Sickle Cell Disease (SCD) is a group of inherited hemoglobinopathies characterized by the presence of hemoglobin S (HbS) resulting from a point mutation in the β-globin gene (Glu6Val). Under deoxygenated conditions, HbS polymerizes, leading to red blood cell (RBC) deformation, chronic hemolysis, vaso-occlusion, and progressive organ damage.

The most severe genotype is sickle cell anemia (SCA, HbSS), in which an individual inherits two HbS alleles (homozygous state). Other clinically significant genotypes include HbSC and HbS/β-thalassemia.

SCD is inherited in an autosomal recessive pattern and manifests clinically after 6 months of age due to the decline in fetal hemoglobin (HbF).

Risk Factors

• Inheritance of HbS gene (parental carrier state)

• African, Middle Eastern, Mediterranean, and Indian ancestry

• Dehydration

• Infection

• Hypoxia

• Acidosis

• Cold exposure

• High altitude

• Surgery or anesthesia

• Pregnancy

Pathophysiology (Essential for Professional Reference)

• HbS polymerization under low oxygen tension

• RBC sickling → decreased deformability

• Vaso-occlusion → ischemia and infarction

• Chronic hemolysis → anemia, hyperbilirubinemia

• Nitric oxide depletion → endothelial dysfunction

• Functional asplenia → immunocompromise

Signs and Symptoms

Clinical manifestations are variable and may include:

• Chronic anemia

• Jaundice

• Recurrent pain episodes

• Growth delay (children)

• Hepatosplenomegaly (early childhood)

• Leg ulcers (adults)

• Priapism

• Gallstones

Symptoms begin after 6 months of age and typically occur as crises.

Types of Crisis in SCD

1. Vaso-Occlusive Crisis (VOC)

• Most common

• Severe pain (back, limbs, abdomen, chest)

• Triggered by dehydration, infection, stress

• Diagnosis of exclusion (rule out osteomyelitis, appendicitis, etc.)

2. Hemolytic Crisis

• Sudden increase in hemolysis

• Jaundice

• Dark urine

• Falling hemoglobin

3. Sequestration Crisis

• Sudden splenic or hepatic enlargement

• Rapid fall in hematocrit

• Hypovolemic shock (especially in children)

4. Aplastic Crisis

• Bone marrow suppression (often Parvovirus B19)

• Severe anemia

• Reticulocytopenia

Medical Emergencies in SCD

Acute Chest Syndrome (ACS)

• Chest pain

• Fever

• Hypoxia

• Pulmonary infiltrates on chest X-ray

• Leading cause of mortality

Stroke

• Headache

• Focal neurological deficit

• Requires urgent exchange transfusion

Splenic Sequestration

• Rapid splenic enlargement

• Pallor

• Hypotension

Severe Infection

• Due to functional asplenia

• Encapsulated organisms (e.g., Streptococcus pneumoniae)

Diagnostic Criteria

Diagnosis requires demonstration of HbS:

• Hemoglobin electrophoresis (gold standard)

• High-performance liquid chromatography (HPLC)

• Isoelectric focusing (IEF)

Newborn screening programs are recommended where available.

Investigations

Screening Tests

• Sickling test

• Sickle solubility test

Confirmatory Tests

• Hemoglobin electrophoresis

• HPLC

• IEF

• Sickle scan

Laboratory Monitoring

• Full blood count (FBC)

• Reticulocyte count (typically 5–15%)

• Peripheral smear:

  • Sickled cells

  • Howell-Jolly bodies

  • Target cells

  • Polychromasia

• LDH ↑

• Indirect bilirubin ↑

• Haptoglobin ↓

• AST mildly ↑

Organ Monitoring

• Urinalysis (proteinuria)

• Transcranial Doppler (age 2–16 years)

• Echocardiography (pulmonary hypertension)

• Ophthalmologic screening

• Renal function tests

Treatment

Non-Pharmacological Management

• Adequate hydration

• Avoid temperature extremes

• Oxygen therapy (if hypoxic)

• Prompt infection treatment

• Nutritional support

• Genetic counseling

• Psychosocial support

Pharmacological Management

1. Infection Prophylaxis

Penicillin prophylaxis

• <3 years: 125 mg PO twice daily

• ≥3 years: 250 mg PO twice daily

• Continue until 5 years (or longer in high-risk cases)

2. Immunization

• PCV-13 (2, 4, 6 months + booster at 12–15 months)

• PPSV-23 at 2 years; repeat every 5 years

• Annual influenza vaccine

• Meningococcal vaccine

• Hepatitis B vaccine

Pain Management

Mild Pain

• Paracetamol (15 mg/kg children; 1 g adults)

Moderate Pain

• Add Ibuprofen (5 mg/kg children; 400 mg adults)

Severe Pain

• Oral morphine:

  • Child: 0.5 mg/kg every 3–4 hours

  • Adult: 5–10 mg every 3–4 hours

Hydration Protocol

<10 kg → 150 mL/kg/day11–20 kg → 1500 mL + 75 mL/kg for each kg above 10

Divide total by 24 to calculate hourly rate.

Hydroxyurea Therapy

Hydroxyurea increases HbF, reduces VOC frequency, ACS, and mortality.

Indications

• ≥3 severe VOC/year

• ≥2 ACS episodes

• Chronic symptomatic anemia

• Recurrent priapism

• Alternative to chronic transfusion for stroke prevention

• CKD with erythropoietin therapy

Dosage

• Adults: 15 mg/kg/day

• Children: 20 mg/kg/day

• CKD: 5–10 mg/kg/day

Monitoring

• Weekly CBC (first 4 weeks)

• Fortnightly (next 8 weeks)

• Monthly thereafter

• Target ANC >2000/µL

• Platelets >80,000/µL

Hold if neutropenia or thrombocytopenia occurs.

Contraindications

• Pregnancy

• Breastfeeding

• Discontinue 3 months before conception

Blood Transfusion in SCD

Simple transfusion

• Severe anemia

• Aplastic crisis

Exchange transfusion

• Stroke

• Acute chest syndrome

• Multi-organ failure

• Preoperative management

• Target HbS <30%

Prevention

• Newborn screening

• Genetic counseling

• Carrier screening

• Routine vaccinations

• Stroke screening (TCD)

• Renal and ophthalmologic screening

• Early hydroxyurea initiation

• Education on hydration and infection prevention

Complications

• Stroke

• Pulmonary hypertension

• Chronic kidney disease

• Avascular necrosis

• Leg ulcers

• Retinopathy

• Gallstones

• Iron overload (transfusion-related)

Prognosis

With comprehensive care (vaccination, hydroxyurea, stroke prevention), life expectancy has significantly improved into adulthood. However, morbidity remains high without appropriate management.