Hematology · Sickle Cell Disease
The facts most likely to be tested
Vaso-occlusive crisis is triggered by hypoxia, dehydration, acidosis, or infection, leading to sickling of erythrocytes and microvascular obstruction.
Dactylitis (hand-foot syndrome) is the most common initial presentation in infants due to infarction of the metacarpals and metatarsals.
Acute Chest Syndrome is defined by a new pulmonary infiltrate on chest X-ray accompanied by fever, chest pain, or respiratory distress, and is a leading cause of mortality.
Functional asplenia caused by repeated splenic infarctions increases susceptibility to encapsulated organisms, specifically *Streptococcus pneumoniae*, *Haemophilus influenzae*, and *Neisseria meningitidis*.
Hydroxyurea is the primary disease-modifying therapy used to increase fetal hemoglobin (HbF) levels and reduce the frequency of painful crises.
Transcranial Doppler (TCD) ultrasound is the gold standard screening tool in children aged 2–16 to assess for stroke risk by measuring blood flow velocity in the middle cerebral arteries.
Aplastic crisis is characterized by a sudden drop in hemoglobin and reticulocytopenia, most commonly triggered by Parvovirus B19 infection.
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A 22-year-old male with a history of sickle cell disease presents to the emergency department with severe, diffuse bone pain in his back and extremities. He reports a recent upper respiratory infection. On physical exam, he is febrile, tachycardic, and tachypneic with decreased breath sounds at the right lung base. A chest X-ray reveals a new pulmonary infiltrate in the right lower lobe. His oxygen saturation is 88% on room air.
What is the most likely diagnosis?
Acute Chest Syndrome
The patient presents with the classic triad of fever, respiratory distress, and a new pulmonary infiltrate, which defines Acute Chest Syndrome, a life-threatening complication of vaso-occlusive crisis.
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Etiology / Epidemiology
Autosomal recessive hemoglobinopathy; HbSS genotype. Triggered by hypoxia, dehydration, infection, or cold.
Clinical Manifestations
Acute, severe pain in extremities, chest, or back. Dactylitis in infants; acute chest syndrome.
Diagnosis
Hemoglobin electrophoresis is the gold standard. Peripheral smear shows sickled cells and Howell-Jolly bodies.
Treatment
IV hydration and IV opioids (morphine/hydromorphone). Avoid meperidine due to seizure risk.
Prognosis
High risk of functional asplenia and infection. Prophylactic penicillin required until age 5.
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Epidemiology & Etiology
Prevalent in individuals of African, Mediterranean, and Middle Eastern descent. The condition arises from a point mutation in the beta-globin gene, substituting valine for glutamic acid. Crisis is precipitated by stressors that promote erythrocyte sickling and microvascular occlusion.
Pertinent Anatomy
Vaso-occlusion occurs primarily in the microvasculature of the bone marrow, lungs, and spleen. Repeated infarction leads to autosplenectomy by early childhood, significantly increasing susceptibility to encapsulated organisms.
Pathophysiology
Deoxygenated HbS polymerizes, causing rigid, crescent-shaped red blood cells. These cells adhere to the endothelium, causing vascular stasis and tissue ischemia. The resulting inflammatory cascade exacerbates pain and further promotes sickling, creating a vicious cycle of vaso-occlusion.
Clinical Manifestations
Patients present with acute, severe pain crises often involving the long bones or chest. Dactylitis (hand-foot syndrome) is a common early sign in infants. Acute chest syndrome, defined by new pulmonary infiltrates and fever, is a life-threatening emergency requiring immediate intervention.
Diagnosis
Hemoglobin electrophoresis confirms the diagnosis by identifying the presence of HbS. Peripheral blood smears reveal sickled cells and Howell-Jolly bodies, the latter indicating splenic dysfunction. CBC typically shows chronic hemolytic anemia with elevated reticulocyte counts.
Treatment
Management focuses on IV hydration and aggressive IV opioids for pain control. Meperidine is strictly contraindicated due to the risk of neurotoxicity and seizures. Hydroxyurea is indicated for patients with frequent crises to increase HbF levels. Exchange transfusion is reserved for severe complications like stroke or acute chest syndrome.
Prognosis
Patients are at high risk for sepsis from encapsulated organisms like Streptococcus pneumoniae. Long-term management requires prophylactic penicillin and pneumococcal vaccination to reduce mortality. Regular monitoring for retinopathy and nephropathy is essential.
Differential Diagnosis
Osteomyelitis: localized bone tenderness with fever, usually unilateral
Acute Chest Syndrome: new pulmonary infiltrate on CXR
Aplastic Crisis: sudden drop in hemoglobin with low reticulocyte count
Splenic Sequestration: rapid splenic enlargement with profound anemia
Septic Arthritis: joint effusion with limited range of motion