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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
Key points
- Sickle cell disease causes chronic hemolytic anemia and episodic vaso-occlusion from HbS polymerization
- Vaso-occlusive pain crisis is treated with rapid analgesia, hydration only when dehydrated, and evaluation for triggers
- Acute chest syndrome = new pulmonary infiltrate plus chest pain, fever, cough, tachypnea, or hypoxemia
- Hydroxyurea increases HbF and reduces pain crises and acute chest syndrome
- Functional asplenia increases risk of encapsulated organisms; fever is an emergency
Overview
Sickle cell disease is an autosomal recessive hemoglobinopathy caused by a beta-globin mutation producing hemoglobin S. Deoxygenation promotes HbS polymerization, RBC sickling, hemolysis, endothelial injury, and microvascular occlusion. The disease produces both chronic anemia and acute complications: pain crises, acute chest syndrome, stroke, splenic sequestration, aplastic crisis, priapism, infection, and avascular necrosis.
Epidemiology
Sickle cell disease affects approximately 100,000 people in the United States and is most common among people of African ancestry, though it also occurs in Mediterranean, Middle Eastern, Indian, Caribbean, and Latin American populations. Newborn screening is universal in the United States.
Clinical Features
Symptoms
Severe episodic pain in back, chest, abdomen, or extremities from vaso-occlusion
Fever or infectious symptoms — medical emergency because of functional asplenia
Chest pain, cough, dyspnea, or hypoxemia suggesting acute chest syndrome
Neurologic deficit or severe headache suggesting stroke
Priapism, abdominal pain, or left upper quadrant fullness
Signs
Pallor, jaundice, scleral icterus from hemolysis
Tachycardia, dehydration, pain distress
New crackles, fever, low oxygen saturation in acute chest syndrome
Splenomegaly with shock in splenic sequestration, especially children
Functional asplenia: Howell-Jolly bodies on smear
Investigations
First-line
CBC with reticulocyte countChronic anemia with elevated reticulocytes; retic drop suggests aplastic crisis
Peripheral smearSickled cells, target cells, Howell-Jolly bodies after functional asplenia
Pulse oximetry and chest X-ray when respiratory symptomsAcute chest syndrome requires new infiltrate plus compatible symptoms
Second-line
Hemoglobin electrophoresis or HPLCConfirms genotype: HbSS has predominant HbS, no HbA, variable HbF
Type and screenNeeded when severe anemia, acute chest syndrome, stroke, or transfusion likely
Blood cultures and infection workup if febrileFever requires prompt empiric antibiotics because sepsis risk is high
Specialist
Transcranial Doppler in childrenScreens for stroke risk; abnormal velocities prompt chronic transfusion
MRI/MRA brainEvaluate stroke, silent infarcts, or neurologic symptoms
Pulmonary hypertension and renal screeningEcho, urine albumin, and renal function assessment in chronic care
1
Vaso-occlusive pain crisis
- Assess pain promptly and give rapid opioid analgesia when severe
- Use IV fluids only for dehydration; avoid overhydration because it can worsen pulmonary complications
- Give oxygen only for hypoxemia, not routinely for normal saturation
- Evaluate for acute chest syndrome, infection, splenic sequestration, and aplastic crisis
2
Acute chest syndrome
- Treat with oxygen, incentive spirometry, bronchodilator if wheezing, ceftriaxone plus azithromycin, and analgesia
- Simple or exchange transfusion for severe hypoxemia, multilobar disease, rapid progression, or falling hemoglobin
3
Disease modification and prevention
- Hydroxyurea for recurrent pain crises, acute chest syndrome, severe anemia, or many adults with HbSS
- Vaccinations: pneumococcal, meningococcal, Hib, influenza, COVID; childhood penicillin prophylaxis
- Curative options include hematopoietic stem cell transplant in selected patients; gene therapies are emerging specialist options
4
Transfusion indications
- Acute stroke or high-risk TCD: urgent exchange transfusion/chronic transfusion program
- Severe symptomatic anemia, splenic sequestration, aplastic crisis, severe acute chest syndrome
- Avoid unnecessary transfusion for uncomplicated pain crisis
Complications
- Acute chest syndrome: Leading cause of ICU admission and death
- Stroke: Ischemic stroke in children; hemorrhagic and ischemic events in adults
- Functional asplenia: Sepsis from encapsulated organisms
- Aplastic crisis: Parvovirus B19 causes reticulocytopenia and abrupt Hb drop
- Chronic organ damage: CKD, pulmonary hypertension, leg ulcers, avascular necrosis, retinopathy
USMLE Step 2 CK Exam Tips
- 1Pain crisis: analgesia first; do not undertreat pain while waiting for labs
- 2Acute chest syndrome: new infiltrate plus respiratory symptoms; treat with antibiotics and consider transfusion
- 3Parvovirus B19 aplastic crisis: sudden anemia with low reticulocyte count
- 4Sequestration crisis: severe anemia with splenomegaly and shock in a child
- 5Functional asplenia causes Howell-Jolly bodies and risk from encapsulated organisms
- 6Hydroxyurea increases fetal hemoglobin and reduces crises
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