• Watch out for Streptococcus pneumoniae sepsis! Patients can look well for several hours, then suddenly decline, leading to shock or death.
• Note that nearly half of patients with HgSS will have diminished spleen function by 1 year of age
• Start antibiotics early, even if patients are immunized or are taking prophylactic penicillin
• Antibiotic recommendations: long-acting cephalosporin +/- Vancomycin 
• Order CBC, reticulocyte count, blood culture, CXR, and other testing as needed based on presentation
• Admit patients with high fever, toxic appearance, infiltrate on CXR, hypoxia, tachypnea not explained by fever, poor intake/dehydration, severely abnormal CBC, history of S. pneumoniae sepsis, pain crisis + fever

References

Miller, Scott and Kusum Viswanathan. "Sickle Cell Anemia with Fever." Atlas of Pediatric Emergency Medicine, 3rd Edition, edited by Binita Shah, McGraw-Hill, 2019, 510-511.