megaloblastic anemia. Serum lead test is used to diagnose lead poisoning, that may present as a type of sideroblastic anemia.

12. B. Membrane instability is seen in hereditary spherocytosis, due to mutation of cytoskeletal components. Also see discussion of question 9.

13. C. Membrane instability in hereditary spherocytosis results in partial loss of membrane and elevated volume/membrane ratio. These changes cause loss of RBC flexibility and make them prone to be removed by reticuloendothelial system, a process of extravascular hemolysis. There is no evidence of auto-immune disorder, biliary tract obstruction, liver disease or splenic tumor in this patient.

14. E. See discussion of question 8. G-6-PD mutation is seen in G6PD deficiency.

15. B. Reduced eosin-5-maleimide binding in this clinical setting is most consistent with hereditary spherocytosis. Also see discussion of questions 7 and 10.

16. C. This case is characterized by dark urine in the morning most likely starts at night, and cleared during the day. Negative DAT ruled out immune hemolytic anemia. This is a typical presentation of paroxysmal nocturnal hemoglobinuria. It is associated with PIGA mutation and subsequent loss of CD55 and CD59 on RBC surface. Loss of CD55 and CD59 results in uninhibited complement activity that causes hemolysis. RBC without CD55 and CD59 can be detected by flow-cytometry. Enzymatic activity of G6PD is used to diagnose G6PD deficiency. Eosin-5-maleimide binding assay and osmotic fragility test is used to diagnose hereditary spherocytosis. Hemoglobin analysis by electrophoresis of HPLC is very helpful in diagnosing hemoglobin abnormalities, including thalassemia, sickle cell anemia, HbC and HbE. Molecular test for PKLR mutation is used to diagnose pyruvate kinase deficiency. Parvovirus B19 test is used to diagnose aplastic anemia associated with Parvovirus B19 infection, such as pure red cell aplasia, or aplastic crisis in sickle cell anemia.

17. C. Flow-cytometry identified RBCs without bound CD55 and CD59, confirms the diagnosis of paroxysmal nocturnal hemoglobinuria. G-6-PD mutation is seen in G6PD deficiency. RPS19 and GATA-1 mutations can be seen in pure red cell aplasia. PKLR mutation is seen in pyruvate kinase deficiency. SPTA1 mutation is seen hereditary spherocytosis.

18. E. Loss of RBC surface CD55 and CD59 in paroxysmal nocturnal hemoglobinuria results in uninhibited complement activity that causes hemolysis. Also see discussion of question 9.

19. D. Uninhibited complement activity in paroxysmal nocturnal hemoglobinuria may affect hematopoietic stem cells and causes pancytopenia. Chronic blood loss may cause iron deficiency anemia, but usually does not change WBC and platelet counts. Erythroid maturation arrest is seen in pure red cell aplasia. Hemoglobin beta gene deletion is associated with beta thalassemia. Myelofibrosis may cause aplastic anemia, but usually does not have hemolysis.

20. C. Paroxysmal nocturnal hemoglobinuria causes depletion of nitric oxide by free hemoglobin, and subsequently causes smooth muscle dystonia, presenting as headache, abdominal pain, etc. There is no evidence of bacterial or viral infection in this patient. RBC aggregates associated painful crisis is seen in sickle cell anemia. Tissue hypoxia is common in any patient with anemia, but it has no know specific association with headache or abdominal pain.

21. D. See discussion of question 16. Fanconi anemia is a type of aplastic anemia, commonly has birth defects such as musculoskeletal abnormalities and abnormal pigmentation of skin. G6PD deficiency is characterized by sudden onset of hemolysis triggered by oxidative stress. Hereditary spherocytosis has spherocytes. Pyruvate kinase deficiency tends to have chronic clinical course. Warm antibody autoimmune hemolytic anemia has positive DAT. These five have normal quantity of CD55 and CD59 on RBC surface.

 

 

 

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