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Sickle Cell Disease

• Simple Facts about Sickle Cell
• Fever Management
• Chronic Problems
• Pregnancy
• Pain Management
• Acute Chest Syndrome
• Splenic Sequestration
• Stroke Intervention
• Aplastic Crisis & Intervention
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• Transfusion Therapy
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Fever Evaluation & Management Intervention

Infection is the most common cause of death in children with sickle cell disease.  The risk of pneumococcal sepsis is 400 times greater in young children with sickle cell disease.  Infection with Hemphilius influenzae sepsis is up to 4 times as common (Oski p674).   This is due to splenic dysfunction involving both the clearance of particles from the intravasculature and impaired antibody synthesis.  There is decreased ability of the spleen to filter encapsulated bacteria due to vascular obstruction causing diversionary blood flow away from the phagocytic areas ( Whitten, GLaRGG, p6).  In general, the organisms causing infection in this population are common.  The most common causes of infections in sickle cell diseas are  (in order of frequency): Streptococcus pneumoniae, Hemophilus influenzae, Neisseria, Salmonella, Mycoplasma, Staphyloccus aureus, Escherichia coli, and Streptococcus pyogenes. (Oski  p671)  The most common infection types and etiologies are listed below:

Infection        Organism            Frequency

Pneumonia      No bacterial confirmation          82%

Pneumococci            7%

Enteric gram-negative rods    4%

Staphyloccus aureus        1%

Mycoplasma            1%

other                5%

Megitis        Pneumococci            57%

Hemophilus influenzae        8%

Partially treated            21%

other                6%

Aseptic                6%

Urry Tract        Escherichia coli            63%

Klebsiella            27%

Proteus                4%

other                8%

Pneumococci             40%

Hhilus influenzae        11%

Grnegative enterics         11%

Sanella             11%

Sylococcus aureus         8%

Anobic bacteria         8%

Stylococcus  pyogenes         4%

Osmyelitis        Salmonella            70%

Staphylococcus aureus        5%

Pneumococci            15%

Infections cause more morbidity, disseminate more rapidly, and are more difficult to irradicate in persons with sickle cell disease.  Infections can precipitate aplastic crisis and exacerbate hemolytic events as well as precipitate vaso-occlusive painful episodes.

Recommended prevention/immunization: Children with sickle cell disease show normal antibody response to live and killed vaccines.

Birth to 1 month:  Hepatitis B #1
2 months:  DtaP or DTP #1, IPV#1, Hib, Hep B #2
4 months:  DPT#2, IPV#2, Hib
6 months:  DPT #3, Hep B#3, Hib, Pneumococcal vaccine (optional)
15 months:  MMR #1, DPT, OPV booster, Varicella (optional)
18 months: Haemophilus b conjugate
24 months:  Pneumococcal polysaccharide vaccine

 >24 months: meningococcal polysaccharide antigen vaccine (optional)
Yearly influenza virus vaccines
5 years:  Pneumococcal booster (meningococcal booster optional)
11 years:  MMR booster, Hep B (optional), Varicella booster (optional)
15 years (and every 10 years):  Tetanus booster (DT)

Hib, Pneumovax, and Meningiococcal boosters may also be given >2 weeks prior to surgical splenectomy.

Antibiotic prophylaxis with Penicillin has been shown to be effective in preventing life-threatening pneumococcal infections in children with sickle cell disease between age 3 months and 5 years. The usual dose of oral PCN is 125 mg BID until age 3 years, then 250 mg BID.

For PCN allergic patients, use erythromycin 250mg BID.  Amoxicillin is not a good choice due to unproved efficacy, increased side effects, and increased risk for development of resistant organisms. 

(Red Book)
Fever management for the child with sickle cell disease:
The fever accompanying septicemia in these patients is usually >102 F (39 degrees C).  Often the temp rises quickly, and clinical deterioration can occur rapidly.  Administration of IV antibiotics should not be delayed while awaiting lab results.  Blood, throat, and urine cultures should be obtained, and an antibiotic effective against S. pneumoniae, H. influenza, and other encapsulated, rapidly multiplying organisms such as cefuroxime (100mg/kg/24 hr) or cefotaxime should be used.  Lumbar puncture should be done for symptoms of meningitis.  These patients should be admitted to the hospital.  Culture positive sepsis requires 7 days of IV antibiotic therapy (from 1st negative culture), and for meningitis, at least 10 days.

For lower grade fever, an alternative to hospitalization is to obtain CBC and cultures, administer a long-acting antibiotic like ceftriaxone and observe the patient in the clinic or ER for several hours.  Household contacts of children infected with H. influenzae should receive prophylaxis even if they have previously received the H. influenzae vaccine.

Treating infections in adults with sickle cell disease:
Pneumococcal infections are less common after the school-age years.  Infections in adults tend to occur in areas of the body damaged by recurrent sickling such as the lungs, kidneys, or bones.  Even mild infections have the potential to worsen rapidly in routine settings.  Low grade fever (<101) often accompanies vaso-occlusive pain episodes, but infection must always be ruled out.

Pyelonephritis can be difficult to treat, recur regularly, and can often be associated with septicemia.  Sickling in the renal papillae leads to necrosis and increased risk of infection.  This is especially a risk during pregnancy.  Treatment consists of antibiotics and hydration. For severe cases,  in-patient IV cephalosporin and/or aminoglycoside therapy is indicated.

Osteomyelitis can often be difficult to distinguish from diaphyseal bone infarcts.  Blood and stool cultures should be obtained at the same time as a bone aspiration for culture looking for Salmonella, staphylococci, or other enteric organisms.  Tuberculosis should also be ruled out.

Antibiotic resistant Salmonella can be a problem, so even if in vitro susceptibility tests suggest efficacy for tetracyclines, cephalosporins, or aminoglycosides, most practitioners recommend use of trimethoprim-sulfamethoxizole, ampicillin, or chloramphenicol. Salmonella produces chronic intracellular infections and requires prolonged administration of antibiotics (4-6 weeks). Typical treatment would be with IV Ampicillin 150mg/kg/d in 4 divided doses for 21-42 days, followed by oral Ciprofloxacin. If Chloramphenicol is used, careful monitoring for bone marrow suppression and reticulocytopenia should be done.
Staphylococcal osteomyelitis requires high-dose beta lactamase resistant penicillin (IV Nafcillin) for several weeks.  Surgical debridement may also be indicated. (NIH p13-14).