About the Condition

Description/definition:

A vaso-occlusive crisis (VOC) (also known as sickle cell pain crisis) is the hallmark acute complication for individuals with sickle cell disease (SCD) and presents as acute severe pain, typically of sudden onset affecting the
extremities, chest and back. Nearly all individuals affected by SCD will experience a VOC during their lifetime. Individuals with more than three hospitalizations for a VOC in a year are at an increased risk of early death.

VOC is the most common cause of presentation to the emergency room and hospitalization (about 95% of cases) among those with SCD.

Persons with the genotypes HbSS or HbSβ0-thalassemia are likely to experience more frequent VOCs. Persons with HbAS (commonly referred to as sickle cell trait) do not experience typical VOCs.

Triggers include:

• Hypoxia
• Daytime exertion
• Waking up earlier with a shortened duration of sleep
• Stress
• Fatigue
• Exercise
• Exposure to cold
• Ingestion of alcohol
• Airline travel
• Altitude that exceeds 2,000 feet
• Infection
• Menstruation
• Pregnancy
• Acidosis

Pathophysiology:

In sickle cell crisis, increased polymerization of sickle hemoglobin leads to increased sickling of red cells, which in turn results in occlusion of small blood vessels. Vaso-occlusion leads to distal tissue ischemia as well as ischemia-reperfusion injury. A variety of inflammatory mediators are generated by tissue and organ injury. These include substances produced by damaged tissue, substances of vascular origin, as well as substances released by nerve fibers and various immune cells.

The inflammatory mediators activate local pain receptors and nerve terminals and produce hypersensitivity in the area of injury, especially in bone and bone marrow. Activity of the mediators results in the excitation of pain receptors in the skin, ligaments, muscle, nerves, and joints. Excitation of these pain receptors stimulates the specialized nerves e.g., C fibers and A-delta fibers that carry pain impulses to the spinal cord and brain.

As pain increases in severity, chest splinting leads to regional hypoventilation, hypoxemia, and increased sickling of the red blood cells (RBCs). There is upregulation of adhesion molecules, causing interaction of these rigid, polymerized sickled RBCs to the endothelium. The increased adhesion of erythrocytes followed by the formation of heterocellular aggregates physically causes small vessel occlusion and resultant local hypoxia.

This process triggers a vicious cycle of increased HbS formation and the release of inflammatory mediators and free radicals that contribute to reperfusion injury, increased pain, increased hypoventilation, and increased sickling.

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Clinical presentation:

• The pain associated with VOC is often described as:
  • Sudden in onset
  • Throbbing
  • Sharp
• Often occurs at night, due to the relative hypoxia as a result of varying degrees of sleep apnea, or due to a trigger the patient may have been exposed to during the day.
• Typically begins as localized pain (often single joint or the spine) and then spreads over multiple bones and joints as well as the spine.
• Common sites of pain include the extremities, joints, chest, and lower back.
• The frequency, severity, location, and duration of pain vary among patients and longitudinally in the same patient.
• Most patients present with neither obvious precipitating factors nor objective signs.
• May present with low-grade fever, mild decrease in Hb, increased leukocyte count, increased lactate dehydrogenase, and increased reticulocyte count, but may also present with normal vital signs and hematologic parameters unchanged from baseline.

Diagnosis:

There are no specific tests to rule in or rule out a VOC; it is important to rule out other causes of pain, including:

• Acute chest syndrome
• Acute abdomen:
  • Acute appendicitis
  • Acute pancreatitis
  • Acute pyelonephritis
  • Pelvic inflammatory disease
  • Acute cholecystitis
• Pneumonia
• Osteomyelitis – characterized by localized pain, tenderness, and swelling affecting a single site, limited range of motion, and/or prolonged fever and pain.
• Avascular necrosis
• Leg ulcers

When indicated, initiate diagnostic evaluation of causes of pain other than a VOC while beginning to treat pain.

Labs include:

• Complete blood count, which may show:
  • Decreased Hb from baseline
  • Increased RDW from baseline
  • Increased reticulocyte count from baseline
  • Leukocytosis
  • Thrombocytosis or decreased platelet count
• Peripheral smear, showing presence of:
  • Sickle cells
  • Nucleated red cells
  • Howell Jolly bodies
• Hemolytic indices, which may be accentuated from baseline:
  • Low Haptoglobin
  • Elevated LDH
  • Elevated indirect bilirubin
  • Elevated AST

Treatment:

Treat as medical emergency because patients with acute pain crisis are at risk for developing additional complications. 2014 NIH guidelines suggest:

• Pain control:
• The primary management of a VOC:
  • Typically with parenteral opioids.
  • Rapidly initiate analgesic therapy within 30 minutes of triage or within 60 minutes of registration.
  • Around-the-clock opioid administration by patient-controlled analgesia (PCA) or frequently scheduled doses versus “as requested” (PRN) administration.
  • Base analgesic selection on pain assessment, associated symptoms, outpatient analgesic use, patient knowledge of effective agents and doses, and past experience with side effects.
  • In adults and children with a VOC, administer oral NSAIDS as an adjuvant analgesic in the absence of contraindications (e.g., chronic sickle nephropathy or other chronic kidney diseases).

• Incentive spirometry – encourage use of incentive spirometry while awake to reduce the risk of acute chest syndrome.
• Hydration:
  • In euvolemic adults and children with SCD and a VOC who are unable to drink fluids, provide intravenous hydration at no more than maintenance rate to avoid over-hydration.
  • Encourage patients to use water for oral hydration.
• Transfusion – in adults and children with SCD and a VOC, do not administer a blood transfusion unless there are other indications for transfusion.
• Supplemental oxygen – administer oxygen in adults and children with SCD and a VOC with an oxygen saturation <95 percent on room air.

Prognosis

In VOC, pain typically peaks on third day and resolves by 6th or 7th day.

VOC is associated with increased risk of other SCD complications including:

• Acute chest syndrome
• Hepatic and renal involvement
• Cerebrovascular accident
• Multi-organ failure

Acute chest syndrome occurs in 10%–20% of hospitalized patients with SCD, usually manifesting 1-3 days after admission.

Disease modifying treatments that reduce the incidence of further acute pain episodes include:

• Hydroxyurea
• Crizanlizumab
• L-glutamine