What are the diagnostic tests and management strategies for sickle cell disease?

Diagnostic Tests and Management Strategies for Sickle Cell Disease

The diagnosis of sickle cell disease requires a comprehensive hemoglobinopathy screen using high-performance liquid chromatography, capillary electrophoresis, mass spectrometry, or gel electrophoresis, which should be confirmed by a second test such as solubility testing or electrophoresis on agar in citrate buffer. 1, 2

Diagnostic Tests

Primary Diagnostic Methods

• Newborn screening programs can detect sickle cell disease where available 3
• Hemoglobin electrophoresis confirms the presence of hemoglobin S 3
• A positive sickle solubility test should not be used in isolation as it doesn't differentiate between heterozygous, compound heterozygous, or homozygous states 1
• Isoelectrofocusing provides better resolution than conventional cellulose acetate electrophoresis at alkaline pH 2
• Cation exchange HPLC is sometimes used as a first-line test in some laboratories 2
• The HemoTypeSC™ test has shown 100% sensitivity and specificity for detecting hemoglobins A, S, and C in screening settings, but should be followed by confirmatory testing 4

Additional Laboratory Evaluation

• Complete blood count to assess for normocytic normochromic anemia 5, 3
• Reticulocyte count to evaluate bone marrow response to hemolysis 5, 3
• Markers of hemolysis including bilirubin (total and direct) 5
• Renal function tests (BUN, creatinine) to evaluate for kidney injury 5
• Liver function tests (AST, ALT, alkaline phosphatase) to assess hepatobiliary involvement 5
• Coagulation studies (PT, PTT) to evaluate for coagulopathy 5
• Urinalysis to check for hematuria, proteinuria, or signs of urinary tract infection 5

Specialized Testing Based on Clinical Presentation

• Arterial blood gas for patients with suspected acute chest syndrome 5
• Blood cultures if infection is suspected 5
• Transcranial Doppler studies for children to assess stroke risk 1, 5
• Echocardiography for patients with signs or symptoms suggestive of pulmonary hypertension 1
• Pulmonary function testing for patients with respiratory symptoms 1
• Sleep studies for patients with symptoms of sleep-disordered breathing 1

Management Strategies

Disease-Modifying Therapies

• Hydroxyurea is the first-line disease-modifying therapy for most individuals with SCD, as it increases fetal hemoglobin and reduces red blood cell sickling 6
• L-glutamine, crizanlizumab, and voxelotor are approved as adjunctive or second-line agents 6
• Hematopoietic stem cell transplant is the only curative therapy, with best results seen in children with a matched sibling donor 6

Acute Complications Management

• Pain management with analgesics, adequate hydration, and in severe cases, parenteral opioids 3
• Blood transfusions to improve oxygen delivery during acute complications 7
• Prompt treatment of infections due to increased susceptibility from splenic dysfunction 3
• Specific management for acute chest syndrome, including oxygen therapy, antibiotics, and possibly exchange transfusion 1
• Management of stroke with immediate neurological evaluation and appropriate interventions 3
• Treatment of priapism, which can occur in children and adolescents 3

Chronic Complications Management

• Regular screening with transcranial Doppler for children to assess stroke risk 1
• Echocardiography for patients with signs or symptoms of pulmonary hypertension 1
• Combination therapy with hydroxyurea and erythropoiesis-stimulating agents for worsening anemia associated with chronic kidney disease 1
• Indefinite anticoagulation for adults with first unprovoked VTE or recurrent provoked VTE 1
• Defined periods of anticoagulation (3-6 months) for adults with first surgically or nonsurgically provoked VTE 1

Important Clinical Considerations

• Baseline laboratory values should be known for comparison, as many patients with SCD have chronic abnormalities 5
• Laboratory abnormalities should be interpreted in the context of the patient's clinical presentation 5
• Avoid relying solely on hemoglobin levels to determine the need for transfusion - consider the patient's baseline hemoglobin and clinical status 5
• Monitor for complications of treatment, such as fluid overload or transfusion reactions 5
• Clearly communicate the diagnosis of SCD on laboratory request forms to ensure appropriate processing and interpretation 5

Common Pitfalls in Diagnosis and Management

• Using sickle solubility test alone for diagnosis, which can give false negative results in neonates or heavily transfused patients 1
• Failing to confirm positive screening tests with a second, more specific test 2
• Not evaluating other factors that interact with HbS, such as HbF level, sickle cell restriction haplotype, and association with alpha-thalassemias 2
• Overlooking the transition from pediatric to adult-focused healthcare, which is associated with higher mortality 6
• Underestimating the risk of pain medication addiction, which is not higher in SCD patients than in the general population 6