Overview
Definition:
Sickle cell disease (SCD) is a group of inherited red blood cell disorders characterized by an abnormality in the oxygen-carrying protein hemoglobin
The most common type is sickle cell anemia (SCA), caused by homozygous inheritance of the sickle cell gene (HbSS)
Red blood cells become sickle-shaped or crescent-shaped when they are exposed to low oxygen levels
These sickle cells are rigid and sticky, and can block blood flow, leading to pain, organ damage, and other serious complications.
Epidemiology:
SCD is one of the most common inherited blood disorders worldwide
In India, it is prevalent in certain tribal populations and southern states like Tamil Nadu, Odisha, and Gujarat, with carrier rates varying significantly by region
The estimated incidence varies, but is significant in endemic areas
It is a major cause of morbidity and mortality in affected children.
Clinical Significance:
SCD has a profound impact on a child's health and quality of life
Stroke is a devastating complication, with a significant risk of first and recurrent strokes in children with SCD
Effective stroke prevention strategies, particularly the judicious use of hydroxyurea, are critical for improving long-term outcomes and reducing mortality
Understanding these management principles is vital for pediatric residents preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Children with SCD typically present in infancy or early childhood with symptoms related to vaso-occlusive crises
These include severe pain in bones, chest, abdomen, and joints
Other common symptoms are pallor due to anemia, jaundice, fever, and delayed growth and puberty
Neurological symptoms heralding a stroke include sudden onset of weakness or numbness, difficulty speaking, vision changes, headache, and seizures.
Signs:
Physical examination may reveal pallor, jaundice, splenomegaly (in younger children, becoming fibrotic with age), cardiomegaly, murmurs, and signs of chronic organ damage
Neurological deficits such as focal weakness, cranial nerve palsies, or altered mental status are suggestive of stroke.
Diagnostic Criteria:
Diagnosis is confirmed by hemoglobin electrophoresis, which identifies the presence of hemoglobin S (HbS)
For SCA (HbSS), electrophoresis shows HbS and no or minimal HbA
Genotyping can also be used
Stroke is diagnosed based on clinical presentation and confirmed by neuroimaging (CT scan or MRI) showing evidence of infarction.
Diagnostic Approach
History Taking:
A detailed birth history, family history of anemia or blood disorders, and a history of recurrent painful episodes, fever, jaundice, or prior stroke/TIA are crucial
Inquire about any recent illnesses or triggers for crises
Ask about vaccination status and prior medical interventions.
Physical Examination:
A thorough systemic examination focusing on signs of anemia (pallor), jaundice, hepatosplenomegaly, cardiac function, neurological deficits, and skin findings (e.g., leg ulcers in older children) is essential
Assess growth parameters and pubertal development.
Investigations:
Complete blood count (CBC) typically shows chronic hemolytic anemia (Hb 6-10 g/dL), elevated reticulocyte count, and sometimes leukocytosis
Peripheral smear reveals sickle-shaped red blood cells, target cells, and Howell-Jolly bodies
Hemoglobin electrophoresis is the gold standard for diagnosis, showing HbS
Transcranial Doppler (TCD) ultrasound is used for stroke risk stratification in children aged 2-16 years with HbSS, identifying those at increased risk of overt stroke.
Differential Diagnosis:
Other causes of hemolytic anemia (e.g., G6PD deficiency, thalassemia trait), other hemoglobinopathies (e.g., HbSC disease, sickle-beta thalassemia), and conditions mimicking painful crises (e.g., osteomyelitis, appendicitis) should be considered
Differentiating TIA from overt stroke requires careful neuroimaging.
Management
Initial Management:
Management of acute sickle cell crises involves aggressive hydration with intravenous fluids, pain management with analgesics (opioids may be required), and prompt treatment of any precipitating factors like infection
Oxygen supplementation may be needed if hypoxic
Transfusion therapy (exchange transfusion or simple transfusion) may be indicated for severe anemia, acute chest syndrome, or stroke.
Medical Management:
Hydroxyurea is the cornerstone of chronic management for SCD, particularly for children with recurrent vaso-occlusive crises and those identified as high risk for stroke
It increases fetal hemoglobin (HbF) levels, which inhibits HbS polymerization
The typical starting dose in children is 15-20 mg/kg/day, titrated to a maximum of 35 mg/kg/day or until hematologic toxicity (neutropenia, anemia, thrombocytopenia)
Regular monitoring of CBC, liver function tests, and renal function is essential
Prophylactic penicillin is recommended for infants and young children to prevent pneumococcal sepsis
Pneumococcal and other relevant vaccinations are crucial.
Stroke Prevention:
For children aged 2-16 years with HbSS and abnormal TCD velocities (>= 200 cm/s), chronic blood transfusions are indicated to prevent overt stroke
For those with very high risk or who cannot tolerate transfusions, hydroxyurea is also employed to reduce stroke risk, often used in conjunction with transfusions
For children with overt stroke, aggressive management including transfusion therapy and rehabilitation is paramount.
Supportive Care:
Comprehensive care involves regular monitoring for complications, prompt management of infections, nutritional support, genetic counseling, and psychosocial support for the child and family
Education on hydration, avoiding triggers, and recognizing early signs of complications is vital.
Complications
Early Complications:
Vaso-occlusive crises (painful episodes), acute chest syndrome, splenic sequestration, avascular necrosis, priapism, and stroke are common early complications
Sepsis is a major threat, especially in young children.
Late Complications:
Chronic organ damage can affect the kidneys (glomerulopathy, renal failure), lungs (pulmonary hypertension), heart (cardiomyopathy), eyes (retinopathy), liver, and skin (leg ulcers)
Delayed puberty, gallstones, and increased susceptibility to infections are also seen.
Prevention Strategies:
Primary stroke prevention is achieved through regular TCD screening in children aged 2-16 years and initiating prophylactic transfusion therapy or hydroxyurea in high-risk individuals
Secondary stroke prevention involves continued aggressive management, often with chronic transfusions and hydroxyurea
Prompt recognition and treatment of infections with antibiotics and vaccinations significantly reduce the risk of sepsis
Maintaining adequate hydration and avoiding triggers for crises helps prevent vaso-occlusive events.
Prognosis
Factors Affecting Prognosis:
The prognosis for SCD has improved significantly with advances in management
Factors influencing prognosis include genotype (HbSS generally has a poorer prognosis than HbSC or sickle-beta thalassemia), frequency and severity of vaso-occlusive crises, development of chronic organ damage, and timely access to comprehensive care
Stroke is a major determinant of long-term morbidity and mortality.
Outcomes:
With effective stroke prevention strategies, including TCD screening and hydroxyurea therapy, the incidence of first strokes has decreased
However, recurrent strokes remain a concern
Long-term survival is significantly impacted by the presence and progression of organ damage
Hydroxyurea has been shown to reduce the frequency of painful crises, acute chest syndrome, and the need for transfusions, improving quality of life and potentially survival.
Follow Up:
Children with SCD require lifelong, multidisciplinary follow-up
This includes regular hematology visits, monitoring of organ function (renal, hepatic, cardiac), ophthalmic evaluations, TCD screenings as per guidelines, dental care, and psychological support
Adherence to hydroxyurea therapy and vaccination schedules is critical.
Key Points
Exam Focus:
Understand the pathophysiology of HbS polymerization and its vaso-occlusive consequences
Memorize the indications for hydroxyurea and its mechanism of action (increasing HbF)
Know the TCD screening guidelines and stroke risk stratification in pediatric SCD
Recognize the importance of prompt management of acute crises and infections.
Clinical Pearls:
Always consider SCD in a child presenting with unexplained fever, pain crisis, or anemia, especially in endemic regions
Early initiation of hydroxyurea can significantly alter the disease course
Treat all febrile episodes in young children with SCD as a potential sepsis emergency
Regular TCD screening is a critical preventive measure for stroke in at-risk children.
Common Mistakes:
Underestimating the risk of stroke in asymptomatic children with SCD
Delaying the initiation of hydroxyurea when indicated
Inadequate management of painful crises, leading to undertreatment
Failing to adhere to vaccination protocols
Not performing regular TCD screenings in appropriate age groups
Misinterpreting lab values related to hydroxyurea toxicity.