WBR0327

{{WBRQuestion |QuestionAuthor=Rim Halaby, M.D. [1] (Reviewed by Alison Leibowitz) |ExamType=USMLE Step 1 |MainCategory=Pharmacology |SubCategory=Hematology |MainCategory=Pharmacology |SubCategory=Hematology |MainCategory=Pharmacology |SubCategory=Hematology |MainCategory=Pharmacology |MainCategory=Pharmacology |SubCategory=Hematology |MainCategory=Pharmacology |SubCategory=Hematology |MainCategory=Pharmacology |SubCategory=Hematology |MainCategory=Pharmacology |SubCategory=Hematology |MainCategory=Pharmacology |MainCategory=Pharmacology |SubCategory=Hematology |Prompt=Brought by his parents, a 3-year-old African American male presents to the ER with irritability and swelling in the hands and feet. A peripheral smear (illustrated below) demonstrates findings consistent with the patient's condition. To relieve his symptoms, the patient is started on a chemotherapeutic agent. By which of the following mechanisms does the prescribed medication help relieve the patient's symptoms?

|Explanation=The patient in this scenario is most likely diagnosed with sickle cell disease. A peripheral smear demonstrates sickle-looking red blood cells, consistent with the diagnosis. Patients with sickle cell disease often require hydroxyurea, which provides symptomatic relief by increasing HbF levels. HbF has high affinity for oxygen and may aid in the delivery of oxygen to peripheral tissues in patients with SCD. Hydroxyurea is a chemotherapeutic agent that hinders ribonucleotide reductase ability to decrease DNA synthesis during S-phase. It is typically used to treat cancers, such as melanoma and CML. Common side effects of hydroxyurea include GI symptoms, bone marrow suppression, and an increased risk of developing leukemias.

|EducationalObjectives= Hydroxyurea often administered to patients with sickle cell disease in order to increase HbF levels.

|AnswerA=Increase in HbF levels |AnswerAExp=Hydroxyurea is beneficial in patients with sickle cell disease (SCD) because it increases HbF levels. |AnswerB=Decrease in thymidylate synthase activity |AnswerBExp=5-Fluorouracil is known to inhibit thymidylate synthase. |AnswerC=Increase in ribonucleotide reductase activity |AnswerCExp=Hydroxyurea inhibits ribonucleotide reductase, which is not beneficial to patients with SCD. |AnswerD=Increase in HbA levels |AnswerDExp=Patients with SCD have low HbA levels, but hydroxyurea is beneficial in patients with sickle cell disease (SCD) because it increases HbF levels. |AnswerE=Systemic vasodilatory effect |AnswerEExp=Vasodilation is helpful for patients with SCD, but is not the mechanism by which hydroxyurea is beneficial. |RightAnswer=A |WBRKeyword=HbF, hemoglobin, hemoglobinopathy, hemoglinopathies, sickle cell disease, peripheral, HbC, HbS, hydroxyurea, |Approved=Yes