Overview
Definition:
Sickle cell disease (SCD) is a group of inherited red blood cell disorders characterized by abnormal hemoglobin (HbS)
This leads to chronic hemolytic anemia, vaso-occlusion, and organ damage
Health maintenance focuses on preventing serious complications like stroke and infection.
Epidemiology:
SCD is the most common inherited blood disorder globally, with higher prevalence in individuals of African, Mediterranean, Middle Eastern, and Indian descent
In India, sickle cell disease is prevalent in tribal populations and certain endemic regions, with varying genotypes and severity.
Clinical Significance:
Effective health maintenance in SCD significantly reduces morbidity and mortality
Early identification and consistent management of risks, particularly stroke and overwhelming post-splenectomy infection (OPSI), are crucial for improving long-term outcomes and quality of life for affected children.
Clinical Presentation
Symptoms:
Chronic anemia presenting as pallor and fatigue
Recurrent painful crises (vaso-occlusive crises)
Increased susceptibility to infections, especially pneumococcal
Delayed growth and puberty
Organ-specific symptoms like acute chest syndrome, stroke, priapism, or splenic sequestration.
Signs:
Pallor, jaundice
Splenomegaly (early in life, often shrinks later)
Hepatomegaly
Cardiac murmurs due to anemia
Signs of stroke (focal neurological deficits)
Signs of infection (fever, respiratory distress).
Diagnostic Criteria:
Diagnosis is typically made by newborn screening or laboratory evaluation
Hemoglobin electrophoresis is the gold standard for identifying HbS and other hemoglobin variants
Complete blood count (CBC) reveals anemia, reticulocytosis, and characteristic sickle-shaped red blood cells on peripheral smear.
Diagnostic Approach
History Taking:
Detailed family history of anemia or blood disorders
History of painful episodes, fevers, and previous hospitalizations
Previous infections, blood transfusions, or stroke
Current medications and adherence to prophylaxis
Immunization status.
Physical Examination:
Thorough physical examination focusing on signs of anemia, jaundice, organomegaly (spleen, liver), cardiovascular system, neurological assessment for focal deficits, and assessment of skin integrity to identify potential infection sites.
Investigations:
Hemoglobin electrophoresis: Confirms diagnosis and genotype (HbSS, HbSC, HbS-beta-thalassemia)
Complete blood count (CBC): Monitors anemia, reticulocyte count, and white blood cell count
Renal and liver function tests: Assess organ function
Urine analysis: Detects proteinuria and hematuria
Echocardiogram: Evaluates cardiac function and pulmonary hypertension
Imaging studies (MRI/CT): For suspected stroke or organ damage.
Differential Diagnosis:
Other hemoglobinopathies (thalassemias, HbC disease)
Autoimmune hemolytic anemia
Sepsis with anemia
Other causes of painful crises (e.g., osteomyelitis)
Hereditary spherocytosis.
Management
Initial Management:
For vaso-occlusive crisis: hydration, analgesia (opioids), oxygen if hypoxic, and treatment of precipitating factors (e.g., infection)
For fever: aggressive evaluation for infection, prompt broad-spectrum antibiotics
For acute chest syndrome: oxygen, antibiotics, pain control, consideration for exchange transfusion.
Medical Management:
Penicillin prophylaxis: Recommended from 2 months of age until at least 5 years, or longer based on clinical assessment and splenic function
Doses: typically 125 mg BID for <3 years, 250 mg BID for >3 years
Hydroxyurea: Increases fetal hemoglobin (HbF), reducing pain crises and acute chest syndrome
Monitor CBC, liver/renal function
Regular blood transfusions: For severe anemia, stroke, or recurrent acute chest syndrome
Exchange transfusion may be used for stroke or severe acute chest syndrome
Pain management: NSAIDs, opioids (morphine, hydromorphone), patient-controlled analgesia (PCA).
Supportive Care:
Nutritional support: Adequate caloric and fluid intake
Genetic counseling for families
Psychosocial support for patients and families
Multidisciplinary care team including hematologist, pediatrician, social worker, and child life specialist
Pain management strategies beyond pharmacotherapy: distraction, relaxation techniques
Patient education regarding hydration, fever, and when to seek medical attention.
Prevention Strategies:
Vaccinations: Pneumococcal conjugate vaccine (PCV13), pneumococcal polysaccharide vaccine (PPSV23), Haemophilus influenzae type b (Hib), meningococcal conjugate vaccine
Annual influenza vaccination
Regular dental check-ups
Avoidance of dehydration and extreme temperatures
Prompt recognition and treatment of fever.
Transcranial Doppler Screening
Purpose:
Transcranial Doppler (TCD) ultrasonography is a non-invasive test used to assess the velocity of blood flow in the intracranial arteries
It identifies children with sickle cell disease who are at increased risk of stroke.
Indications:
Recommended for all children with sickle cell anemia (HbSS) and sickle cell-beta(0)-thalassemia between the ages of 2 and 16 years, typically starting at age 2
TCD screening is also considered for other genotypes with high stroke risk.
Interpretation:
Abnormal TCD results are defined by specific blood flow velocities, typically > 200 cm/s in the middle cerebral artery (MCA) or internal carotid artery (ICA), or > 170 cm/s in the anterior cerebral artery (ACA)
Time-averaged mean velocity (TAMV) is used for standardized interpretation
Conditional and abnormal TCD findings indicate increased stroke risk.
Management Of Abnormal Tcd:
Children with abnormal TCD velocities are at high risk for ischemic stroke and should be considered for chronic blood transfusion therapy
Transfusion is typically initiated with monthly packed red blood cell transfusions to maintain hemoglobin S levels below 30%
Regular TCD follow-up is performed to monitor the effectiveness of transfusions and assess for normalization of velocities.
Follow Up Screening:
Children with normal TCD velocities should be rescreened annually until age 16
Children with conditional TCD velocities should be rescreened every 6 months and may benefit from close monitoring and lifestyle modifications
Children with abnormal velocities receive chronic transfusions and are monitored with TCD every 3-6 months.
Complications
Early Complications:
Vaso-occlusive crises (painful episodes)
Acute chest syndrome
Stroke (ischemic or hemorrhagic)
Splenic sequestration
Priapism
Aplastic crisis.
Late Complications:
Chronic organ damage: kidney disease (renal insufficiency, proteinuria), liver disease, pulmonary hypertension, cardiomyopathy
Leg ulcers
Osteomyelitis
Cholelithiasis
Retinopathy
Avascular necrosis of bones
Cognitive impairment.
Prevention Strategies:
Consistent adherence to penicillin prophylaxis and immunizations is paramount for infection prevention
Regular TCD screening and timely initiation of transfusions for stroke risk reduction
Prompt management of painful crises and acute chest syndrome
Use of hydroxyurea to reduce disease severity
Genetic counseling and family support.
Prognosis
Factors Affecting Prognosis:
Genotype (HbSS generally has worse prognosis than HbSC or HbS-beta-thalassemia trait)
Presence and severity of complications (stroke, organ damage)
Adherence to medical management and prophylaxis
Access to comprehensive care and timely interventions.
Outcomes:
With aggressive health maintenance, including penicillin prophylaxis, TCD screening, hydroxyurea, and judicious use of transfusions, the long-term outlook for children with sickle cell disease has significantly improved
Lifespan has increased considerably.
Follow Up:
Lifelong follow-up with a hematologist is essential
Regular monitoring includes CBC, blood chemistries, urinalysis, and organ-specific assessments (e.g., echocardiography, renal function tests, ophthalmology exams)
TCD screening continues until age 16 for most children, with ongoing risk assessment.
Key Points
Exam Focus:
Understand the rationale and schedule for penicillin prophylaxis and TCD screening in children with sickle cell disease
Recognize indications for hydroxyurea and blood transfusions
Identify signs and management of acute complications like vaso-occlusive crisis and acute chest syndrome.
Clinical Pearls:
Always start penicillin prophylaxis by 2 months of age
TCD screening is crucial for primary stroke prevention from age 2
Fever in a child with sickle cell disease is a medical emergency requiring prompt evaluation and broad-spectrum antibiotics
Hydroxyurea is a cornerstone of chronic management for reducing disease burden.
Common Mistakes:
Discontinuation of penicillin prophylaxis too early without adequate clinical assessment
Delaying evaluation and treatment of fever
Not performing or acting upon abnormal TCD findings
Underestimating the pain severity in vaso-occlusive crises
Inconsistent medication adherence by patients or caregivers.