Sickle Cell Disease -- Smith

A 2-year-old boy presents with dactylitis, fatigue, and recurrent infections. His newborn screen was positive for HbS. Which laboratory finding is MOST consistent with sickle cell disease?

A. Elevated HbA

B. Elevated HbF

C. Elevated HbS

D. Low reticulocyte count

C. Elevated HbS

Rationale: SCD is caused by abnormal HbS. HbA is reduced/absent in SCD. HbF may persist in infants and can lessen symptoms, but it is not the primary abnormality. Reticulocyte count is typically elevated (not low) due to compensatory marrow activity.

Which of the following is a hallmark of pathophysiologic feature of sickle cell disease?

A. Increased red blood cell lifespan

B. Decreased risk of infection due to splenic hypertrophy

C. Abnormal hemoglobin polymerization under deoxygenated states

D. Reduced reticulocyte production

C. Abnormal hemoglobin polymerization under deoxygenated states

Rationale: HbS polymerizes when deoxygenated, distorting RBC shape and causing vaso-occlusion. RBC lifespan is shortened (10-20 days). Splenic infarction causes asplenia (↑ infection risk). Reticulocyte count is elevated.

A 7-month-old infant with HbSS presents with pallor, irritability, and a hemoglobin of 7.8 g/dL. Which is the MOST likely explanation for symptom onset at this age?

A. HbA levels rise significantly after birth

B. HbF levels decrease, unmasking HbS-related complications

C. Iron deficiency typically begins at 6 months

D. Transfusion reactions typically occur after infancy

B. HbF levels decrease, unmasking HbS-related complications

Rationale: HbF protects against sickling. As HbF declines at ~4-6 months, HbS becomes predominant, leading to anemia and clinical manifestations.

Which of the following complications is MOST directly associated with functional asplenia in sickle cell disease?

A. Vaso-occlusive crises

B. Increased risk of infection from encapsulated bacteria

C. Iron overload

D. Stroke

B. Increased risk of infection from encapsulated bacteria

Rationale: Repeated splenic infarctions cause functional asplenia, leaving patients susceptible to encapsulated bacteria (S. pneumoniae, H. influenzae, N. meningitidis). VOCs and stroke are complications of vaso-occlusion, not directly linked to asplenia. Iron overload is related to transfusion therapy.

Which of the following is the MOST serious adverse effect of hydroxyurea requiring regular monitoring?

A. Constipation

B. Bone marrow suppression

C. Hyperpigmentation of nails

D. Headache

B. Bone marrow suppression

Rationale: Hydroxyurea can cause neutropenia and thrombocytopenia, requiring CBC monitoring. Hyperpigmentation, rash, and GI upset may occur but are not dose-limiting.

A patient with SCD receiving deferasirox (Exjade) for iron overload develops ringing in the ears and blurry vision. Which recommendation is MOST appropriate?

A. Continue therapy; these are mild expected effects

B. Stop therapy and evaluate for serious toxicity

C. Switch to hydroxyurea

D. Add aluminum hydroxide to reduce GI upset

B. Stop therapy and evaluate for serious toxicity

Rationale: Deferasirox can cause visual and auditory changes, which may be irreversible. Therapy should be stopped and the patient evaluated. Hydroxyurea is not an alternative for chelation. Antacids should be avoided due to drug interactions.

Which of the following side effects is MOST commonly associated with L-glutamine (Endari)?

A. Bone marrow suppression

B. Constipation and abdominal pain

C. Nephrotoxicity

D. Rash with ulceration

B. Constipation and abdominal pain

Rationale: L-glutamine is generally well tolerated. Common adverse effects include GI upset, headache, and chest pain. It does not cause bone marrow suppression (hydroxyurea), nephrotoxicity (deferasirox risk), or severe rashes.

Crizanlizumab is associated with which of the following infusion-related adverse effects?

A. Pruritus and urticaria

B. Severe constipation

C. Hepatotoxicity

D. Macrocytosis

A. Pruritus and urticaria

Rationale: Crizanlizumab is an IV infusion that may cause infusion-related reactions (pruritus, rash, urticaria, fever, chills). Macrocytosis is seen with hydroxyurea. Constipation = L-glutamine. Hepatotoxicity = iron chelators.

A 2-year-old child with sickle cell disease is prescribed prophylactic penicillin. What is the correct dose and duration?

A. Penicillin VK 125 mg PO BID until age 2

B. Penicillin VK 125 mg PO BID until age 5

C. Penicillin VK 250 mg PO BID until age 5

D. Penicillin VK 250 mg PO BID until age 10

C. Penicillin VK 250 mg PO BID until age 5

Rationale: Prophylactic penicillin prevents pneumococcal infection in children with functional asplenia. Dosing: 125 mg BID (age 2 mo-3 yrs), 250 mg BID (3-5 yrs). Discontinued after age 5 if no splenectomy or invasive infection history.

Which vaccines are most critical for patients with functional asplenia due to sickle cell disease?

A. Hepatitis B and HPV

B. Pneumococcal, meningococcal, Haemophilus influenzae type b

C. Influenza and varicella

D. Tdap and MMR

B. Pneumococcal, meningococcal, Haemophilus influenzae type b

Rationale: Patients with SCD have ↑ risk of infection from encapsulated bacteria due to asplenia. These vaccines are essential. All routine vaccines (influenza, MMR, etc.) should also be given, but encapsulated coverage is priority.

Which of the following is an inappropriate indication for blood transfusion therapy in SCD?

A. Acute stroke prevention

B. Acute chest syndrome with hypoxemia

C. Simple painful vaso-occlusive crisis

D. Symptomatic severe anemia

C. Simple painful vaso-occlusive crisis

Rationale: Transfusions are NOT recommended for uncomplicated VOCs. Appropriate indications include stroke prevention, ACS, severe anemia with symptoms. Risks of transfusion include iron overload, alloimmunization, and infections.

A patient with SCD has ferritin >1,500 mcg/L after multiple transfusions. Which therapy is most appropriate?

A. Hydroxyurea

B. Deferasirox (Exjade)

C. L-glutamine (Endari)

D. Crizanlizumab (Adakveo)

B. Deferasirox (Exjade)

Rationale: Chelation therapy is used for iron overload from chronic transfusions. Agents: deferasirox, deferiprone, deferoxamine. Hydroxyurea and others modify disease but do not treat iron overload.

A 13-year-old with HbSS has 3 VOCs/year and no prior disease-modifying therapy. Vaccines are up-to-date; no contraindications noted. Best next step?

A. Start L-glutamine

B. Start hydroxyurea

C. Begin chronic transfusions

D. Start crizanlizumab

B. Start hydroxyurea

Rationale: Hydroxyurea is first-line disease-modifying therapy in patients ≥2 years with recurrent VOCs. L-glutamine/crizanlizumab are options if HU is inadequate or not tolerated. Chronic transfusions are reserved for select indications (e.g., stroke prevention).

A 24-year-old with HbSS has frequent VOCs despite adherent hydroxyurea. She asks about add-on therapy to reduce crises. Best option?

A. Add crizanlizumab

B. Add deferasirox

C. Add penicillin VK

D. Start voxelotor for iron overload

A. Add crizanlizumab

Crizanlizumab (IV) reduces frequency of VOCs. Deferasirox treats iron overload, not VOCs. Penicillin VK is pediatric prophylaxis for pneumococcus. Voxelotor (if considered) targets hemolysis/hemoglobin, not iron overload.

A 30-year-old hospitalized with ACS (new infiltrate, hypoxemia) asks about treatment. Which plan is most appropriate?

A. IV fluids, opioids only

B. Ceftriaxone + azithromycin, oxygen, incentive spirometry; consider transfusion if Hgb

B. Ceftriaxone + azithromycin, oxygen, incentive spirometry; consider transfusion if Hgb

A 4-year-old with HbSS presents for routine care. Which of the following should be included now in the therapeutic plan?

A. Discontinue all vaccines after age 4

B. Continue penicillin VK 250 mg PO BID through age 5 (if no splenectomy/invasive infection history)

C. Start chelation for ferritin 200 ng/mL

D. Begin long-term oxygen at home

B. Continue penicillin VK 250 mg PO BID through age 5 (if no splenectomy/invasive infection history)

Penicillin prophylaxis age-appropriate dosing continues through age 5 in many patients. Vaccines continue per schedule; ferritin 200 ng/mL doesn't warrant chelation; home O2 without indication isn't standard.

Which lab best correlates with hydroxyurea adherence/response?

A. MCV

B. ESR

C. INR

D. CK

A. MCV

Rationale: MCV rises with HU (macrocytosis) and helps gauge adherence; efficacy also seen with fewer VOCs and ↑HbF.

A patient on deferasirox for transfusional iron overload needs which routine monitoring?

A. Audiology and ophthalmology only

B. CBC only

C. Renal and hepatic function; consider ophthalmic/audiology if symptomatic

D. No routine monitoring

C. Renal and hepatic function; consider ophthalmic/audiology if symptomatic

Rationale: Deferasirox can cause renal/hepatic toxicity; periodic labs are required. Visual/auditory changes warrant prompt evaluation.

HU causes ANC 800/µL and platelets 70K/µL. Best action?

A. Continue current dose; recheck in 3 months

B. Stop HU 1-2 weeks; when counts recover, resume 5 mg/day lower than prior dose

C. Permanently discontinue HU

D. Add G-CSF and continue HU

B. Stop HU 1-2 weeks; when counts recover, resume 5 mg/day lower than prior dose

Rationale: For HU-induced cytopenias, hold 1-2 weeks, then resume at a slightly lower dose once counts normalize.

A patient on chronic transfusions presents 10 days post-transfusion with dark urine and falling Hgb. Priority assessment?A. Check TSH

B. Evaluate for delayed hemolytic transfusion reaction

C. Start iron chelation immediately

D. Ignore—this is expected

B. Evaluate for delayed hemolytic transfusion reaction

Rationale: Delayed hemolytic transfusion reactions can occur ~2-20 days post-transfusion and may be life-threatening; urgent evaluation is needed.

Which counseling point for hydroxyurea is correct?

A. Double the next dose if a dose is missed

B. Contraception is recommended during therapy

C. Expect immediate clinical response within 1 week

D. Stop therapy after 4 weeks if no change

B. Contraception is recommended during therapy

Rationale: HU is teratogenic—use contraception. Missed doses should not be doubled. Clinical response may take 3-6 months; minimum trial ~6 months before declaring failure.

Key counseling for L-glutamine (Endari) includes:

A. Take with hot tea to dissolve

B. Use only the Endari brand/formulation; mix packets with 8 oz cool/room-temp beverage or food

C. Take with aluminum antacids

D. Skip doses if feeling well

B. Use only the Endari brand/formulation; mix packets with 8 oz cool/room-temp beverage or food

Rationale: Use the specific brand/formulation; mix properly. Avoid aluminum antacids with certain chelators (not L-glutamine).

Which statement is appropriate for chelation therapy counseling?

A. "Your urine may appear pink-orange while on therapy."

B. "No eye/hearing issues can occur."

C. "You don't need labs."

D. "Always take with a heavy meal to reduce efficacy."

A. "Your urine may appear pink-orange while on therapy."

Rationale: Some iron chelators can discolor urine pink-to-orange. Patients should report visual/hearing changes and obtain routine labs.

A teen with HbSS starting opioids for VOC asks about side effects. Best counseling?

A. Avoid bowel regimen to prevent diarrhea

B. Use a bowel regimen to prevent constipation

C. Opioids cure VOC

D. Stop all nonopioids

B. Use a bowel regimen to prevent constipation

Rationale: Opioids are often necessary for VOC pain, but constipation prophylaxis (stool softener ± stimulant) is standard. Nonopioids and non-pharm measures remain important.

Which non-pharmacologic strategy helps prevent VOCs?

A. Dehydration to concentrate blood

B. Avoiding extreme temperatures; maintain hydration and use heat packs for pain

C. High-intensity exercise during crises

D. Routine bed rest for months

B. Avoiding extreme temperatures; maintain hydration and use heat packs for pain

Rationale: Hydration, avoiding extremes of temperature, and local heat can reduce VOC frequency/severity.

A 17-year-old with recurrent VOCs despite HU wants another option to reduce crisis frequency. Which agent fits?

A. Deferiprone

B. Crizanlizumab

C. Ferrous sulfate

D. Azithromycin

B. Crizanlizumab

Rationale: Crizanlizumab reduces VOCs. Deferiprone is a chelator; iron and azithro don't prevent VOCs.

A child with HbSS is 3 months old and had a positive newborn screen. Next step to mitigate infection risk?

A. Start penicillin VK prophylaxis

B. Start crizanlizumab

C. Begin chelation

D. No action until age 2

A. Start penicillin VK prophylaxis

Rationale: Newborn screening followed by early penicillin prophylaxis helps prevent invasive pneumococcal disease.

A 9-year-old with abnormal transcranial Doppler velocities is at high risk of stroke. Best preventive approach?

A. Start L-glutamine

B. Initiate chronic transfusion program

C. Start crizanlizumab

D. Begin voxelotor for iron overload

B. Initiate chronic transfusion program

Rationale: Chronic transfusions are used for stroke prevention in high-risk children. L-glutamine/crizanlizumab target VOCs; voxelotor addresses hemolysis, not iron overload.

A 6-month-old with HbSS has fever (38.9°C), irritability, and WBC 22K. Most likely complication needing urgent evaluation?A. Simple VOC

B. Functional asplenia with invasive infection risk

C. Iron overload

D. Priapism

B. Functional asplenia with invasive infection risk

Rationale: Infants with HbSS are at high risk of severe infection due to functional asplenia—requires prompt evaluation and empiric antibiotics.

A 22-year-old with HbSS has acute chest pain, cough, fever, O₂ sat 88%, and new infiltrate on CXR. Diagnosis?

A. Community-acquired pneumonia only

B. Acute chest syndrome

C. Uncomplicated VOC

D. Pulmonary embolism ruled in

B. Acute chest syndrome

ACS = new infiltrate plus respiratory symptoms/signs (fever, hypoxemia, chest pain, cough, wheeze).

A 9-year-old with HbSS has swollen painful hands/feet and elevated reticulocytes. Most likely diagnosis?

A. Dactylitis

B. Osteomyelitis

C. Septic arthritis

D. Splenic sequestration

A. Dactylitis

Rationale: Dactylitis (hand-foot syndrome) is common in young children with SCD and presents with painful swelling of hands/feet.

A 25-year-old with HbSS, Hgb 7.5 g/dL, dark urine, and jaundice 10 days after transfusion. Most likely?

A. Vitamin B12 deficiency

B. Delayed hemolytic transfusion reaction

C. Uncomplicated VOC

D. ACS

B. Delayed hemolytic transfusion reaction

Rationale: Timing (7-10 days), falling Hgb, and hemolysis signs point to delayed hemolytic transfusion reaction.