Sickle Cell Disease, Emergency Medicine

Basics

Description

Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy characterized by abnormal hemoglobin (HbS) which polymerizes under stress and deforms RBCs, resulting in hemolysis, vaso-occlusion, and subsequent tissue ischemia/infarction
HbS production secondary to a single amino acid substitution in hemoglobin gene
Occurs in people of African, Mediterranean, Middle Eastern, and Asian descent; areas where malaria is endemic
Severity variable even among the same phenotype
Genotypes and severity in African Americans:
- HbSS, severe
- HbSC, mild to moderate severity
- HbS ²-thalassemia, mild to moderate severity
- HbAS, sickle cell trait:
  - No manifestation of disease
  - At risk for sudden death with extreme physical exertion, severe hypoxia, severe dehydration, or maternal labor
Chronic hemolytic anemia associated with progressive vasculopathy manifested by systemic and pulmonary hypertension, cholelithiasis, cutaneous leg ulcers, and priapism
Acute vaso-occlusive crisis (VOC) can occur in essentially any organ systems:
- Bone/joint crises:
  - Vaso-occlusion of bone microvasculature causes infarction
  - Long bones, ribs, sternum, spine, and pelvis affected
  - Dactylitis, or "hand " foot syndrome, " occurs at ages 6 " 24 mo
- Acute chest syndrome:
  - Vaso-occlusion of pulmonary vasculature
  - Fat embolism from infarcted bone marrow and/or infections (viral or bacterial) may contribute
  - Associated Chlamydia pneumoniae and Mycoplasma pneumoniae isolated in sputum and Streptococcus pneumoniae bacteremia
  - High mortality (2 " 14%)
  - 50% of sickle cell patients will experience at least 1 episode
  - Radiographic pulmonary infiltrate with fever and respiratory symptoms makes it difficult to distinguish from pneumonia
  - More common in children
- Splenic sequestration:
  - Splenic sinusoids become congested with sickled RBCs, obstructing outflow
  - Estimated 6 " 17% of SCD deaths
  - Circulatory collapse may be rapidly fatal
  - More common in children <5 yr old
- Aplastic crisis:
  - Bone marrow suppression usually occurs secondary to viral infection, most commonly Parvovirus B19
  - Hallmark acute anemia with low reticulocyte count
  - Acute bone marrow suppression significantly worsens chronic anemia
  - Generally self-limited
  - More common in children
- Cerebrovascular accident/transient ischemic attack (CVA/TIA):
  - Secondary to vaso-occlusion by sickled cells and thromboembolism in children and older patients, respectively
  - Children with SCD have a 300-fold increased risk of CVA/TIA
  - Most events occur before the age of 10 and after the age of 29 yr
- Bacterial infection:
  - Sepsis is the leading cause of death in patients with SCD
  - Increased risk of bacteremia, meningitis, and osteomyelitis
  - Impaired splenic function impairs ability to fight encapsulated organisms
  - S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Escherichia coli, and Salmonella are leading organisms
  - Children <5 yr of age have 400-fold increase in pneumococcal infections.
- Priapism:
  - Painful, sustained, unwanted erection >3 hr
  - More commonly low-flow (ischemic) priapism than high-flow (nonischemic)

Acute sickle cell complications in children carry high morbidity and should be screened for aggressively
Infections commonly precipitate crisis
Confirm immunization history (pneumococcal and H. influenzae type b)
Determine if child is receiving prophylactic penicillin, normally indicated in children ≤5 yr old
Overwhelming infection highest in children <3 yr of age

Variable frequency of crisis episodes, not uncommon for increased frequency
Anemia is more profound
Increased rates of hypertensive disorders of pregnancy, asymptomatic bacterial infections, UTI, and pyelonephritis leading to septicemia
Increased risk of spontaneous abortions, antepartum bleeding, and premature rupture of membranes
Increased risk of preterm labor, intrauterine growth restriction, and low birth weight

Etiology

Common crisis precipitants:

Infection (bacterial and viral)
Dehydration
Hypoxemia
Acidosis
Emotional stress
Surgery/trauma
Weather changes
Pregnancy
Toxins

Diagnosis

Signs and Symptoms

May present with either:
- Pain crisis
- Complications of the disease
- Combination of above
May not demonstrate usually autonomic signs of acute pain
Sickle cell pain crisis:
- Bone/joint crisis:
  - Pain in extremities, back, sternum, or joints
  - Variable extremity and joint swelling/warmth
  - Hand " foot syndrome in infants; swelling in hands and feet and a reluctance to walk or use hands
- Abdominal crisis:
  - Abdominal pain without peritonitis
  - Variable nausea, vomiting, diarrhea
- Priapism: Prolonged painful erection
Complications/progression of disease:
- Acute chest syndrome:
  - Chest pain
  - Fever
  - New pulmonary infiltrates on chest radiographs
  - Respiratory symptoms
  - Hypoxemia
- Splenic sequestration crisis:
  - Abdominal pain, splenomegaly
  - Fatigue, lethargy, pallor
  - Hypotension, tachycardia, syncope, shock
- Aplastic crisis:
  - Variable fever, headache, nausea, vomiting
  - Fatigue, pallor, tachycardia
- CVA/TIA:
  - Focal neurologic deficit
  - Mental status changes
  - Seizure

History

Genotype
Onset of current symptoms
Previous crises
Immunizations
Surgical history
Determine typical vs. atypical crisis

Physical Exam
Conduct a thorough physical exam:

Vital signs: BP, HR, temperature, O2 saturation
General appearance: Jaundice, pallor
Cardiopulmonary exam:
- Rales, wheezing, tachypnea
- Peripheral edema, elevated JVD
- Gallops, murmurs
Abdominal exam:
- Organomegaly, tenderness, peritonitis
Musculoskeletal exam
- Erythema on extremities
- Warm, swollen hands and feet in children
Neurologic exam:
- Focal neurologic impairment
- Cranial nerve palsy

Essential Workup

Conduct a thorough physical exam, with focus on signs of infection or ischemia.

Diagnosis Tests & Interpretation

Lab

CBC:
- Compare Hb with prior values if available
- Leukocytosis is common and does not necessarily indicate infection
Reticulocyte count is generally elevated in SCD individuals, and decreased with aplastic crisis
Complete metabolic panel (CMP):
- Be aware that creatinine may appear normal despite baseline chronic renal dysfunction
- Elevated total bilirubin levels may indicate intravascular hemolysis
Markers of hemolysis (total bilirubin, haptoglobin, and LDH) may be present at variable degrees
Serial arterial blood gases and A " a gradients helpful in acute chest syndrome
Cultures: Blood, urine, throat, and CSF (if indicated)
Type and screen (or cross)
Urine pregnancy test in women

Imaging

Radiographs should be directed to confirm diagnosis:
- Chest radiograph if pneumonia or acute chest syndrome suspected
- Extremity radiographs if osteomyelitis suspected
IV contrast may exacerbate or precipitate a crisis
Head CT/MRI to evaluate stroke

Diagnostic Procedures/Surgery

Lumbar puncture if CNS infection or subarachnoid hemorrhage is suspected
Arthrocentesis for acute arthritis

Differential Diagnosis

Sickle cell crises may mimic or obscure more serious underlying pathology (e.g., acute abdomen, MI, PE, nephrolithiasis)
Suspect other diagnoses if pain is more severe or atypical

Treatment

Initial Stabilization/Therapy

Identify and treat high morbidity complications
Establish venous access
Assess pain and initiate therapy

Ed Treatment/Procedures

Choice of analgesics dependent on patient, severity of presentation, and prior agents:
- Reassess pain frequently (e.g., every 15 " 30 min) and titrate until improvement
- IV opiates (e.g., morphine, hydromorphone, fentanyl) 1st line, consider adjunct agents
- Adjuncts: Acetaminophen, NSAIDs (use with caution given impaired renal function)
- Caution with meperidine as metabolites may accumulate and pose seizure risk
- If no venous access, PO and subcutaneous analgesics preferred over IM
Hydration:
- Oral hydration if patient tolerating po
- Parenteral IV solution 0.45% NS for adults and children or 0.2% NS for infants
- Avoid over-hydration, at risk for:
  - Hyperchloremic metabolic acidosis which promotes RBC sickling
  - Atelectasis which precipitates acute chest syndrome
Complication-specific therapy:
- Acute chest syndrome:
  - Oxygen, bronchodilators, incentive spirometer
  - Consider exchange transfusion for worsening respiratory symptoms, hypoxemia, and increasing A " a gradient
- Splenic sequestration:
  - Simple transfusion, promotes remobilization of RBCs
  - Be aware risk of precipitating VOC after raising Hb levels
  - Ideal treatment is prevention: Chronic transfusions, splenectomy
- Aplastic crisis:
  - Simple transfusion
  - Isolation from pregnant healthcare workers
- Priapism:
  - 1st line: Intracavernosal aspiration withα-adrenergic agonist (e.g., epinephrine, terbutaline) irrigation
  - 2nd line: Exchange transfusion if failed aspiration
- Empiric antibiotics: Sepsis, pneumonia, and osteomyelitis
- Exchange transfusion may be required for complications such as CVA and priapism
Consultations:
- Hematology especially if exchange transfusion required
- Neurology/neurosurgery for acute CNS events
- Urology for priapism

Follow-Up

Disposition

Admission Criteria

Refractory pain
Complications: Acute chest syndrome, sequestration crisis, aplastic crisis, CVA/TIA, refractory priapism
Signs of bacterial infection or fever of undetermined etiology
Symptomatic anemia
ICU admission for hemodynamic instability, worsening hypoxemia in acute chest syndrome, and severe acute CNS events.

Discharge Criteria

Resolution of pain crisis
No indications for admission
Follow-up arranged with hematologist

Issues for Referral
Meticulous primary care can limit the frequency and severity of pain crises.

Followup Recommendations

If discharged, patient should see PCP or hematologist in 1 " 2 days.

Pearls and Pitfalls

Distinguish typical sickle cell crisis from acute life-threatening complications
Treat pain aggressively with appropriately selected and administered analgesic agents
Patients with acute pain may not demonstrate typical signs, such as tachycardia or diaphoresis

Additional Reading

Glassberg J. Evidence-based management of sickle cell disease in the emergency department. Emerg Med Pract. 2011;13(8):1 " 20.
Montelambert MD. Management of sickle cell disease. BMJ. 2008;337:626 " 630.
Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376:2018 " 2031.
Rogers DT, Molokie R. Sickle cell disease in pregnancy. Obstet Gynecol Clin North Am. 2010;37:223 " 237.
Wang W, et al. Sickle cell anemia and other sickling syndromes. In: Greer J, ed. Wintrobes Clinical Hematology. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:1038 " 1082.
http://scinfo.org.
http://www.cdc.gov/NCBDDD/sicklecell/index.html.

Codes

ICD9

282.41 Sickle-cell thalassemia without crisis
282.61 Hb-SS disease without crisis
282.63 Sickle-cell/Hb-C disease without crisis
282.5 Sickle-cell trait
282.60 Sickle-cell disease, unspecified
282.62 Hb-SS disease with crisis
282.64 Sickle-cell/Hb-C disease with crisis
282.68 Other sickle-cell disease without crisis
282.69 Other sickle-cell disease with crisis
282.6 Sickle-cell disease

ICD10

D57.1 Sickle-cell disease without crisis
D57.20 Sickle-cell/Hb-C disease without crisis
D57.40 Sickle-cell thalassemia without crisis
D57.3 Sickle-cell trait
D57.00 Hb-SS disease with crisis, unspecified
D57.219 Sickle-cell/Hb-C disease with crisis, unspecified
D57.419 Sickle-cell thalassemia with crisis, unspecified
D57.80 Other sickle-cell disorders without crisis
D57.819 Other sickle-cell disorders with crisis, unspecified

SNOMED

127040003 Hereditary hemoglobinopathy disorder homozygous for hemoglobin S (disorder)
417683006 Sickle cell-hemoglobin C disease without crisis
417048006 Sickle cell-thalassemia disease without crisis (disorder)
16402000 Sickle cell trait (disorder)
416826005 Sickle cell-thalassemia disease with crisis (disorder)
417425009 Hemoglobin SS disease with crisis (disorder)
417517009 Sickle cell-hemoglobin C disease with crisis

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