What are the most common causes of syncope in patients with sickle cell disease?

Most Common Causes of Syncope in Sickle Cell Disease Patients

In patients with sickle cell disease, syncope is most commonly caused by acute vaso-occlusive crises affecting cardiac output, acute chest syndrome compromising pulmonary function, severe anemia from hemolytic or sequestration crises, and arrhythmias secondary to chronic cardiac complications.

Primary Mechanisms of Syncope in SCD

Vaso-Occlusive Phenomena

• Vaso-occlusive crises are responsible for more than 90% of hospitalizations in SCD patients and can precipitate syncope through multiple mechanisms 1, 2.
• The sickling process causes extensive polymerization of hemoglobin S when deoxygenated, leading to red blood cell deformation, vascular occlusion, and end-organ ischemia that can critically reduce cardiac output 3.
• Syncope during vaso-occlusive episodes may result from severe pain-induced vasovagal responses, acute reduction in effective circulating volume, or direct cardiac involvement 3, 4.

Acute Chest Syndrome

• Acute chest syndrome is the most common cause of intensive care admission and death in adult SCD patients, making it a critical consideration when evaluating syncope 2.
• This complication presents with new pulmonary infiltrates and respiratory symptoms, which can rapidly compromise oxygenation and cardiac output sufficient to cause syncope 5, 4.
• The American College of Cardiology specifically recommends excluding acute chest syndrome in SCD patients presenting with chest pain or syncope 4.

Severe Anemia

• Acute worsening of chronic hemolytic anemia can precipitate syncope through inadequate oxygen delivery to the brain 1, 2.
• Splenic sequestration crisis causes rapid spleen enlargement with blood trapping, leading to a hemoglobin drop >2 g/dL and potentially hypovolemic shock 4, 2.
• Transient aplastic crisis (often triggered by parvovirus B19) causes acute exacerbation of anemia with decreased reticulocyte production 3, 4.

Cardiac Complications Leading to Syncope

Structural Heart Disease

• Nearly 80% of SCD patients have cardiac enlargement and murmurs, establishing a substrate for syncope 6.
• Progressive multi-organ damage includes pulmonary hypertension, which is specifically mentioned as a chronic complication requiring evaluation in patients with syncope history 5, 3.
• The 2019 ASH guidelines explicitly list "history of syncope or presyncope" as an indication for pulmonary function testing and cardiac evaluation in SCD patients 5.

Arrhythmias

• Chronic hemolysis causes nitric oxide depletion and vascular endothelial damage, creating a milieu for arrhythmias 3.
• While general syncope guidelines identify arrhythmias as the most common cardiac cause of syncope, SCD patients have additional risk from chronic vasculopathy and decreased functional reserve 5, 7.

Critical Pitfalls to Avoid

Do Not Dismiss Patient Reports

• The diagnosis of acute complications in SCD is based entirely on patient self-report without requiring specific laboratory abnormalities 4.
• Patients with SCD and their caregivers often know their disease best, and their report of typical symptoms should be trusted and acted upon promptly 4.

Recognize Multi-Organ Involvement

• A single presentation may include multiple complications: worsening anemia, vascular events (stroke, thrombosis), acute chest syndrome, or organ sequestration 1.
• Syncope in SCD is frequently superimposed over chronic vasculopathy, immune dysregulation, and decreased functional reserve rather than being an isolated event 7.

Age-Related Considerations

• Splenic sequestration is most common in children and can rapidly lead to hypovolemic shock 2.
• Stroke risk is elevated across all ages in SCD, presenting with hemiparesis, aphasia, seizures, or altered consciousness that may be confused with syncope 3.

Evaluation Algorithm

When evaluating syncope in SCD patients, prioritize:

1. Immediate assessment for acute chest syndrome: Check for chest pain, respiratory symptoms, and obtain chest radiograph 5, 4.
2. Evaluate for severe anemia: Measure hemoglobin and compare to baseline; a drop >2 g/dL suggests sequestration crisis 4.
3. Assess for vaso-occlusive crisis: Trust patient report of typical pain patterns and initiate rapid analgesia 4.
4. Screen for cardiac complications: Given the high prevalence of cardiac involvement and pulmonary hypertension in SCD, ECG and cardiac evaluation are warranted 5, 6.
5. Consider stroke: Evaluate for focal neurological deficits, as stroke is a life-threatening complication in SCD 3, 2.

The pathophysiology of syncope in SCD differs fundamentally from general populations because end-organ ischemia from sickling is superimposed on chronic multi-organ damage, making these patients particularly vulnerable to acute decompensation 7.