What is the best treatment for a 64‑year‑old patient with a 40‑year history of smoking one pack per day who has secondary erythrocytosis (hematocrit 62 % and hemoglobin 22 g/dL)?

Treatment of Secondary Erythrocytosis in a Heavy Smoker

The best treatment for this patient is immediate smoking cessation, which will resolve the polycythemia without phlebotomy. 1, 2

Diagnostic Confirmation

This 64-year-old patient with 40 pack-years of smoking and markedly elevated hemoglobin (22 g/dL) and hematocrit (62%) has smoker's polycythemia—a secondary erythrocytosis caused by chronic carbon monoxide exposure from cigarette smoke. 1, 2

• Carbon monoxide binds hemoglobin with 200-250 times greater affinity than oxygen, creating carboxyhemoglobin and triggering compensatory erythropoiesis to maintain tissue oxygenation. 2
• Smokers typically maintain carboxyhemoglobin levels of 3-5%, with approximately 2.5% increase per pack smoked daily; heavy smokers can exceed 10% carboxyhemoglobin. 2
• This chronic tissue hypoxia stimulates erythropoietin production, resulting in elevated red blood cell mass. 1, 2

Primary Treatment: Smoking Cessation

Smoking cessation is the definitive first-line treatment and typically leads to complete resolution of polycythemia. 1, 2, 3

• Cardiovascular risk reduction begins within 1 year of cessation, with return to baseline risk after 5 years. 2
• In documented cases, hemoglobin and hematocrit normalize after smoking cessation; one case showed resolution from hemoglobin 21.8 g/dL and hematocrit 64.8% to normal values. 4, 5
• Serum erythropoietin levels increase within 2 weeks of cessation and remain stable thereafter. 6

Smoking Cessation Interventions

• Combine behavioral counseling with first-line pharmacologic therapy (nicotine-replacement therapy, bupropion, or varenicline) for highest success rates. 2
• These medications are effective and have not been linked to increased cardiovascular events. 2
• Do not recommend e-cigarettes as a cessation tool—they are not risk-free and have been associated with polycythemia development. 2, 4

Phlebotomy: When NOT to Perform

Therapeutic phlebotomy is NOT indicated in this patient. 1, 3

The American Heart Association and American College of Cardiology provide strict criteria that this patient does not meet:

• Phlebotomy is indicated only when hemoglobin >20 g/dL AND hematocrit >65% AND documented hyperviscosity symptoms (headache, blurred vision, confusion, bleeding) are present AND dehydration has been excluded. 1, 3
• This patient has hemoglobin 22 g/dL and hematocrit 62%—the hematocrit threshold of >65% is not met. 1
• Repeated routine phlebotomies are explicitly contraindicated because they cause iron depletion, decreased oxygen-carrying capacity, and paradoxically increase stroke risk. 1, 3, 7

Critical Pitfall to Avoid

• Iron-deficient red blood cells from excessive phlebotomy have reduced deformability and oxygen-carrying capacity, which increases whole blood viscosity and stroke risk rather than decreasing it. 1, 7
• If hyperviscosity symptoms are present, first-line therapy is aggressive rehydration with oral fluids or IV normal saline, not phlebotomy. 1, 7

Initial Workup to Exclude Other Causes

Before attributing erythrocytosis solely to smoking, complete the following evaluation:

• JAK2 mutation testing (exon 14 V617F and exon 12) to exclude polycythemia vera, which is present in up to 97% of PV cases. 1
• Complete blood count with differential to assess for thrombocytosis or leukocytosis suggesting myeloproliferative disorder. 1
• Serum ferritin and transferrin saturation to identify coexisting iron deficiency. 1
• Sleep study if nocturnal hypoxemia is suspected (snoring, witnessed apneas, morning headaches, daytime somnolence). 1, 2
• Pulmonary function tests and chest imaging to evaluate for COPD. 1

Monitoring After Smoking Cessation

• Repeat hemoglobin and hematocrit at 2-4 weeks to assess response to cessation. 2
• Continue monitoring every 6-12 months until values normalize. 1
• Directly assess current smoking behavior at each visit. 2
• Hemoglobin is preferred over hematocrit for monitoring because it remains stable with sample storage, whereas hematocrit can falsely increase by 2-4%. 1

Risk Stratification

• Smoking-induced polycythemia increases blood viscosity and raises ischemic stroke risk approximately 1.8-fold. 2
• The extent of red-cell damage (eryptosis) shows a dose-response relationship with daily cigarette consumption. 2
• This patient's 40 pack-year history represents substantial cumulative exposure requiring urgent intervention. 2

If Polycythemia Vera Is Diagnosed Instead

If JAK2 mutation is positive, management changes completely:

• Maintain hematocrit strictly <45% through therapeutic phlebotomy to reduce cardiovascular death and major thrombotic events (2.7% vs 9.8%, P=0.007). 1, 3
• Initiate low-dose aspirin 81-100 mg daily, which reduces thrombotic complications by up to 60%. 3
• Refer immediately to hematology for cytoreductive therapy consideration. 1