What laboratory studies should be obtained to evaluate a suspected sickle‑cell disease flare (vaso‑occlusive crisis or acute chest syndrome)?

Laboratory Evaluation for Sickle Cell Disease Flare

Obtain a comprehensive laboratory panel including complete blood count, reticulocyte count, markers of hemolysis (total and direct bilirubin), renal function tests (BUN, creatinine), liver function tests (AST, ALT, alkaline phosphatase), electrolytes, coagulation studies (PT, PTT), and urinalysis to assess crisis severity and detect organ damage. 1

Essential Initial Laboratory Tests

Hematologic Assessment

• Complete blood count to evaluate hemoglobin level against the patient's known baseline (typically 6-9 g/dL in HbSS patients), as acute drops indicate hemolysis severity 1, 2
• White blood cell count to identify infection or inflammation, which is commonly elevated during acute crisis 1
• Reticulocyte count to assess bone marrow response to hemolysis, though this reflects chronic hemolysis rather than acute crisis severity 1, 2
• Platelet count as part of the complete blood count to evaluate for thrombocytopenia or thrombocytosis 1

Hemolysis Markers

• Total and direct bilirubin levels, which increase due to red blood cell breakdown during crisis 1, 2
• Interpret reticulocyte count alongside hemoglobin and bilirubin—an inappropriately low reticulocyte count with worsening anemia warrants investigation for parvovirus B19 infection or marrow suppression 2

Organ Function Assessment

• BUN and creatinine to detect acute kidney injury from vaso-occlusion 1, 2
• AST and ALT to identify liver involvement from sickling or hepatic sequestration 1, 2
• Alkaline phosphatase to assess for hepatobiliary complications 1, 2
• Electrolytes to detect imbalances from renal dysfunction or dehydration 1

Coagulation and Infection Screening

• PT and PTT to evaluate for coagulopathy, which can complicate severe crises 1, 2
• Urinalysis to check for hematuria, proteinuria, or urinary tract infection 1, 2
• Blood cultures if fever ≥38.0°C is present, as bacteremia occurs in 3.5% of episodes (14% in infants, 1.8% in patients >10 years) 3

Specialized Tests Based on Clinical Presentation

For Suspected Acute Chest Syndrome

• Arterial blood gas to evaluate oxygenation and acid-base status, as severe hypoxia occurs in 18% of adults and cannot be predicted by examination alone 1, 3
• Chest radiograph to identify new pulmonary infiltrates, which define acute chest syndrome when combined with fever, cough, chest pain, or hypoxemia 4, 3
• Repeat chest X-ray if clinical deterioration occurs even with initial normal imaging, as acute chest syndrome can develop 24 hours after presentation with vaso-occlusive crisis 5

For Suspected Stroke (Especially in Children)

• Review previous transcranial Doppler results from within 12 months (or 24 months for HbSC/HbSβ+ thalassemia) 1, 2

For Priapism Evaluation

• Corporal blood gas to differentiate ischemic from non-ischemic priapism 1

Critical Interpretation Principles

Baseline Comparison is Essential

• Always compare laboratory values to the patient's known baseline, as chronic abnormalities are common in sickle cell disease and acute changes are more clinically significant than absolute values 1, 2
• Do not rely solely on hemoglobin levels to determine transfusion need—consider baseline hemoglobin and clinical status together 1, 2

Context-Dependent Interpretation

• Laboratory abnormalities must be interpreted within the clinical presentation context 1, 2
• Hemoglobin drops are more significant than absolute values, as baseline hemoglobin in HbSS patients is chronically low 1, 2

Common Pitfalls to Avoid

• Do not delay obtaining blood cultures before starting antibiotics if infection is suspected, as bacteremia is more common in younger patients 3
• Clearly communicate the sickle cell disease diagnosis on laboratory request forms to ensure appropriate processing and interpretation 1, 2
• Monitor for treatment complications including fluid overload and transfusion reactions 1, 2
• Do not assume a normal initial chest X-ray excludes acute chest syndrome, as infiltrates can develop 24 hours after admission for vaso-occlusive crisis 5
• Recognize that severe hypoxia in adults cannot be predicted by physical examination or routine laboratory findings alone—arterial blood gas is essential when acute chest syndrome is suspected 3