What is the next best step for a 71 year old male with polycythemia, elevated red blood cell (RBC) count, hyperhemoglobinemia, elevated hematocrit, and thrombocytopenia?

Management of Polycythemia in a 71-Year-Old Male

The next best step for this 71-year-old male with elevated red blood cell count, hemoglobin, hematocrit, and thrombocytopenia is to test for JAK2 V617F mutation to evaluate for polycythemia vera, followed by serum erythropoietin level measurement. 1

Initial Diagnostic Evaluation

The patient presents with consistent laboratory findings suggestive of polycythemia:

• Elevated RBC: 6.29-6.49 (persistently high over time)
• Elevated hemoglobin: 18.7-19.2 g/dL (well above the threshold of 16.5 g/dL for males)
• Elevated hematocrit: 57.9-58.4% (well above the normal range of 47±6%)
• Thrombocytopenia: 135 (low)
• Elevated RDW: 16.6-17.6

Priority Diagnostic Tests

1. JAK2 V617F mutation testing 2, 1

   • Present in >95% of polycythemia vera cases
   • Helps distinguish primary from secondary polycythemia

2. Serum erythropoietin level 1

   • Low levels suggest primary polycythemia (polycythemia vera)
   • Normal/elevated levels suggest secondary causes

3. Bone marrow biopsy 2

   • To assess for hypercellularity with trilineage growth
   • To evaluate for other myeloproliferative features

Differential Diagnosis

Primary Polycythemia (Polycythemia Vera)

• Most likely given the combination of elevated RBCs, hemoglobin, hematocrit with thrombocytopenia
• The presence of thrombocytopenia rather than thrombocytosis is atypical but can occur in advanced disease 2

Secondary Polycythemia

• Hypoxia-driven: COPD, sleep apnea, high altitude, smoking
• Non-hypoxia-driven: Renal disease, tumors producing erythropoietin
• Would need to measure oxygen saturation and erythropoietin levels 1

Management Algorithm

1. If JAK2 V617F mutation is positive and EPO is low:

   • Diagnosis of polycythemia vera is confirmed
   • Initiate therapeutic phlebotomy to maintain hematocrit <45% 1, 3
   • Start low-dose aspirin (81-100 mg/day) unless contraindicated 1, 3
   • Consider cytoreductive therapy (hydroxyurea) given patient's age >60 years (high-risk) 3, 4

2. If JAK2 is negative but strong clinical suspicion remains:

   • Test for JAK2 exon 12 mutation 2
   • If still negative, evaluate for other myeloproliferative neoplasms

3. If JAK2 is negative and EPO is elevated:

   • Investigate secondary causes:
     • Pulmonary function tests
     • Sleep study
     • Abdominal imaging to rule out renal or hepatic pathology
     • Smoking history

Risk Assessment

This patient is at high risk for thrombotic complications due to:

• Age >60 years
• Elevated hematocrit >55%
• Possible myeloproliferative neoplasm

The combination of thrombocytopenia with polycythemia raises concern for:

• Advanced polycythemia vera with bone marrow fibrosis
• Hyperviscosity causing platelet consumption 2
• Potential evolution to post-polycythemia myelofibrosis 4

Common Pitfalls to Avoid

1. Mistaking relative polycythemia for absolute polycythemia

   • Ensure diagnosis is based on true elevation of red cell mass, not just hemoconcentration

2. Missing secondary causes

   • Always evaluate for hypoxic conditions, smoking, and other causes of secondary polycythemia

3. Inadequate treatment targets

   • Maintaining hematocrit <45% significantly reduces thrombotic risk 3
   • Higher targets provide inadequate protection

4. Overlooking thrombocytopenia

   • The presence of thrombocytopenia in this case may indicate disease progression or hyperviscosity 2
   • May affect antiplatelet therapy decisions

5. Delayed treatment

   • Prompt intervention is necessary as thrombotic events are the most lethal complications 5

The combination of elevated red cell indices with thrombocytopenia strongly suggests a myeloproliferative disorder, most likely polycythemia vera. Establishing the diagnosis through JAK2 mutation testing and erythropoietin levels will guide appropriate management to reduce the significant risk of thrombotic complications in this elderly patient.