Sickle Cell Disease Diagnosis
Sickle cell disease diagnosis requires a comprehensive hemoglobinopathy screen using high-performance liquid chromatography, capillary electrophoresis, mass spectrometry, or gel electrophoresis, which must be confirmed by a second test such as solubility testing or electrophoresis on agar in citrate buffer. 1
Primary Diagnostic Testing
- Newborn screening programs can detect sickle cell disease where available and represent the optimal time for diagnosis 1, 2
- Hemoglobin electrophoresis confirms the presence of hemoglobin S (HbS), the abnormal hemoglobin that defines the disease 1, 3
- A positive sickle solubility test alone is insufficient for diagnosis - it cannot differentiate between heterozygous (trait), compound heterozygous, or homozygous (disease) states 4
- The diagnosis should never be accepted without confirmation by a second, more specific test such as solubility testing or electrophoresis on agar in citrate buffer 5
Critical Diagnostic Pitfall
- Sickle solubility testing can yield false negative results in neonates or heavily transfused patients, making it unreliable as a standalone test 1
- Recent red blood cell exchange transfusion can cause confusing hemoglobin electrophoresis results that may temporarily obscure the diagnosis 6
Comprehensive Laboratory Evaluation at Diagnosis
Once sickle cell disease is confirmed, the following baseline studies establish disease severity and organ function:
Hematologic Assessment
- Complete blood count to document normocytic normochromic anemia - baseline hemoglobin in HbSS patients typically ranges 6-9 g/dL 7, 1
- Reticulocyte count to evaluate bone marrow response to chronic hemolysis 7, 1
- Markers of hemolysis including total and direct bilirubin, which are elevated due to red blood cell breakdown 7, 1
Organ Function Assessment
- Renal function tests (BUN and creatinine) to establish baseline kidney function, as vaso-occlusion can cause acute kidney injury 7, 1
- Liver function tests (AST, ALT, alkaline phosphatase) to assess hepatobiliary involvement 7, 1
- Urinalysis to check for hematuria, proteinuria, or signs of urinary tract infection 7, 1
- Coagulation studies (PT, PTT) to evaluate for baseline coagulopathy 7, 1
Specialized Baseline Studies
- Transcranial Doppler studies for all children to assess stroke risk - this should be performed regularly in children and young people aged <17 years 4, 1
- Echocardiography for patients with signs or symptoms suggestive of pulmonary hypertension, which occurs in approximately 6% of adults with sickle cell disease 4
- Hemoglobin F (fetal hemoglobin) level measurement, as higher HbF levels are associated with milder disease 5
- Sickle cell restriction haplotype and alpha-thalassemia testing, as these genetic factors modify disease severity 5
Disease-Modifying Treatment Options
First-Line Therapy
- Hydroxyurea remains first-line disease-modifying therapy for most individuals with sickle cell disease 2, 8
- Hydroxyurea increases fetal hemoglobin production and reduces red blood cell sickling, thereby reducing the frequency and severity of pain crises 2, 3
FDA-Approved Adjunctive Therapies
L-glutamine (oral powder, 5 grams per packet) is indicated to reduce acute complications in patients ≥5 years of age 9
L-glutamine dosing is weight-based: <30 kg receive 5g twice daily (1 packet per dose); 30-65 kg receive 10g twice daily (2 packets per dose); >65 kg receive 15g twice daily (3 packets per dose) 9
L-glutamine reduced hospitalizations by 33% and decreased mean length of stay from 11 to 7 days compared with placebo 2
L-glutamine demonstrated a 25% reduction in sickle cell crises over 48 weeks (median 3 crises vs 4 with placebo) 9
Crizanlizumab reduced pain crises from 2.98 to 1.63 per year compared with placebo 2
Voxelotor increased hemoglobin by at least 1 g/dL in 51% of patients versus 7% with placebo 2
Curative Therapy
- Hematopoietic stem cell transplant is the only curative therapy currently available 2, 8
- Best results are seen in children with a matched sibling donor, though donor availability remains a significant barrier 2, 8
- Gene therapy to correct the βS point mutation is under investigation as another curative modality 8
Acute Complication Management
Pain Crisis Management
- Pain management requires analgesics, adequate hydration, and in severe cases, parenteral opioids 1, 3
- Patients with sickle cell disease are not more likely to develop addiction to pain medications than the general population 2
- Warmth, oxygen therapy, and maintenance of hydration are essential supportive measures 4
Infection Management
- Prompt treatment of infections is critical due to increased susceptibility from splenic dysfunction 1
- Blood cultures should be taken if the patient becomes pyrexial and antibiotics started if temperature is ≥38.0°C or if there are signs of sepsis 4
- Prophylactic penicillin is a cornerstone of preventive care 4
Acute Chest Syndrome
- Management includes oxygen therapy, antibiotics, and possibly exchange transfusion 1, 10
- Regular monitoring of SpO2 provides early warning of acute chest syndrome 4
- Chest physiotherapy should be provided if the patient is unable to mobilize postoperatively 4
Stroke Management
- Immediate neurological evaluation is required for signs or symptoms suggestive of stroke or transient ischemic attack 4
- Previous transcranial Doppler results from within 12 months should be reviewed, especially in children suspected of having a stroke 7
Important Clinical Considerations
- Baseline laboratory values should be known for comparison, as many patients with sickle cell disease have chronic abnormalities 7, 1
- Do not rely solely on hemoglobin levels to determine the need for transfusion - consider the patient's baseline hemoglobin and clinical status 7, 1
- Clearly communicate the diagnosis of sickle cell disease on all laboratory request forms to ensure appropriate processing and interpretation 7
- Monitor for complications of treatment, such as fluid overload or transfusion reactions 7, 1