A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 48-year-old woman comes to the physician because of a 4-month history of lightheadedness, intermittent headaches, and easy bruising. Five months ago, she was treated for an episode of thrombophlebitis. Physical examination shows multiple bruises on her limbs. Laboratory studies show a platelet count of 900,000/mm3 and elevated levels of serum lactate dehydrogenase and uric acid. Treatment with a medication is begun that is also used in the treatment of sickle cell disease. Which of the following mechanisms is most likely responsible for the beneficial effect of this drug in sickle cell disease?
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A
Inhibition of thrombocyte aggregationIncorrect. Inhibition of platelet aggregation describes aspirin's mechanism; aspirin is also used in essential thrombocythemia but is not the SCD-linked drug being asked about.
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B
Increase in circulating fetal hemoglobinCorrect. Hydroxyurea induces fetal hemoglobin (HbF) production in sickle cell disease, diluting HbS and preventing polymerization; in ET it acts as a cytoreductive ribonucleotide reductase inhibitor.
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C
Inhibition of stem cell differentiationIncorrect. Hydroxyurea inhibits DNA synthesis (ribonucleotide reductase) but does not block stem cell differentiation; the SCD benefit is HbF induction, not differentiation arrest.
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D
Restoration of the body's iron storesIncorrect. Restoration of iron stores is the mechanism of iron supplementation in iron deficiency anemia, unrelated to hydroxyurea or sickle cell disease.
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E
Activation of erythropoietin receptorsIncorrect. Activation of erythropoietin receptors describes the mechanism of EPO-stimulating agents (epoetin alfa, darbepoetin), not hydroxyurea, which acts by inhibiting ribonucleotide reductase and inducing fetal hemoglobin.
↑ Tap an answer to reveal the reasoning
Answer: B. A middle-aged woman with thrombocytosis (platelets 900,000), prior thrombosis (recent thrombophlebitis), bruising, and elevated LDH/uric acid (markers of high cell turnover) has essential thrombocythemia (or another myeloproliferative neoplasm). The treatment that overlaps with sickle cell disease management is hydroxyurea, a ribonucleotide reductase inhibitor.
In sickle cell disease, hydroxyurea's primary therapeutic mechanism is induction of fetal hemoglobin (HbF, alpha2gamma2) production. HbF does not contain beta-globin chains and therefore cannot polymerize with sickle hemoglobin (HbS). Higher HbF levels dilute HbS within red cells, raising the polymerization threshold and reducing sickling, vaso-occlusive crises, acute chest syndrome, and mortality. Hydroxyurea also modestly reduces leukocyte and reticulocyte counts (which reduces vaso-occlusive cell adhesion).
In myeloproliferative disorders, hydroxyurea's mechanism is myelosuppression via inhibition of ribonucleotide reductase (depleting dNTPs needed for DNA synthesis), thereby controlling cell counts and reducing thrombotic risk. Inhibition of thrombocyte aggregation describes aspirin (also given in ET but it is not the unique link to sickle cell). Iron stores restoration is unrelated. Stem cell differentiation inhibition would worsen the disease.
**Why each option:**
**A.** Inhibition of platelet aggregation describes aspirin's mechanism; aspirin is also used in essential thrombocythemia but is not the SCD-linked drug being asked about.
**B.** Correct. Hydroxyurea induces fetal hemoglobin (HbF) production in sickle cell disease, diluting HbS and preventing polymerization; in ET it acts as a cytoreductive ribonucleotide reductase inhibitor.
**C.** Hydroxyurea inhibits DNA synthesis (ribonucleotide reductase) but does not block stem cell differentiation; the SCD benefit is HbF induction, not differentiation arrest.
**D.** Restoration of iron stores is the mechanism of iron supplementation in iron deficiency anemia, unrelated to hydroxyurea or sickle cell disease.