What are the initial laboratory tests and management strategies for patients suspected of having sickle cell disease?

Initial Laboratory Tests and Management Strategies for Suspected Sickle Cell Disease

For patients suspected of having sickle cell disease, a full haemoglobinopathy screen using high performance liquid chromatography (HPLC), capillary electrophoresis, mass spectrometry, or gel electrophoresis should be performed as the initial diagnostic test. 1

Diagnostic Laboratory Testing Algorithm

Step 1: Initial Screening Tests

• Complete Blood Count (CBC) - To evaluate baseline hemoglobin levels, red cell indices, and identify elevated white blood cell counts
• Reticulocyte count - To assess bone marrow response and evaluate anemia
• Peripheral blood smear - To identify sickled red blood cells and other morphological abnormalities

Step 2: Hemoglobin Analysis

• Full haemoglobinopathy screen using one of the following methods:
  • High performance liquid chromatography (HPLC)
  • Capillary electrophoresis
  • Mass spectrometry
  • Gel electrophoresis

Step 3: Confirmatory Testing

• A positive screening test should always be confirmed with a second test to ensure accuracy 1
• Confirmatory methods include:
  • Sickle solubility test
  • Electrophoresis on agar in citrate buffer

Important Diagnostic Considerations

1. Avoid using sickle solubility test alone as it:

   • Cannot differentiate between heterozygous, compound heterozygous, or homozygous states
   • May give false negative results in neonates or heavily transfused patients 1

2. Ethnic considerations for screening:

   • All patients should be considered for screening unless they are ethnically of solely northern or eastern European, Jewish, or South-East Asian heritage, or have been screened previously 1
   • Highest prevalence is in individuals of African, Mediterranean, Middle Eastern, and South Asian descent 2

3. Potential pitfalls in diagnosis:

   • False negative results can occur in:
     • Neonates (due to high HbF levels)
     • Recently transfused patients
   • Repeated unnecessary screening should be avoided 1

Management Strategies After Diagnosis

Immediate Management Steps

1. Baseline laboratory evaluations:

   • Comprehensive metabolic panel
   • Liver function tests
   • Renal function tests
   • Iron studies (serum ferritin, transferrin saturation)

2. Screening for complications:

   • Echocardiography to assess for pulmonary hypertension in patients with signs/symptoms 1
   • Transcranial Doppler for children and young people under 17 years to assess stroke risk 1

Ongoing Monitoring

1. Regular follow-up every 3-6 months based on disease severity and complications
2. Monitor for organ damage including:
   • Cardiac function
   • Renal function
   • Pulmonary function in symptomatic patients

Genotype-Specific Considerations

• Different genotypes (HbSS vs. HbSC) may present with varying clinical and laboratory features:
  • HbSS patients typically exhibit more prominent anemia, hemolysis, leukocytosis, and inflammation
  • HbSC patients may have milder clinical manifestations but still require monitoring 3

Prevention of Complications

1. Hydration - Maintain adequate fluid intake
2. Infection prevention - Appropriate vaccinations and prompt treatment of infections
3. Pain management protocols - Develop individualized pain management plans
4. Education about warning signs requiring urgent medical attention:
   • Fever
   • Acute chest syndrome symptoms
   • Stroke symptoms
   • Splenic sequestration
   • Priapism

By following this systematic approach to diagnosis and management, clinicians can ensure timely identification and appropriate care for patients with sickle cell disease, significantly improving morbidity, mortality, and quality of life outcomes.