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Sickle Cell Disease, Emergency Medicine

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Sickle Cell Disease, Emergency Medicine

Basics

Description

Conduct a thorough physical exam:

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

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

  • 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, severeHbSC, mild to moderate severityHbS Ž ²-thalassemia, mild to moderate severityHbAS, sickle cell trait:No manifestation of diseaseAt 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 infarctionLong bones, ribs, sternum, spine, and pelvis affectedDactylitis, or "hand " “foot syndrome, "  occurs at ages 6 " “24 moAcute chest syndrome:Vaso-occlusion of pulmonary vasculatureFat embolism from infarcted bone marrow and/or infections (viral or bacterial) may contributeAssociated Chlamydia pneumoniae and Mycoplasma pneumoniae isolated in sputum and Streptococcus pneumoniae bacteremiaHigh mortality (2 " “14%)50% of sickle cell patients will experience at least 1 episodeRadiographic pulmonary infiltrate with fever and respiratory symptoms makes it difficult to distinguish from pneumoniaMore common in childrenSplenic sequestration:Splenic sinusoids become congested with sickled RBCs, obstructing outflowEstimated 6 " “17% of SCD deathsCirculatory collapse may be rapidly fatalMore common in children <5 yr oldAplastic crisis:Bone marrow suppression usually occurs secondary to viral infection, most commonly Parvovirus B19Hallmark acute anemia with low reticulocyte countAcute bone marrow suppression significantly worsens chronic anemiaGenerally self-limitedMore common in childrenCerebrovascular accident/transient ischemic attack (CVA/TIA):Secondary to vaso-occlusion by sickled cells and thromboembolism in children and older patients, respectivelyChildren with SCD have a 300-fold increased risk of CVA/TIAMost events occur before the age of 10 and after the age of 29 yrBacterial infection:Sepsis is the leading cause of death in patients with SCDIncreased risk of bacteremia, meningitis, and osteomyelitisImpaired splenic function impairs ability to fight encapsulated organismsS. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Escherichia coli, and Salmonella are leading organismsChildren <5 yr of age have 400-fold increase in pneumococcal infections.Priapism:Painful, sustained, unwanted erection >3 hrMore commonly low-flow (ischemic) priapism than high-flow (nonischemic)
  • HbSS, severe
  • HbSC, mild to moderate severity
  • HbS Ž ²-thalassemia, mild to moderate severity
  • HbAS, sickle cell trait:No manifestation of diseaseAt risk for sudden death with extreme physical exertion, severe hypoxia, severe dehydration, or maternal labor
  • No manifestation of disease
  • At risk for sudden death with extreme physical exertion, severe hypoxia, severe dehydration, or maternal labor
  • Bone/joint crises:Vaso-occlusion of bone microvasculature causes infarctionLong bones, ribs, sternum, spine, and pelvis affectedDactylitis, or "hand " “foot syndrome, "  occurs at ages 6 " “24 mo
  • Acute chest syndrome:Vaso-occlusion of pulmonary vasculatureFat embolism from infarcted bone marrow and/or infections (viral or bacterial) may contributeAssociated Chlamydia pneumoniae and Mycoplasma pneumoniae isolated in sputum and Streptococcus pneumoniae bacteremiaHigh mortality (2 " “14%)50% of sickle cell patients will experience at least 1 episodeRadiographic pulmonary infiltrate with fever and respiratory symptoms makes it difficult to distinguish from pneumoniaMore common in children
  • Splenic sequestration:Splenic sinusoids become congested with sickled RBCs, obstructing outflowEstimated 6 " “17% of SCD deathsCirculatory collapse may be rapidly fatalMore common in children <5 yr old
  • Aplastic crisis:Bone marrow suppression usually occurs secondary to viral infection, most commonly Parvovirus B19Hallmark acute anemia with low reticulocyte countAcute bone marrow suppression significantly worsens chronic anemiaGenerally self-limitedMore common in children
  • Cerebrovascular accident/transient ischemic attack (CVA/TIA):Secondary to vaso-occlusion by sickled cells and thromboembolism in children and older patients, respectivelyChildren with SCD have a 300-fold increased risk of CVA/TIAMost 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 SCDIncreased risk of bacteremia, meningitis, and osteomyelitisImpaired splenic function impairs ability to fight encapsulated organismsS. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Escherichia coli, and Salmonella are leading organismsChildren <5 yr of age have 400-fold increase in pneumococcal infections.
  • Priapism:Painful, sustained, unwanted erection >3 hrMore commonly low-flow (ischemic) priapism than high-flow (nonischemic)
  • 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
  • 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 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
  • 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
  • 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
  • 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.
  • 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

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

Diagnosis

Signs and Symptoms

  • May present with either:Pain crisisComplications of the diseaseCombination of above
  • May not demonstrate usually autonomic signs of acute pain
  • Sickle cell pain crisis:Bone/joint crisis:Pain in extremities, back, sternum, or jointsVariable extremity and joint swelling/warmthHand " “foot syndrome in infants; swelling in hands and feet and a reluctance to walk or use handsAbdominal crisis:Abdominal pain without peritonitisVariable nausea, vomiting, diarrheaPriapism: Prolonged painful erection
  • Complications/progression of disease:Acute chest syndrome:Chest painFeverNew pulmonary infiltrates on chest radiographsRespiratory symptomsHypoxemiaSplenic sequestration crisis:Abdominal pain, splenomegalyFatigue, lethargy, pallorHypotension, tachycardia, syncope, shockAplastic crisis:Variable fever, headache, nausea, vomitingFatigue, pallor, tachycardiaCVA/TIA:Focal neurologic deficitMental status changesSeizure
  • Pain crisis
  • Complications of the disease
  • Combination of above
  • Bone/joint crisis:Pain in extremities, back, sternum, or jointsVariable extremity and joint swelling/warmthHand " “foot syndrome in infants; swelling in hands and feet and a reluctance to walk or use hands
  • Abdominal crisis:Abdominal pain without peritonitisVariable nausea, vomiting, diarrhea
  • Priapism: Prolonged painful erection
  • 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 pain without peritonitis
  • Variable nausea, vomiting, diarrhea
  • Acute chest syndrome:Chest painFeverNew pulmonary infiltrates on chest radiographsRespiratory symptomsHypoxemia
  • Splenic sequestration crisis:Abdominal pain, splenomegalyFatigue, lethargy, pallorHypotension, tachycardia, syncope, shock
  • Aplastic crisis:Variable fever, headache, nausea, vomitingFatigue, pallor, tachycardia
  • CVA/TIA:Focal neurologic deficitMental status changesSeizure
  • Chest pain
  • Fever
  • New pulmonary infiltrates on chest radiographs
  • Respiratory symptoms
  • Hypoxemia
  • Abdominal pain, splenomegaly
  • Fatigue, lethargy, pallor
  • Hypotension, tachycardia, syncope, shock
  • Variable fever, headache, nausea, vomiting
  • Fatigue, pallor, tachycardia
  • Focal neurologic deficit
  • Mental status changes
  • Seizure
  • Genotype
  • Onset of current symptoms
  • Previous crises
  • Immunizations
  • Surgical history
  • Determine typical vs. atypical crisis
  • Vital signs: BP, HR, temperature, O2 saturation
  • General appearance: Jaundice, pallor
  • Cardiopulmonary exam:Rales, wheezing, tachypneaPeripheral edema, elevated JVDGallops, murmurs
  • Abdominal exam:Organomegaly, tenderness, peritonitis
  • Musculoskeletal examErythema on extremitiesWarm, swollen hands and feet in children
  • Neurologic exam:Focal neurologic impairmentCranial nerve palsy
  • Rales, wheezing, tachypnea
  • Peripheral edema, elevated JVD
  • Gallops, murmurs
  • Organomegaly, tenderness, peritonitis
  • Erythema on extremities
  • Warm, swollen hands and feet in children
  • Focal neurologic impairment
  • Cranial nerve palsy

Essential Workup

Diagnosis Tests & Interpretation

  • CBC:Compare Hb with prior values if availableLeukocytosis 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 dysfunctionElevated 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
  • Compare Hb with prior values if available
  • Leukocytosis is common and does not necessarily indicate infection
  • Be aware that creatinine may appear normal despite baseline chronic renal dysfunction
  • Elevated total bilirubin levels may indicate intravascular hemolysis
  • Radiographs should be directed to confirm diagnosis:Chest radiograph if pneumonia or acute chest syndrome suspectedExtremity radiographs if osteomyelitis suspected
  • IV contrast may exacerbate or precipitate a crisis
  • Head CT/MRI to evaluate stroke
  • Chest radiograph if pneumonia or acute chest syndrome suspected
  • Extremity radiographs if osteomyelitis suspected
  • 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 improvementIV opiates (e.g., morphine, hydromorphone, fentanyl) 1st line, consider adjunct agentsAdjuncts: Acetaminophen, NSAIDs (use with caution given impaired renal function)Caution with meperidine as metabolites may accumulate and pose seizure riskIf no venous access, PO and subcutaneous analgesics preferred over IM
  • Hydration:Oral hydration if patient tolerating poParenteral IV solution 0.45% NS for adults and children or 0.2% NS for infantsAvoid over-hydration, at risk for:Hyperchloremic metabolic acidosis which promotes RBC sicklingAtelectasis which precipitates acute chest syndrome
  • Complication-specific therapy:Acute chest syndrome:Oxygen, bronchodilators, incentive spirometerConsider exchange transfusion for worsening respiratory symptoms, hypoxemia, and increasing A " “a gradientSplenic sequestration:Simple transfusion, promotes remobilization of RBCsBe aware risk of precipitating VOC after raising Hb levelsIdeal treatment is prevention: Chronic transfusions, splenectomyAplastic crisis:Simple transfusionIsolation from pregnant healthcare workersPriapism:1st line: Intracavernosal aspiration withα-adrenergic agonist (e.g., epinephrine, terbutaline) irrigation2nd line: Exchange transfusion if failed aspirationEmpiric antibiotics: Sepsis, pneumonia, and osteomyelitisExchange transfusion may be required for complications such as CVA and priapism
  • Consultations:Hematology especially if exchange transfusion requiredNeurology/neurosurgery for acute CNS eventsUrology for priapism
  • 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
  • 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 sicklingAtelectasis which precipitates acute chest syndrome
  • Hyperchloremic metabolic acidosis which promotes RBC sickling
  • Atelectasis which precipitates acute chest syndrome
  • Acute chest syndrome:Oxygen, bronchodilators, incentive spirometerConsider exchange transfusion for worsening respiratory symptoms, hypoxemia, and increasing A " “a gradient
  • Splenic sequestration:Simple transfusion, promotes remobilization of RBCsBe aware risk of precipitating VOC after raising Hb levelsIdeal treatment is prevention: Chronic transfusions, splenectomy
  • Aplastic crisis:Simple transfusionIsolation from pregnant healthcare workers
  • Priapism:1st line: Intracavernosal aspiration withα-adrenergic agonist (e.g., epinephrine, terbutaline) irrigation2nd line: Exchange transfusion if failed aspiration
  • Empiric antibiotics: Sepsis, pneumonia, and osteomyelitis
  • Exchange transfusion may be required for complications such as CVA and priapism
  • Oxygen, bronchodilators, incentive spirometer
  • Consider exchange transfusion for worsening respiratory symptoms, hypoxemia, and increasing A " “a gradient
  • Simple transfusion, promotes remobilization of RBCs
  • Be aware risk of precipitating VOC after raising Hb levels
  • Ideal treatment is prevention: Chronic transfusions, splenectomy
  • Simple transfusion
  • Isolation from pregnant healthcare workers
  • 1st line: Intracavernosal aspiration withα-adrenergic agonist (e.g., epinephrine, terbutaline) irrigation
  • 2nd line: Exchange transfusion if failed aspiration
  • Hematology especially if exchange transfusion required
  • Neurology/neurosurgery for acute CNS events
  • Urology for priapism

Follow-Up

Disposition

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

Followup Recommendations

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.

See Also (Topic, Algorithm, Electronic Media Element)

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