# Sickle Cell Crises in the ED

## Introduction

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide, affecting approximately 100,000 individuals in the United States and millions globally. Patients with SCD present to the ED frequently with acute crises that range from painful vaso-occlusive episodes to life-threatening emergencies including acute chest syndrome, stroke, and splenic sequestration. Emergency physicians must provide rapid, evidence-based care while addressing the well-documented disparities in pain management and implicit bias that affect this patient population.

## Pathophysiology

Hemoglobin S results from a single amino acid substitution of glutamic acid to valine at position 6 of the beta-globin chain. Under conditions of hypoxia, dehydration, acidosis, or temperature extremes, HbS polymerizes, causing red blood cells to assume a rigid, sickled shape. Sickled cells cause vaso-occlusion in the microcirculation, producing tissue ischemia and infarction. Chronic hemolysis leads to a baseline anemia with hemoglobin typically between 6 and 9 g/dL, an elevated reticulocyte count, and complications of chronic hemolytic anemia including gallstones and iron overload from transfusions. Endothelial dysfunction and chronic inflammation contribute to vasculopathy, pulmonary hypertension, and organ damage.

## Vaso-Occlusive Crisis (VOC)

### Clinical Presentation

VOC presents with severe pain in bones (long bones, spine, pelvis, ribs), chest, and abdomen. Pain is typically recurrent with a pattern familiar to the patient, and deviation from the baseline pattern should raise concern for alternative diagnoses. Triggers include infection, dehydration, cold exposure, stress, menses, altitude, and alcohol. No reliable laboratory test confirms or excludes VOC; it is a clinical diagnosis.

### Pain Management -- The Priority

Pain should be treated rapidly and aggressively, with a target of analgesic administration within 30 minutes of triage according to NHLBI guidelines. IV opioids are first-line for severe pain: hydromorphone 0.015 mg/kg IV or morphine 0.1 to 0.15 mg/kg IV every 15 to 20 minutes until pain is controlled. The patient's individualized pain plan should be used if one exists, as many SCD patients have established protocols. Meperidine must not be used because normeperidine accumulation causes seizures. Multimodal adjuncts include ketorolac 15 to 30 mg IV, acetaminophen 1 g IV or PO, ibuprofen, and muscle relaxants. Patient-controlled analgesia should be initiated early for admitted patients. Intranasal fentanyl at 2 mcg/kg is an effective option for rapid analgesia before IV access. Under-dosing and under-treatment must be avoided: opioid tolerance is expected and is not the same as addiction, and implicit bias regarding pain management in SCD is well-documented.

### Supportive Care

IV fluid hydration with isotonic crystalloid at maintenance rate is appropriate, but aggressive boluses should be avoided as they can precipitate acute chest syndrome through hemodilution and fluid overload. Incentive spirometry with 10 breaths every 2 hours while awake reduces atelectasis and the risk of acute chest syndrome. Supplemental oxygen should be given only if the patient is hypoxic with SpO2 below 95%; routine oxygen in non-hypoxic patients has not shown benefit and may suppress erythropoiesis.

<image>Pathophysiology diagram of sickle cell vaso-occlusive crisis showing the cascade from HbS polymerization under hypoxic conditions to red cell sickling, microvascular occlusion, tissue ischemia, pain signal generation, and inflammatory mediator release with treatment intervention points marked</image>

## Acute Chest Syndrome (ACS)

### Definition

Acute chest syndrome is defined as a new pulmonary infiltrate on chest X-ray involving at least one complete lung segment, accompanied by at least one of the following: fever greater than 38.5 degrees Celsius, respiratory symptoms (cough, dyspnea, chest pain), or hypoxia.

### Etiology

ACS is multifactorial, resulting from pulmonary fat embolism from bone marrow necrosis, infection (Chlamydia pneumoniae, Mycoplasma, viral), pulmonary infarction from in situ sickling, and hypoventilation or atelectasis. It often evolves from an ongoing VOC, as the combination of VOC and atelectasis from splinting produces ACS.

### Clinical Features

Patients present with chest pain, cough, fever, dyspnea, and hypoxia. ACS may present de novo or develop during a hospitalization for VOC, making close monitoring of all admitted VOC patients essential. Bilateral lower lobe infiltrates are the most common radiographic pattern. The condition can rapidly progress to ARDS, respiratory failure, and death.

### Management

Supplemental oxygen should maintain SpO2 above 95%. Simple or exchange transfusion should target hemoglobin to 10 g/dL, but this level should not be exceeded to avoid hyperviscosity. Exchange transfusion is preferred in severe ACS with PaO2 less than 60 mmHg, rapidly worsening infiltrates, or multilobar disease, as it reduces HbS to less than 30% without increasing viscosity. Antibiotics should cover atypical organisms with azithromycin or a fluoroquinolone plus a cephalosporin such as ceftriaxone. Bronchodilators are indicated for patients with wheezing or a reactive airway component. Incentive spirometry should be continued aggressively, and IV fluids should be maintained at maintenance rate while avoiding excessive volume, as fluid overload worsens ACS.

## Stroke in SCD

Ischemic stroke occurs in 11% of SCD patients by age 20 and involves large vessel vasculopathy of the internal carotid and middle cerebral arteries. Hemorrhagic stroke is more common in adults with SCD. Presentation includes focal neurologic deficits, altered mental status, seizure, and severe headache. Emergency management begins with immediate CT head without contrast followed by CTA. Emergent exchange transfusion to reduce HbS to less than 30% is the definitive treatment and should not be delayed. tPA is generally not recommended due to hemorrhagic stroke risk and the primary vasculopathy mechanism. Neurology and hematology consultation should be obtained.

## Splenic Sequestration

Splenic sequestration involves rapid pooling of blood within the spleen, causing acute and potentially fatal anemia and hypovolemic shock. It is most common in children under 5 years because autosplenic infarction occurs by age 5 in HbSS disease, but it can occur in adults with HbSC or HbS-beta-thalassemia who retain splenic tissue. Patients present with acute left upper quadrant pain, rapidly enlarging spleen, pallor, tachycardia, hypotension, and a hemoglobin drop of 2 g/dL or more below baseline. Treatment consists of emergent simple transfusion, IV fluid resuscitation, and splenectomy for recurrent episodes.

## Aplastic Crisis

Parvovirus B19 infection causes transient red cell aplasia by arresting erythropoiesis for 7 to 10 days. The reticulocyte count is critically low at less than 1% despite severe anemia, which distinguishes aplastic crisis from hemolytic crisis or sequestration. The condition is self-limited but may require transfusion support if hemoglobin drops to dangerously low levels. It is contagious to other SCD patients and pregnant women, and droplet precautions should be implemented.

## Priapism

Priapism is a prolonged, painful erection lasting more than 4 hours due to vaso-occlusion of penile venous drainage. Ischemic or low-flow priapism is a urologic emergency in which corporeal blood is deoxygenated and acidotic. Management involves aspiration of corporal blood via dorsal penile nerve block and large-bore needle, followed by instillation of phenylephrine at 100 to 500 mcg diluted and injected into the corpus cavernosum every 5 minutes. Urology consultation is needed for shunt surgery if the condition is refractory. Tissue damage and erectile dysfunction risk increase significantly after 24 hours.

<image>Diagram showing the major acute complications of sickle cell disease with corresponding body systems: brain (stroke), lungs (acute chest syndrome), spleen (splenic sequestration), bones and joints (vaso-occlusive crisis), kidneys (papillary necrosis), and penis (priapism) with brief management notes for each</image>

| Crisis Type | Pathophysiology | Key Presentation | Distinguishing Feature | Primary Treatment |
|-------------|----------------|------------------|----------------------|-------------------|
| Vaso-occlusive (VOC) | HbS polymerization → microvascular occlusion | Severe bone/chest/abdominal pain | Clinical diagnosis; labs may be normal | Aggressive opioid analgesia + IV fluids |
| Acute chest syndrome | Fat embolism, infection, or in situ sickling in lungs | New infiltrate + fever/hypoxia/respiratory symptoms | Often evolves from VOC admission | Exchange transfusion + antibiotics + O2 |
| Stroke | Large vessel vasculopathy (ICA, MCA) | Focal deficits, AMS, seizure | 11% by age 20; tPA NOT recommended | Emergent exchange transfusion (HbS < 30%) |
| Splenic sequestration | Rapid blood pooling in spleen | LUQ pain, acute anemia, splenomegaly, shock | Hgb drop ≥ 2 g/dL below baseline | Emergent simple transfusion + IV fluids |
| Aplastic crisis | Parvovirus B19 → erythropoiesis arrest | Severe anemia, fatigue | Reticulocyte count < 1% (critically low) | Transfusion support; self-limited |
| Priapism | Vaso-occlusion of penile venous drainage | Painful erection > 4 hours | Low-flow/ischemic type | Aspiration + phenylephrine injection |

## Other ED Presentations

Acute cholecystitis from pigmented gallstones caused by chronic hemolysis is present in 50 to 70% of SCD patients by adulthood. Papillary necrosis from renal medullary ischemia presents with hematuria and flank pain. Osteomyelitis, most commonly caused by Salmonella in SCD and also by Staphylococcus, must be differentiated from bone infarction, which can be challenging. Pulmonary hypertension is a chronic complication whose acute decompensation presents with dyspnea and right heart failure.

## Clinical Pearls

Pain is the most common reason SCD patients present to the ED, and it should be treated rapidly, aggressively, and without judgment; opioid tolerance is expected, and individualized pain plans should be followed. Acute chest syndrome can develop during any VOC admission, making enforcement of incentive spirometry, monitoring for respiratory deterioration, and avoidance of fluid overload essential. Exchange transfusion is the treatment of choice for severe ACS and stroke in SCD, and hemoglobin should not exceed 10 g/dL to avoid hyperviscosity. A low reticulocyte count in a severely anemic SCD patient points to aplastic crisis from parvovirus B19 rather than hemolytic or sequestration crisis. Stroke should always be considered in any SCD patient with new neurologic symptoms, and emergent exchange transfusion, not tPA, is the standard of care.

## References

1. Yawn BP, et al. "Management of Sickle Cell Disease: Summary of the 2014 Evidence-Based Report by Expert Panel Members." *JAMA*. 2014;312(10):1033-1048.
2. Howard J. "Sickle Cell Disease: When and How to Transfuse." *Hematology ASH Education Program*. 2016;2016(1):625-631.
3. Glassberg JA, et al. "Emergency Department Management of Sickle Cell Disease: An Evidence-Based Review." *Annals of Emergency Medicine*. 2013;61(5):S47.
4. Rees DC, et al. "Sickle-Cell Disease." *The Lancet*. 2010;376(9757):2018-2031.