What additional labs and care should be completed for a 36-year-old patient with sickle cell anemia, presenting to the ER with recurrent chest pain and shortness of breath, who has a history of pulmonary embolism (PE) and a recently negative Computed Tomography Angiography (CTA) scan?

Management of Admitted Sickle Cell Patient with Recurrent Chest Pain and Shortness of Breath

This patient requires immediate evaluation for acute chest syndrome (ACS), comprehensive risk stratification with NT-pro-BNP and echocardiography, and assessment for chronic thromboembolic disease given his PE history.

Immediate Diagnostic Workup

Rule Out Acute Chest Syndrome (Critical)

• Obtain chest X-ray immediately to identify new pulmonary infiltrates, as ACS is defined by new infiltrate on imaging plus any of: fever >38.5°C, cough, wheezing, hypoxemia (PaO2 <60 mmHg), tachypnea, or chest pain 1
• ACS carries up to 13% all-cause mortality and occurs in approximately 50% of sickle cell patients, with 80% recurrence rate in those with prior episodes 1
• Measure oxygen saturation and arterial blood gas if hypoxemia is suspected, as this guides severity assessment 1
• The diagnosis requires both radiographic evidence and clinical symptoms—patient self-report of chest pain alone is insufficient for ACS diagnosis 2, 1

Essential Laboratory Studies

• Complete blood count (CBC) to assess for acute hemoglobin drop (>2 g/dL suggests splenic sequestration rather than typical vaso-occlusive crisis) 2
• Comprehensive metabolic panel including liver function tests and creatinine 1
• Cardiac troponin to exclude acute coronary syndrome, as chest pain in sickle cell can have cardiac etiology 1
• Blood cultures before antibiotics if ACS is suspected 1
• Lactate dehydrogenase, bilirubin, and reticulocyte count to assess hemolysis severity 2

Risk Stratification for Mortality and Pulmonary Hypertension

NT-pro-BNP Measurement (High Priority)

• Measure NT-pro-BNP level for mortality risk stratification, as levels ≥160 pg/mL confer a 6.24-fold increased risk of death (95% CI 2.9-13.3) compared to lower levels 3
• Mortality rates correlate with NT-pro-BNP: 6% for levels ≤30 pg/mL, 7% for 31-159 pg/mL, and 26% for ≥160 pg/mL 3
• Elevated NT-pro-BNP identifies patients who benefit most from hydroxyurea therapy, with absolute mortality reduction of 104 per 1,000 patients in the highest risk group 3

Echocardiography with Doppler (Essential but Timing-Dependent)

• Schedule Doppler echocardiography to measure tricuspid regurgitation velocity (TRV) once patient is clinically stable 3
• Critical timing requirement: Perform >4 weeks after hospitalization for ACS or >2 weeks after vaso-occlusive crisis, as TRV is transiently elevated during acute illness 3
• Elevated TRV (≥2.5 m/second) identifies patients at increased risk for venous thromboembolic disease and chronic thromboembolic pulmonary hypertension, amenable to anticoagulation and pulmonary endarterectomy 3
• TRV ≥3.0 m/second confers particularly high mortality risk 3

Assessment for Chronic Thromboembolic Disease

Given History of Prior PE

• Consider ventilation-perfusion (V/Q) scan as the preferred imaging modality for chronic thromboembolic pulmonary hypertension (CTEPH), with sensitivity 96-97.4% and specificity 90-95% 4
• Patients with elevated TRV have higher risk of high-probability V/Q scans and CTEPH 3
• Lower extremity venous ultrasonography should be considered to reduce radiation exposure if recurrent thromboembolism is suspected 4
• Avoid reflexive repeat CT angiography given prior negative CTA and radiation burden concerns 4

Management Priorities During Admission

If ACS is Confirmed

• Administer broad-spectrum antibiotics after obtaining blood cultures, covering typical and atypical organisms 1
• Provide aggressive IV analgesia with opioids using scheduled around-the-clock dosing or patient-controlled analgesia (PCA) 2
• Ensure adequate hydration with IV crystalloid solutions 1
• Supplemental oxygen to maintain adequate saturation 1
• Consult hematology emergently for consideration of exchange transfusion in severe cases 1
• ICU-level monitoring may be required given high mortality risk 1

If ACS is Excluded

• Treat vaso-occlusive pain crisis with aggressive parenteral opioid analgesia 2
• Maintain hydration but avoid fluid overload 1
• Continue evaluation for alternative diagnoses including cardiac ischemia, post-PE syndrome, or cardiac dysfunction 4

Additional Considerations

Systematic Dyspnea Evaluation

• Document detailed dyspnea history including: shortness of breath at rest vs. exertion, exercise tolerance (walking distance, stairs), chest pain with exertion, orthopnea, syncope/presyncope, leg swelling, and abdominal swelling 3
• This structured assessment helps differentiate cardiac vs. pulmonary causes and guides further workup 3

Common Pitfalls to Avoid

• Do not dismiss recurrent presentations as "drug-seeking behavior"—patients with sickle cell disease know their disease best, and their self-report should be trusted 2
• Do not delay echocardiography indefinitely, but ensure it's performed when clinically stable for accurate TRV measurement 3
• Do not overlook cardiac causes—obtain ECG and troponin even with "typical" sickle cell pain, as acute coronary syndrome can present with sharp chest pain 5
• Do not use standard D-dimer cutoffs if considering recurrent PE—age-adjusted thresholds improve specificity in patients over 50 years 4

Long-Term Risk Modification

• Ensure patient is on hydroxyurea if not already prescribed, particularly if NT-pro-BNP is elevated, as this provides significant mortality benefit 3
• Screen for sleep-disordered breathing, as this is associated with elevated TRV and treatable 3
• Aggressively manage comorbid conditions identified during risk stratification 3