Family Medicine Board Review · Case-Based · Difficult Level

Sickle Cell Disease — Clinical Vignette MCQs

Board-style cases built from the SCD summary — complication recognition, transfusion decision rules, vaccination logistics, lab interpretation, and hydroxyurea safety. Tap "Reveal Answer" on each, then read the pearl.

10 Questions ●●●● Difficult Single Best Answer

Q1Stroke — Age-Based Type●●●●● Extreme

A 6-year-old boy with known HbSS disease presents with new-onset right-sided weakness and slurred speech. His grandmother, also with HbSS disease, had a similar presentation at age 68. A 24-year-old man with HbSS disease in the same family presented with a severe headache and altered mental status last year. Which stroke subtype is each patient most likely to have experienced?

A. All three are equally likely to have hemorrhagic stroke
B. The 6-year-old and grandmother: ischemic stroke; the 24-year-old: hemorrhagic stroke
C. The 6-year-old and grandmother: hemorrhagic stroke; the 24-year-old: ischemic stroke
D. Age has no bearing on stroke subtype in SCD
E. All three are most likely to have ischemic stroke regardless of age

Reveal Answer

Correct answer: B

In SCD, children and older adults are more prone to ischemic stroke, while young adults are more prone to hemorrhagic stroke. This age-based split matches the 6-year-old and grandmother (ischemic) versus the 24-year-old (hemorrhagic).

Why the others are wrong A/D/E — all ignore the well-established age-dependent pattern specific to SCD stroke epidemiology, which does not mirror general population stroke risk patterns. C — reverses the correct age associations.

Exam Pearl SCD stroke pattern: children + elderly → ischemic; young adults → hemorrhagic. All stroke subtypes in SCD require exchange transfusion plus routine stroke management regardless of type.

Q2Transfusion Decision Rule●●●●● Extreme

A 22-year-old woman with HbSS disease presents with acute chest syndrome. Vital signs show tachycardia and hypotension (unstable). Hemoglobin is 6.2 g/dL. What is the most appropriate initial transfusion strategy?

A. Immediate exchange transfusion, bypassing simple transfusion entirely
B. Simple transfusion first, since she is hemodynamically unstable and Hb is below 7 g/dL; consider exchange transfusion afterward if still needed
C. No transfusion indicated since Hb is above 5 g/dL
D. Withhold transfusion until HPLC results confirm the diagnosis
E. Exchange transfusion only if Hb rises above 9 g/dL first

Reveal Answer

Correct answer: B

The decision rule: if vital signs are unstable and Hb is below 7 g/dL, go for simple transfusion first, then proceed to exchange transfusion afterward if still clinically indicated (e.g., for severe/refractory acute chest syndrome).

Why the others are wrong A — bypassing simple transfusion isn't the rule when Hb is this low and the patient is unstable; simple transfusion is appropriate first-line here. C — she has acute chest syndrome with hemodynamic instability, which is a transfusion indication regardless of the exact Hb cutoff debate; withholding transfusion is inappropriate. D — she has an established SCD diagnosis (implied); an acute life-threatening complication shouldn't wait for confirmatory testing before treatment. E — this misapplies the "Hb ≥9 → always exchange" rule, which doesn't apply to her current Hb of 6.2.

Exam Pearl Memorize both ends of the transfusion rule: unstable + Hb <7 → simple transfusion (± exchange after); Hb ≥9 → always exchange transfusion (never simple, to avoid hyperviscosity from adding volume on top of an already higher Hb).

Q3Transfusion Decision Rule — Flip Side●●●●● Extreme

A 19-year-old man with HbSS disease requires transfusion support prior to a major elective surgery. His hemoglobin is 9.4 g/dL and he is hemodynamically stable. What is the most appropriate transfusion approach?

A. Simple transfusion, since his hemoglobin is relatively preserved
B. Exchange transfusion, since his Hb is 9 g/dL or above
C. No transfusion is needed since he is stable
D. Simple transfusion only if his Hb drops below 7 g/dL intraoperatively
E. Defer any transfusion decision until after surgery

Reveal Answer

Correct answer: B

When Hb is 9 g/dL or above, the rule is to always go for exchange transfusion — simple transfusion in this setting risks excessive viscosity and its complications. Preparation for major surgery is also a specifically listed indication for exchange transfusion.

Why the others are wrong A — simple transfusion is specifically avoided when Hb is already ≥9 g/dL. C — preoperative transfusion support is a recognized indication in SCD patients undergoing major surgery, regardless of baseline stability. D — this misapplies the low-Hb/unstable rule to a patient who doesn't meet those criteria. E — deferring transfusion planning until after major surgery ignores the preoperative indication for exchange transfusion.

Exam Pearl The "Hb ≥9 → always exchange" rule applies regardless of hemodynamic stability — it's purely Hb-driven, unlike the low-Hb rule which is tied to instability. Preparation for major surgery is a specific listed indication for exchange transfusion.

Q4Vaccination Logistics●●●● Very Hard

A 9-year-old girl with HbSS disease requires an emergency splenectomy for uncontrolled splenic sequestration. She has not previously received pneumococcal, meningococcal, or Hib vaccination. What is the most appropriate vaccination plan?

A. Administer all indicated vaccines at least 2 weeks before surgery
B. Administer the indicated vaccines (S. pneumoniae, N. meningitidis, H. influenzae type b, influenza) at least 2 weeks after the surgical intervention, since this is an emergency case
C. No vaccination is needed since she is already on penicillin prophylaxis
D. Delay all vaccination indefinitely until she turns 18
E. Give live vaccines only, avoiding inactivated vaccines postoperatively

Reveal Answer

Correct answer: B

Vaccination timing differs by surgical urgency: elective splenectomy → vaccinate at least 2 weeks before surgery; emergency splenectomy → vaccinate at least 2 weeks after the surgical intervention. Since this is an emergency case, vaccines should be given post-operatively at the appropriate interval.

Why the others are wrong A — this is the correct approach for elective splenectomy, but this patient's surgery is emergent, so the timing rule flips to post-operative. C — penicillin prophylaxis addresses only a portion of infection risk (and only certain organisms); it doesn't replace the need for vaccination against encapsulated organisms. D — indefinite delay leaves her at prolonged high risk for overwhelming post-splenectomy infection. E — this doesn't reflect the actual recommendation, which is about timing relative to surgery, not vaccine type restriction.

Exam Pearl Splenectomy vaccine timing: elective → 2 weeks before; emergency → 2 weeks after. Vaccines needed: S. pneumoniae, N. meningitidis, H. influenzae type b, and influenza.

Q5Lab Interpretation●●●●● Extreme

A 26-year-old asymptomatic man undergoes hemoglobin electrophoresis as part of a premarital screening panel. His sickle solubility test is positive. HPLC shows HbS of 38%. What is the most accurate interpretation of these findings?

A. He has sickle cell disease, since the solubility test is positive
B. He has sickle cell trait (HbAS), consistent with HbS 45% or less on HPLC; the solubility test alone could not have distinguished trait from disease
C. The results are inconclusive and require repeat solubility testing only
D. He has sickle cell beta-thalassemia based on these findings
E. These findings indicate a laboratory error, since solubility testing and HPLC should never both be performed

Reveal Answer

Correct answer: B

The sickle solubility test detects the presence of HbS but cannot distinguish trait from disease — a positive result alone is not diagnostic of disease severity. HPLC is required for quantification: HbS 45% or less is consistent with sickle cell trait, while HbS 65% or above indicates sickle cell disease. His HbS of 38% places him in the trait category.

Why the others are wrong A — incorrectly treats the qualitative solubility test as diagnostic of disease severity, which it cannot determine. C — the results are not inconclusive; HPLC has already provided the definitive quantitative answer. D — sickle cell beta-thalassemia would be suggested by an elevated HbA2 (≥5.5%), not simply by this HbS percentage; no HbA2 value is given to support this. E — this pairing of tests (solubility screening + HPLC confirmation/quantification) is a standard, appropriate diagnostic workflow, not an error.

Exam Pearl Solubility test = screening only (can't distinguish trait vs. disease). HPLC cutoffs: trait ≤45% HbS, disease ≥65% HbS. Elevated HbA2 (≥5.5%) should raise concern for concurrent sickle cell beta-thalassemia.

Q6Acute Complication Recognition●●●● Very Hard

A 5-year-old girl with HbSS disease is brought in by her mother for lethargy and pallor. She had a mild upper respiratory illness with low-grade fever 10 days ago that resolved without treatment. Exam shows pallor without significant splenomegaly. Hemoglobin is 4.8 g/dL (baseline 8.5 g/dL), with a low reticulocyte count. What is the most likely underlying cause?

A. Splenic sequestration crisis
B. Aplastic crisis due to parvovirus B19 infection
C. Acute chest syndrome
D. Hemolytic transfusion reaction
E. Vaso-occlusive painful crisis

Reveal Answer

Correct answer: B

A preceding viral illness, significant Hb drop, and — critically — a low reticulocyte count (rather than the expected reticulocytosis of ongoing hemolysis) point to aplastic crisis, classically caused by parvovirus B19 (also EBV). This reflects transient bone marrow suppression of erythropoiesis rather than increased destruction or sequestration.

Why the others are wrong A — splenic sequestration presents with LUQ pain and a palpable, enlarging spleen; this patient has no significant splenomegaly noted, and sequestration would typically show an appropriately elevated (compensatory) reticulocyte response, not a low one. C — acute chest syndrome presents with chest pain, cough, dyspnea, fever, and a CXR infiltrate — not described here. D — no transfusion history is provided to support a hemolytic transfusion reaction. E — vaso-occlusive crisis presents primarily with pain, not this isolated pattern of anemia with reticulocytopenia following a viral illness.

Exam Pearl The reticulocyte count is the key discriminator: aplastic crisis (viral, especially parvovirus B19) causes a Hb drop with a low/inappropriately normal reticulocyte count, while sequestration and hemolysis typically show a robust reticulocyte response.

Q7Hydroxyurea Safety●●●●● Extreme

A 29-year-old woman with HbSS disease on chronic hydroxyurea therapy and her 31-year-old male partner (unaffected) are planning to conceive in 2 months. She is also currently breastfeeding her 8-month-old from a previous pregnancy and had planned to continue. What is the most appropriate guidance regarding hydroxyurea?

A. Continue hydroxyurea during breastfeeding and conception attempts without any changes
B. She should stop hydroxyurea at least 3 months before conception, her partner should also stop his hydroxyurea (if applicable) 3 months prior, and hydroxyurea is not recommended during breastfeeding
C. Only the female partner needs to stop hydroxyurea; the male partner's use has no bearing on conception timing
D. Hydroxyurea only needs to be stopped once pregnancy is confirmed, not beforehand
E. Hydroxyurea is safe during breastfeeding but must be stopped 6 months before conception

Reveal Answer

Correct answer: B

Hydroxyurea should be stopped 3 months before planning pregnancy for both males and females given its reported teratogenic potential, and it is not recommended during breastfeeding. Given she is trying to conceive in 2 months, this timeline needs adjustment (stopping now, or delaying conception) to meet the 3-month washout period, and breastfeeding plans should also be reconsidered if she remains on therapy.

Why the others are wrong A — contradicts both the pregnancy-planning stop rule and the breastfeeding recommendation. C — the stop rule explicitly applies to both male and female partners when hydroxyurea is in use, not just the female. D — stopping only after conception is confirmed misses the critical periconceptional and early embryonic window; the 3-month pre-conception washout is specifically recommended. E — the timeline is 3 months, not 6, and breastfeeding is not considered safe on hydroxyurea per this guidance.

Exam Pearl Hydroxyurea + reproduction: stop 3 months before conception — applies to both partners — and avoid during breastfeeding. This is a classic isolated safety fact tested in reproductive-age SCD patients.

Q8Screening Calendar●●●● Very Hard

A 10-year-old boy with HbSS disease is due for his annual well visit. His mother asks which age-specific screening tests he should be receiving. Which pairing is correct?

A. Transcranial Doppler (indicated, age 2–16) and retinal exam (indicated, started at age 8)
B. Transcranial Doppler only; retinal exams don't start until age 18
C. Echocardiography annually starting at birth
D. DXA scan annually per established guidelines
E. Neither transcranial Doppler nor retinal exam is indicated until adulthood

Reveal Answer

Correct answer: A

At age 10, this patient falls within the recommended windows for both: transcranial Doppler annually from age 2–16 (stroke risk prevention) and retinal examinations annually starting at age 8 (retinopathy screening).

Why the others are wrong B — retinal exams start at age 8, well before age 18; this patient should already be receiving them. C — echocardiography is done once in late childhood/early adulthood, not annually, and not starting at birth. D — there is no clear indication for DXA scan timing per this guidance; it's not an established annual test. E — both screening tests are already indicated at age 10.

Exam Pearl Know the distinct windows: TCD = annual, ages 2–16; retinal exam = annual, starting age 8 (no stated upper limit); echocardiography = once, not annual, in late childhood/early adulthood. Don't collapse these into one generic "annual screening" answer.

Q9SCD + Diabetes Monitoring●●●● Very Hard

A 45-year-old woman with HbSS disease and type 2 diabetes is being followed for glycemic control. Her hemoglobin A1c results have been inconsistent with her home glucose log and seem falsely low given her reported readings. What is the most appropriate explanation and next step?

A. HbA1c is unreliable in SCD due to altered red cell turnover; fructosamine should be used instead to monitor glycemic control
B. Her glucose meter is malfunctioning; replace the device
C. HbA1c remains the gold standard in SCD and should be trusted over her glucose log
D. Order a random cortisol level to explain the discrepancy
E. Increase testing frequency of HbA1c to twice monthly to improve accuracy

Reveal Answer

Correct answer: A

In SCD, chronic hemolysis and altered red blood cell turnover make HbA1c unreliable (often falsely low, since RBCs don't survive long enough to accumulate glycation to the same degree as normal-lifespan cells). Fructosamine, which reflects glycemic control over a shorter recent window and is unaffected by hemoglobinopathies, should be used instead.

Why the others are wrong B — there's no specific indication her glucose meter is malfunctioning; the more likely explanation is the known HbA1c unreliability in SCD. C — this is the opposite of the correct teaching; HbA1c is specifically unreliable in this population. D — there's no clinical indication pointing to a cortisol-related explanation for this discrepancy. E — increasing frequency doesn't fix the fundamental issue of altered RBC lifespan affecting the test's validity.

Exam Pearl SCD + diabetes → use fructosamine, not HbA1c, to monitor glycemic control, since hemoglobinopathies and altered RBC turnover distort HbA1c accuracy.

Q10Integrative — Supplements & Deficiency●●●● Very Hard

A 14-year-old boy with HbSS disease on a stable regimen presents with poor wound healing, hair thinning, and decreased appetite. Basic labs are otherwise unremarkable. Which nutrient deficiency should specifically be considered in this population, and what is the standard baseline supplementation approach for SCD patients in general?

A. Iron deficiency; all SCD patients should receive routine iron supplementation
B. Zinc deficiency, given SCD patients are more prone to it; baseline supplements for all SCD patients include folic acid and a multivitamin without iron
C. Vitamin B12 deficiency; all SCD patients require monthly B12 injections
D. Copper deficiency; no baseline supplementation is recommended for any SCD patient
E. Selenium deficiency; iron supplementation should be maximized in all SCD patients

Reveal Answer

Correct answer: B

SCD patients are specifically more prone to zinc deficiency, and this presentation (poor wound healing, hair thinning, decreased appetite) is classic for it — zinc should be replaced if deficient. Standard baseline supplementation for all SCD patients includes folic acid and a multivitamin without iron, with vitamin D/calcium and zinc added only if deficiency is confirmed.

Why the others are wrong A — routine iron supplementation is specifically avoided in SCD (multivitamin is given without iron) due to iron overload risk from chronic hemolysis/transfusions. C — there's no described basis for B12 deficiency in this case, and routine monthly B12 injections aren't part of standard SCD supplementation. D — copper deficiency isn't the specifically flagged nutrient issue in SCD; zinc is. E — selenium isn't the tested nutrient here, and maximizing iron is directly contraindicated as a default approach.

Exam Pearl Baseline SCD supplements: folic acid for all + multivitamin without iron for all; add vitamin D/calcium if deficient, and specifically consider zinc replacement given the population's increased susceptibility to zinc deficiency (poor wound healing, hair loss, taste changes, growth impairment are classic zinc-deficiency clues).