What to do if all CBC (Complete Blood Count) parameters are normal except for an elevated hematocrit (Hct) level in a patient on clopidogrel (Plavix) for a heart stent?

Elevated Hematocrit in a 64-Year-Old Male on Clopidogrel Post-Stent

This isolated elevation in hematocrit to 53% requires immediate investigation for secondary polycythemia causes (smoking, COPD, sleep apnea, renal pathology) and consideration of primary polycythemia vera, as the elevated hematocrit increases thrombotic risk that could lead to catastrophic stent thrombosis—a complication with 20-45% mortality. 1

Immediate Clinical Assessment

Critical Risk Evaluation

• Assess thrombotic risk factors urgently, as stent thrombosis presents as STEMI in most cases and survivors remain at high risk for recurrent thrombosis 1
• Determine time since stent placement, as the highest risk period is within the first 30 days, with ongoing risk of 0.2-0.6% per year thereafter 1
• Verify clopidogrel adherence, as nonadherence to dual antiplatelet therapy (DAPT) is the most common cause of acute stent thrombosis 1

Secondary Polycythemia Workup

• Evaluate for hypoxic conditions: smoking history, chronic obstructive pulmonary disease, sleep apnea, and high-altitude exposure as these are the most common causes of secondary erythrocytosis
• Assess renal function and imaging: check for renal artery stenosis, polycystic kidney disease, or renal cell carcinoma that can produce excess erythropoietin
• Review medication list: testosterone replacement, anabolic steroids, and erythropoietin-stimulating agents can elevate hematocrit

Primary Polycythemia Vera Screening

• Order JAK2 V617F mutation testing if secondary causes are excluded, as this is present in >95% of polycythemia vera cases
• Measure erythropoietin level: low or inappropriately normal levels suggest primary polycythemia vera
• Check for associated findings: splenomegaly, pruritus after bathing, erythromelalgia, or thrombotic history

Management Strategy

Immediate Thrombotic Risk Mitigation

• Continue clopidogrel 75mg daily without interruption, as discontinuation dramatically increases stent thrombosis risk 1
• Verify aspirin continuation at 75-100mg daily (or 162-325mg if within acute phase), as DAPT is essential for stent protection 1
• Consider therapeutic phlebotomy if hematocrit >54% to reduce hyperviscosity and thrombotic risk while awaiting definitive diagnosis

Clopidogrel Response Assessment

• Consider platelet function testing in this high-risk scenario, as patients with high platelet reactivity despite clopidogrel have increased rates of major adverse cardiac events including stent thrombosis 1
• Evaluate for clopidogrel resistance, which occurs in 15-31% of patients and is associated with higher pretreatment platelet reactivity 2
• If high platelet reactivity is documented, alternative P2Y12 inhibitors such as prasugrel or ticagrelor should be considered 1

Genetic and Pharmacologic Considerations

• CYP2C19 genetic testing may be considered in this high-risk patient, as reduced-function alleles result in diminished clopidogrel metabolism, lower active metabolite levels, and higher rates of cardiovascular events 1
• However, routine genetic testing is not recommended (Class III) unless the patient is undergoing high-risk procedures 1

Ongoing Monitoring

Hematologic Surveillance

• Repeat CBC weekly initially to track hematocrit trends and assess for other cytopenias that might suggest myeloproliferative disorder
• Monitor for thrombocytosis or leukocytosis which, combined with elevated hematocrit, would strengthen suspicion for polycythemia vera
• Watch for rare clopidogrel-associated hematologic toxicity including thrombocytopenia, neutropenia, or leukopenia, though these typically occur within the first 2-3 months of therapy 3, 4

Cardiovascular Monitoring

• Assess for symptoms of myocardial ischemia including chest pain, dyspnea, or anginal equivalents that could indicate inadequate platelet inhibition 1
• Maintain DAPT duration based on stent type: minimum 12 months for drug-eluting stents, minimum 1 month (ideally up to 12 months) for bare-metal stents 1

Common Pitfalls to Avoid

• Never discontinue clopidogrel abruptly without cardiology consultation, as this is the leading cause of stent thrombosis with devastating consequences 1
• Do not assume clopidogrel is providing adequate platelet inhibition without testing in high-risk scenarios, as significant interindividual variability exists 2
• Avoid overlooking secondary causes of polycythemia before pursuing expensive workup for primary disorders
• Do not delay phlebotomy if hematocrit remains significantly elevated, as hyperviscosity compounds the already elevated thrombotic risk from coronary disease and stenting