What is the initial workup and treatment for an elderly patient with polycythemia (increased red blood cell count)?

Workup for Polycythemia in an Elderly Patient

All elderly patients with polycythemia require immediate confirmation of diagnosis through JAK2 mutation testing, complete blood count with differential, and bone marrow biopsy to distinguish polycythemia vera from secondary causes and assess for disease progression. 1, 2

Initial Diagnostic Workup

Essential Laboratory Tests

• Confirm erythrocytosis with hemoglobin >16.5 g/dL in men or >16.0 g/dL in women, or hematocrit >49% in men or >48% in women 3, 2
• JAK2 mutation testing is mandatory, as >95% of polycythemia vera patients harbor this mutation, which distinguishes primary from secondary causes 2, 1
• Complete blood count to assess for thrombocytosis (present in 53% of cases) and leukocytosis (present in 49% of cases) 2
• Serum erythropoietin level to help differentiate polycythemia vera (typically low or low-normal) from secondary causes (elevated) 1

Bone Marrow Evaluation

• Bone marrow aspirate and biopsy should be performed at diagnosis to confirm morphologic criteria and rule out prefibrotic myelofibrosis or other myeloproliferative neoplasms 4, 1
• Cytogenetic studies are recommended for prognostic assessment, though failure to perform full genetic characterization at diagnosis is acceptable in routine clinical practice 4
• Additional mutation screening (CALR, MPL, and high-risk mutations like ASXL1, SRSF2) should be encouraged for comprehensive prognostic assessment 4, 1

Exclude Secondary Causes

• Assess for hypoxic conditions: smoking history, sleep apnea screening, chronic lung disease, cardiac right-to-left shunts 2
• Evaluate for renal pathology: renal ultrasound to exclude renal artery stenosis or renal tumors producing erythropoietin 1
• Screen for other secondary causes: testosterone use, carbon monoxide exposure, high-altitude residence 2

Risk Stratification

High-Risk Category (Requires Cytoreductive Therapy)

Elderly patients are automatically classified as high-risk because age >60 years is a major risk factor, regardless of thrombosis history 4, 1

Additional high-risk features include:

• Prior thrombotic event at any age 4, 5
• Leukocytosis (additional thrombosis risk factor) 3
• High JAK2V617F allele burden (risk factor for myelofibrosis progression) 3

Assessment of Thrombotic Risk

• Cardiovascular risk factor evaluation: hypertension, hyperlipidemia, diabetes, smoking status 4, 1
• History of arterial thrombosis (occurs in 16% at or before diagnosis) or venous thrombosis (7% at diagnosis, including splanchnic vein thrombosis) 2, 6
• Platelet count assessment: extreme thrombocytosis (≥1,000-1,500 × 10⁹/L) increases bleeding risk from acquired von Willebrand disease 2, 7

Symptom Assessment

Disease-Related Symptoms to Evaluate

• Microvascular symptoms: erythromelalgia (5.3% of patients), transient visual changes (14%), headaches 2, 6
• Pruritus (present in 33% of patients), particularly aquagenic pruritus after bathing 2, 6
• Constitutional symptoms: night sweats, fatigue, weight loss 4, 1
• Splenomegaly (present in 36% of patients) with associated abdominal discomfort 2, 3

Symptom Burden Monitoring

• Formal symptom assessment should be performed using validated tools every 3-6 months 4, 1
• Progressive symptoms (pruritus, night sweats, fatigue, splenomegaly) are indications for cytoreductive therapy even in otherwise lower-risk patients 4

Baseline Assessments Before Treatment

Pre-Treatment Evaluation

• Baseline hematocrit to establish phlebotomy targets (<45% for men, approximately 42% for women) 4, 1
• Cardiovascular assessment: blood pressure, lipid panel, glucose, ECG 4, 1
• Renal and hepatic function before initiating cytoreductive therapy 1
• Pregnancy testing in women of childbearing age, as this affects cytoreductive drug selection 1, 7

Screening for Complications

• Assess for bleeding risk: history of bleeding, platelet count >1,500 × 10⁹/L (acquired von Willebrand disease risk) 7, 2
• Evaluate for disease progression: progressive leukocytosis, worsening splenomegaly, new constitutional symptoms suggesting transformation to myelofibrosis 4, 1

Common Pitfalls to Avoid

Diagnostic Errors

• Do not accept hematocrit targets of 45-50%, as the CYTO-PV trial definitively showed a 3.91-fold increased risk of cardiovascular death or major thrombosis at these levels compared to <45% 4, 1
• Do not delay JAK2 testing while pursuing extensive workup for secondary causes in patients with classic presentation 2
• Do not overlook splanchnic vein thrombosis as a presenting feature, which can occur in 7% of patients 2, 6

Management Considerations

• Aggressive cardiovascular risk factor management is mandatory and should not be deferred, including mandatory smoking cessation counseling 4, 1
• Do not withhold aspirin unless clear contraindications exist (active bleeding, severe thrombocytopenia, platelet count >1,500 × 10⁹/L with bleeding symptoms) 1, 5
• Perform bone marrow biopsy before initiating cytoreductive therapy to rule out progression to myelofibrosis, which would alter treatment approach 4, 1