John Binstead, 27 years old, has noticed that his urine was cola-colored in the morning for...
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John Binstead, 27 years old, has noticed that his urine was cola-colored in the morning for the past 5 days, and today he experienced a sudden onset of severe abdominal pain. Physical exam, blood tests, and urine analysis show that John is anemic as the result of intravascular hemolysis. A Coombs test is nega- tive, ruling out autoimmune hemolytic anemia. Flow cytometric analysis of peripheral blood cells for CD235A (glycophorin A, present on erythroid precursors and mature red blood cells) together with CD55 (decay-accelerating factor) and CD59 (pro- tectin) reveals the absence of CD55 and CD59 on 54% of his red blood cells. Molecùlar analysis confirms a defective PIGA gene, which encodes the protein phosphatidylinositol glycan class A, which is involved in producing glycophosphatidylinositol anchors for many different proteins, including CD55 and CD59. John is diagnosed with paroxysmal nocturnal hemoglobinuria. A long-term treatment regimen including the administration of intravenous eculizumab, an anti-C5 humanized monoclonal antibody, is recommended. Which of the following provides the rationale for selecting eculizumab for the long-term manage- ment of John's condition? a. The inhibition of anaphylatoxins such as C5 decreases the inflammation that is responsible for hemolytic anemia. b. By blocking the activity of C5, the early events of complement will not be able to produce a functional C5 convertase. c. GPI anchors will form correctly if C5 is inhibited. d. A defect in CD59 function renders red blood cells especially susceptible to lysis if the membrane-attack complex is able to form. e. None of the above. John Binstead, 27 years old, has noticed that his urine was cola-colored in the morning for the past 5 days, and today he experienced a sudden onset of severe abdominal pain. Physical exam, blood tests, and urine analysis show that John is anemic as the result of intravascular hemolysis. A Coombs test is nega- tive, ruling out autoimmune hemolytic anemia. Flow cytometric analysis of peripheral blood cells for CD235A (glycophorin A, present on erythroid precursors and mature red blood cells) together with CD55 (decay-accelerating factor) and CD59 (pro- tectin) reveals the absence of CD55 and CD59 on 54% of his red blood cells. Molecùlar analysis confirms a defective PIGA gene, which encodes the protein phosphatidylinositol glycan class A, which is involved in producing glycophosphatidylinositol anchors for many different proteins, including CD55 and CD59. John is diagnosed with paroxysmal nocturnal hemoglobinuria. A long-term treatment regimen including the administration of intravenous eculizumab, an anti-C5 humanized monoclonal antibody, is recommended. Which of the following provides the rationale for selecting eculizumab for the long-term manage- ment of John's condition? a. The inhibition of anaphylatoxins such as C5 decreases the inflammation that is responsible for hemolytic anemia. b. By blocking the activity of C5, the early events of complement will not be able to produce a functional C5 convertase. c. GPI anchors will form correctly if C5 is inhibited. d. A defect in CD59 function renders red blood cells especially susceptible to lysis if the membrane-attack complex is able to form. e. None of the above.
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paroxysmal nocturnal hemoglobinuria is a rare blood disease that affects red blood cellsRBC In this ... View the full answer
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