Sickle Cell Pain

Jeffrey Glassberg

Patricia Shi

Epidemiology

Sickle cell disease (SCD) affects nearly 100,000 individuals in the United States.
The most common reason for emergency department (ED) visits in this population is vaso-occlusive crisis (VOC).
- Second most common reason for ED visits is fever.
In both the ED and inpatient setting, pain is often undertreated.

Pathophysiology

A point mutation at codon 6 of the β-globin gene causes production of abnormal hemoglobin called hemoglobin-S.
When both inherited β-globin genes carry this mutation, or the hemoglobin S mutation is paired with another mutation (hemoglobin C and β-thalassemia are the most common), the patient will have SCD.
In response to tissue hypoxia and stress response, HbS forms rigid polymers, which give erythrocytes their sickle shape.
The pathophysiology of SCD and its complications are due to many factors including:
- Enhanced leukocyte activation
- Increased platelet activation
- Blood cell adhesion
- Endothelial dysfunction
- Chronic hemolysis
The clinical manifestations are myriad and include:
- VOC
- Acute chest syndrome (ACS)
- Splenic or hepatic sequestration
- Stroke
- Aplastic crises
- Dactylitis
- Priapism
- Leg ulcers
- Increased infection risk – rule out sepsis with fever
- Avascular necrosis
- Bony infarcts and osteomyelitis
- Retinopathy
- Pulmonary hypertension
The most common manifestation is pain (VOC).
Most patients experience daily pain, with the most common sites being the lower back and legs.
- Pain can also progress to VOC where the severity of pain requires high-dose opiates, usually necessitating hospital admission.

Potentially Life-Threatening Causes

In a patient presenting with pain, all the non-SCD-related, life-threatening causes of pain in that region must be considered (e.g., right lower quadrant pain in a patient with SCD is still appendicitis until proven otherwise).

Acute Chest Syndrome

It is a serious pulmonary complication, and should be considered in any sickle cell patient presenting with chest pain.
Overall incidence of 10.5 per 100 patient years.
Most common in the 2–4 years age group.
ACS is defined as new infiltrate on chest x-ray with one of the following:
- Chest pain
- Fever
- Respiratory symptoms – dyspnea, tachypnea
- Hypoxia
While ACS criteria are not distinguishable from the definition of pneumonia, it is described as a specific entity because:
- The cause of ACS is not always infection.
- Etiology is multifactorial:
  - Microbial infection
  - Vaso-occlusion
  - Fat embolism from ischemic/necrotic bone marrow
  - Thromboembolism
- The treatment for ACS is transfusion or exchange transfusion. Without this, clinical status often deteriorates rapidly with very high mortality.
Pearl: ACS is usually not the presenting complaint. More commonly, it develops during the course of in-patient admission. Assess frequently for signs and symptoms of ACS.
Management:
- Supportive measures – oxygen.
- Appropriate hydration – avoid bolus of fluids. Consider maintenance fluids without risking overhydration.
- Appropriate pain control.
- Incentive spirometry.
- Antibiotics: third-generation cephalosporin, macrolides.
- Simple or exchange transfusion.

Vaso-occlusive Crisis