In a 28‑year‑old patient taking metoprolol who presents with palpitations and elevated red blood cell count, hemoglobin, and hematocrit, what is the most urgent next step in management?

Urgent Evaluation for Secondary Polycythemia and Cardiac Workup

In a 28-year-old patient on metoprolol presenting with palpitations and elevated RBC/Hgb/Hct, the most urgent next step is to obtain an ECG, assess for hemodynamic instability, and immediately investigate the cause of polycythemia—particularly hypoxic conditions, sleep apnea, or secondary causes—while evaluating whether the palpitations represent a breakthrough arrhythmia despite beta-blockade. 1

Immediate Assessment Required

Cardiac Evaluation

• Obtain a 12-lead ECG immediately to identify the rhythm causing palpitations and rule out atrial fibrillation, atrial flutter, or ventricular arrhythmias that may be breaking through metoprolol therapy 1
• Check vital signs including heart rate and blood pressure; symptomatic bradycardia (HR <50-60 bpm with symptoms) or tachycardia (HR >110 bpm) on metoprolol suggests inadequate rate control or paradoxical effects 1, 2
• Assess for signs of hemodynamic instability: hypotension, altered mental status, chest pain, or acute heart failure 1

Polycythemia Workup Priority

• The elevated RBC/Hgb/Hct is the critical finding requiring urgent investigation in a young patient, as it suggests either primary polycythemia vera or secondary causes 1
• Measure oxygen saturation and arterial blood gas to assess for chronic hypoxemia, which is the most common secondary cause of polycythemia in young adults 1
• Screen for obstructive sleep apnea with overnight oximetry or polysomnography, as nocturnal hypoxemia commonly drives secondary erythrocytosis and can cause palpitations 1
• Order serum erythropoietin level: low or normal suggests polycythemia vera, while elevated levels point to secondary causes 1

Critical Differential Considerations

Why Polycythemia Matters Here

• Elevated hematocrit increases blood viscosity, raising risk of thrombotic events including stroke, myocardial infarction, and venous thromboembolism—particularly concerning in a young patient 1
• Polycythemia can cause palpitations independently through increased cardiac workload and altered hemodynamics 1
• The combination of polycythemia and palpitations raises concern for underlying cardiopulmonary disease that metoprolol may be masking 1

Metoprolol-Related Considerations

• Metoprolol does not cause polycythemia; in fact, antihypertensive medications (particularly ACE inhibitors and ARBs) are more commonly associated with mild anemia, not erythrocytosis 3
• One older study showed metoprolol can transiently increase platelet count via splenic mobilization, but this does not affect RBC parameters 4
• The palpitations despite metoprolol therapy suggest either inadequate dosing, non-compliance, or a rhythm disturbance requiring alternative management 1, 2

Diagnostic Algorithm

First-Line Testing (Urgent)

• Complete blood count with differential to confirm polycythemia and assess for leukocytosis or thrombocytosis (suggesting myeloproliferative disorder) 1
• Serum erythropoietin level to distinguish primary from secondary polycythemia 1
• Arterial blood gas and pulse oximetry to detect hypoxemia 1
• ECG and continuous telemetry to characterize palpitations 1
• Echocardiogram to assess for structural heart disease, right ventricular dysfunction, or valvular abnormalities 1

Second-Line Testing (Within 1-2 Weeks)

• Sleep study if oxygen saturation is normal during waking hours but sleep apnea is suspected 1
• JAK2 V617F mutation testing if erythropoietin is low/normal, to diagnose polycythemia vera 1
• Chest CT to evaluate for chronic lung disease, pulmonary hypertension, or right-to-left shunt 1
• Renal ultrasound and renal function tests to exclude renal artery stenosis or renal tumors secreting erythropoietin 1

Management Strategy

Immediate Interventions

• If palpitations are due to atrial fibrillation with rapid ventricular response, consider IV metoprolol 5 mg over 1-2 minutes, repeated every 5 minutes up to 15 mg total, targeting HR <110 bpm 1, 2
• However, verify no contraindications first: systolic BP >120 mmHg, HR not <60 bpm, no signs of heart failure, no second/third-degree AV block 1, 2
• If symptomatic bradycardia is present (HR <50 bpm with dizziness), hold metoprolol immediately and administer atropine 0.5 mg IV every 3-5 minutes (maximum 3 mg) 5

Polycythemia Management

• If hematocrit >54% in men or >48% in women, consider therapeutic phlebotomy to reduce thrombotic risk while awaiting definitive diagnosis 1
• Target hematocrit <45% to minimize cardiovascular complications 1
• Initiate aspirin 81 mg daily if polycythemia vera is confirmed, to reduce thrombotic events 1

Metoprolol Optimization

• Verify current metoprolol dose and formulation; for palpitations with suspected paroxysmal atrial fibrillation, target dose is metoprolol tartrate 25-100 mg twice daily or metoprolol succinate 50-400 mg once daily 2
• If palpitations persist despite adequate beta-blockade, consider adding or switching to diltiazem 120-360 mg daily for additional rate control 2
• Never abruptly discontinue metoprolol, as withdrawal increases mortality risk 2.7-fold and can precipitate severe angina or arrhythmias 2, 5

Common Pitfalls to Avoid

Diagnostic Errors

• Do not attribute polycythemia to dehydration without confirming with repeat testing after adequate hydration; true polycythemia persists 1
• Do not assume palpitations are benign anxiety in a young patient with polycythemia; this combination warrants thorough cardiac and pulmonary evaluation 1
• Do not overlook sleep apnea as a unifying diagnosis that can cause both polycythemia (via chronic hypoxemia) and palpitations (via sympathetic activation and arrhythmias) 1

Treatment Errors

• Do not give IV metoprolol if the patient has signs of heart failure, hypotension (SBP <120 mmHg), or bradycardia (HR <60 bpm), as this increases cardiogenic shock risk by 11 per 1,000 patients 1, 2
• Do not delay phlebotomy if hematocrit is severely elevated (>60%), as acute hyperviscosity syndrome can cause stroke or myocardial infarction 1
• Do not start anticoagulation empirically without confirming the diagnosis; polycythemia vera requires aspirin, not anticoagulation, unless atrial fibrillation is documented 1

When to Escalate Care

Indications for Immediate Hospitalization

• Hemodynamically unstable palpitations with hypotension, chest pain, or altered mental status 1
• Hematocrit >60% with symptoms of hyperviscosity (headache, visual changes, confusion) 1
• Symptomatic bradycardia unresponsive to atropine, requiring transcutaneous pacing 5
• New-onset atrial fibrillation requiring urgent cardioversion 1

Indications for Subspecialty Referral

• Hematology referral if JAK2 mutation is positive or erythropoietin is inappropriately low, confirming polycythemia vera 1
• Cardiology referral if palpitations persist despite optimized beta-blockade or if structural heart disease is identified 1, 2
• Pulmonology/sleep medicine referral if sleep apnea or chronic lung disease is suspected 1