Symptoms of Sickle Cell Disease
Sickle cell disease (SCD) is characterized by acute painful crises, chronic anemia, increased susceptibility to infections, and progressive multi-organ damage that can significantly impact morbidity, mortality, and quality of life. 1, 2
Pathophysiology
Sickle cell disease results from a mutation in the β-globin gene that produces abnormal hemoglobin S (HbS). When deoxygenated, HbS forms polymers that cause red blood cells to:
- Deform into characteristic sickle or crescent shapes
- Become rigid and fragile
- Adhere to vascular endothelium
- Undergo hemolysis
These changes lead to vaso-occlusion, ischemia-reperfusion injury, chronic inflammation, and end-organ damage. 1, 3
Acute Symptoms
Acute Painful Crises
- Location varies by age:
- Infants: Fingers and hands (dactylitis)
- Children and adults: Long bones, sternum, ribs, back 1
- Pain can be severe and debilitating
- Often triggered by dehydration, infection, stress, or extreme temperatures 4
Fever and Infections
- Temperature ≥38°C (≥100.4°F) requires immediate medical attention
- High risk for septicemia and meningitis, particularly with encapsulated bacteria
- Requires urgent evaluation, blood cultures, and prompt administration of broad-spectrum antibiotics 1, 4
Acute Chest Syndrome
- Characterized by:
- New pulmonary infiltrates on chest X-ray
- Fever
- Respiratory symptoms (chest pain, tachypnea, cough, wheeze)
- Decreasing hemoglobin
- Hypoxemia
- Common post-surgical complication
- Potentially life-threatening 1, 4
Other Acute Complications
- Splenic sequestration crisis: Massive splenomegaly, acute anemia, hypovolemic shock (common in children 5 months-2 years) 1
- Aplastic crisis: Temporary cessation of red blood cell production, often triggered by parvovirus B19 infection 1
- Stroke: Requires immediate neuroimaging and exchange transfusion 4
- Priapism: Painful, prolonged erection that may lead to impotence if untreated 1
Chronic Symptoms and Complications
Hematologic
- Chronic hemolytic anemia
- Fatigue
- Exercise intolerance
- Jaundice (yellowing of skin and eyes) 2
Neurological
- Stroke (occurs in up to 10% of children)
- Silent cerebral infarcts (40% of adults)
- Cognitive impairment 1
Cardiorespiratory
- Obstructive sleep apnea
- Chronic lung disease (restrictive pattern in 70%)
- Congestive heart failure
- Pulmonary hypertension (6% of adults) 1
Renal
- Hyposthenuria (inability to concentrate urine) in all patients
- Proteinuria (40% of adults)
- Renal insufficiency (20% of adults) 1
Orthopedic
- Avascular necrosis of the femoral head
- Osteomyelitis 1
Other Chronic Complications
- Cholelithiasis (gallstones)
- Retinopathy
- Leg ulcers
- Erectile dysfunction 1
Symptom Variation by Genotype
The severity of symptoms varies significantly based on SCD genotype:
- HbSS and HbSβ⁰ thalassemia: Most severe forms with frequent symptoms
- HbSC and HbSβ⁺ thalassemia: Generally milder disease with fewer symptoms
- Sickle cell trait (HbAS): Usually asymptomatic under normal conditions 1, 2
Special Considerations
Children
- Hyposplenism develops within first few years of life
- Adenotonsillar hypertrophy may cause obstructive sleep apnea
- Regular transcranial Doppler screening recommended for stroke risk assessment 1
Perioperative Period
- Increased risk for acute chest syndrome
- Vaso-occlusive crisis
- Infection
- Requires meticulous management to avoid dehydration, hypoxia, acidosis, hypothermia, and pain 4
Warning Signs Requiring Immediate Medical Attention
- Fever ≥38°C (≥100.4°F)
- Respiratory symptoms (difficulty breathing, chest pain)
- Severe pain unresponsive to home management
- Neurological symptoms (headache, seizures, weakness)
- Priapism lasting >4 hours
- Sudden vision changes
- Severe abdominal pain 1, 4
Early recognition of these symptoms and prompt medical intervention are critical to reduce morbidity and mortality in patients with sickle cell disease.