• Patients experiencing a sickle cell crisis (SCC) are often in severe pain and benefit from analgesia within 60 minutes of presentation.
• SCC is a diagnosis of exclusion — anchoring bias predisposes sickle cell disease (SCD) patients to underdiagnosis of non-SCD-related conditions.

• SCD is an autosomal recessive disorder characterized by deformed red blood cells and acute SCCs.
• An uncomplicated sickle cell pain crisis is also called a vaso-occlusive crisis.
• SCD can also lead to severe complications such as acute chest syndrome, stroke, aplastic crisis and splenic sequestration crisis.

Do not rule out SCC on the basis of physical appearance.

• SCD affects over 6500 Canadians.
• Although SCD has a higher prevalence in Black and Hispanic populations, it can affect anyone.
• Patients with SCC may not appear in pain due to having learned to adapt to it during the course of their lives.

Patients experiencing SCC should receive analgesia within 60 minutes of presentation.

• SCD is a lifelong illness and patients experienced in managing their condition.
• Those presenting to the ED may appear to be in less pain than they truly are.
• Studies have demonstrated inadequate and/or untimely management of SCC pain due to negative provider attitudes and a fear that patients are drug-seeking.
• In fact, the rate of opioid use disorder (OUD) in sickle cell disease (SCD) patients is the same as the general population.

• SCC is a clinical diagnosis of exclusion.
• A broad differential should include non-SCD emergencies related to the relevant anatomical site, SCC and its complications.

Non-SCD Emergencies

• Standard workups should be applied to SCD patients to rule out life-threatening conditions.
• Patients with SCD are at particularly increased risk of developing the following conditions:
  • Infection (d/t impaired splenic function).
  • Pulmonary hypertension (6-10% prevalence).
  • Acute renal failure incidence (1.4% vs 0.4% in baseline population).
  • Chronic kidney disease incidence (1.3% vs 0.6% in baseline population).
  • Liver disease (as high as 30% prevalence in autopsy studies).

Note: Some reports suggest SCD is not associated with an increased prevalence of CAD, as conventionally believed.

Stroke

• SCD patients are at increased risk of stroke due to sickled RBCs causing cerebrovascular vaso-occlusion.
• Up to 11% of children and 24% of adults with SCD may experience a stroke.
• Stroke must be ruled out in all SCD patients presenting with focal neurological deficits, including pediatric patients not typically evaluated for stroke.
• Initial investigations include: CBC + diff, reticulocyte count, type and cross match, HbS%, PT, PTT.

Infection

• Many adult SCD patients are functionally or physically asplenic.
• These patients are at greater risk of infection due to a number of reasons, including: splenic and neutrophil dysfunction, reduced opsonization of encapsulated organisms, decreased humoral immunity and others.

Uncomplicated SCC (Vaso-Occlusive Crisis, Sickle Pain Crisis)

• Acute pain crisis that occurs as a result of sickled RBCs forming heterocellular aggregates on endothelial walls.
• This leads to small vessel occlusion and local hypoxia.
• Can affect any part of the body but often involves extremities, chest and back.
• Children often present with swelling of the hands and feet.
• Vaso-occlusive crisis is a diagnosis of exclusion and should only be made if other complications have been ruled out.

SCC Complications

Splenic Sequestration Crisis

• Occurs as a result of sickled RBCs vaso-occluding the splenic microvasculature.
• As RBCs sequester, they continue to be deoxygenated and sickled, causing fibrosis of the spleen.
• The accumulation of blood often leads to splenomegaly and associated pain.
• Typically occurs in young children ages 2 months to 4 years, or older children with milder forms of the disease (Sickle C disease or Sickle beta-plus thalassemia).
• Often presents with the following:
  • General signs of anemia (pallor, weakness, tachycardia, tachypnea).
  • Massive splenomegaly (usually with abdominal discomfort/distention).
  • Low Hgb.
  • High reticulocyte counts.

Aplastic Crisis

• Occurs as a result of erythropoiesis suppression by human parvovirus B19.
• As the half life of sickle RBCs is already reduced (12-15 days), viral suppression of erythropoiesis can result in a marked decrease in Hgb and reticulocytes (aplastic crisis).
• Often presents with the following:
  • General signs of anemia (pallor, weakness, tachycardia, tachypnea).
  • Low Hgb.
  • Low/non-existent reticulocyte count.

Acute Chest Syndrome

• Occurs as a result of sickled RBCs vaso-occluding the pulmonary vasculature.
• As RBCs sequester, they continue to be deoxygenated and sickled causing further vaso-occlusion, as well as ischemia and endothelial damage.
• ~40% of cases are attributable to an inciting event, most commonly a vaso-occlusive crisis.
• Any patient with SCC and signs of hypoxemia should be presumed to have Acute Chest Syndrome until proven otherwise.
• Most common cause of death in SCD patients.
• Most common in 2-4 year olds and during winter months.
• ~50% of SCD patients will develop Acute Chest Syndrome within their lifetime.
• ~50% of Acute Chest Syndrome episodes will occur during hospitalization of another condition (most often uncomplicated SCC).
• Diagnosis is made via physical exam, chest x-rays (CXR) and bloodwork.
• 35% of patients present with a normal physical exam.
• Common symptoms include: fever, cough, chest pain, dyspnea, chills, wheezing and hemoptysis.
• Symptoms may mimic those of pneumonia or PE but these are usually inciting events that cause acute chest syndrome.
• Infiltrates on CXR may not appear for 2-3 days.
• Patients with uncomplicated SCC accompanied by chest/respiratory symptoms should have repeat CXR performed 24-48h after the start of their episode.
• In adults with SCC, a decrease in platelet count of ≥ 10% is strongly predictive of development of Acute Chest Syndrome.

Other Complications

• SCD can contribute and lead to a number of other complications, including:
  • Sickle retinopathy.
  • Heart failure with preserved ejection fraction.
  • Avascular necrosis of bones.
  • Priapism.
  • Dental complications.

Note: The purpose of this review is not to discuss all of these complications in depth, but highlight the pervasiveness of this disease and its multi-organ complications. Providers should remain vigilant for these conditions in SCD patients presenting with seemingly unassociated symptoms.

Blood Transfusions

• Exchange transfusions are a key intervention for the management of SCD complications by removing the patient’s sickled RBCs and replacing them with non-sickled donor RBCs.
• Simple transfusions do not remove the patient’s sickled RBCs, so their use is limited to specific applications.
• Hematology should be consulted for all transfusions due to the risk of complications and increased alloimmunization.
• Consider specifically advising the blood bank before transfusions in SCD patients.

Non-SCD Emergencies

• The management of non-SCD emergencies is the same as in non-SCD patients.

Uncomplicated SCC

• The cornerstone of SCC therapy is pain management and supportive therapy.
• Clinicians often under-dose analgesics.
• If the patient uses opioid medications at home, start with their total daily dose in a single dose IV.
• Hydromorphone/morphine may be administered q15-30min for pain control.
• Ketamine is an effective second-line agent when opioids have been unsuccessful.
• Corticosteroids increase the risk of pain recurrence and are not recommended for routine use.
• There is no role for supplemental O2 if O2 saturation is > 92%.
• There is no role for fluid boluses unless the patient is overtly hypovolemic.
• Resuscitation should be performed only to euvolemia and maintenance performed with hypotonic solution.
• There is no role for blood transfusions and when performed unnecessarily can cause increased pain.
• Consider discussing the role of hydroxyurea with patients not currently on medication.
• Reserve the prescription of hydroxyurea for the patient’s hematologist, who has better longitudinal follow-up with the patient.

SCC Complications

Splenic Sequestration Crisis

• Minor episodes of splenic sequestration crisis may be managed with RBC transfusions.
• Patients with severe and/or recurrent crises may be offered a partial or total splenectomy.
• Pain management and supportive therapy should be initiated as in uncomplicated crises.

Aplastic Crisis

• Urgent hematology referral is warranted.
• Urgent red blood cell transfusions are warranted in patients with aplastic crisis.
• Pain management and supportive therapy should be initiated as in uncomplicated crises.

Acute Chest Syndrome

• Urgent hematology referral is warranted.
• Urgent RBC transfusions or exchange transfusions are warranted in patients with aplastic crisis.
• Indications for exchange transfusion instead of simple RBC transfusion include:
  • Severe ACS
  • Rapid clinical deterioration
  • Worsening CXR
  • PO2 < 70mmHg
  • Baseline Hgb > 90
  • Pain management and supportive therapy should be initiated as in uncomplicated crises.

Stroke

• Urgent hematology and neurology referral is warranted.
• Initial management involves exchange transfusion rather than thrombolysis.
• Secondary prevention often involves monthly simple transfusions but should be managed by the patient’s hematologist.

• Patients with complications of SCC.
• Patients requiring transfusions.
• Patients who are hemodynamically unstable.
• Patients in whom pain has not been adequately controlled.
• Patients with SCC in whom impending development of Acute Chest Syndrome is suspected.

• Inability to meet requirements for transfusions and/or hematology referral not in-house.

• Hematology referral is warranted in any case of complicated SCC.
• Hematology referral is warranted for patients initiating hydroxyurea medication.
• Hematology and neurology referral is warranted for patients with SCD and symptoms of stroke.

• Patients with uncomplicated SCC, in whom complications have been ruled out and pain managed appropriately, may be safely discharged home.
• Given that half of Acute Chest Syndrome cases emerge from uncomplicated SCC, patients should be advised to return to hospital if their pain worsens or they develop any new symptoms.

1. Emergency Management of Sickle Cell Disease Podcast:

   https://podcasts.apple.com/ca/podcast/emergency-medicine-cases/id411665520?i=1000349977330

   
   

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2. Glassberg JA. Improving Emergency Department-Based Care of Sickle Cell Pain. Hematology Am Soc Hematol Educ Program. 2017;2017(1): 412-417. Available from: https://ashpublications.org/hematology/article/2017/1/412/21059/Improving-Emergency-Department-Based-Care-of

   
   

3. Telfer P & Kaya B. Optimizing the care model for an uncomplicated acute pain episode in sickle cell disease. Hematology Am Soc Hematol Educ Program. 2017;2017(1): 525-533. Available from: https://ashpublications.org/hematology/article/2017/1/525/21204/Optimizing-the-care-model-for-an-uncomplicated

   
   

4. Kassim AA, Galadanci NA, Pruthi S, DeBaun MR. How I treat and manage strokes in sickle cell disease. Blood. 2015;125(22): 3401-3410. Available from: https://ashpublications.org/blood/article/125/22/3401/34343/How-I-treat-and-manage-strokes-in-sickle-cell

   
   

5. Martinez RM, Osei-Anto HA, McCormick M. Complications of Sickle Cell Disease and Current Management Approaches [Internet]. www.ncbi.nlm.nih.gov. National Academies Press (US). 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK566466/