What is the significance of elevated red blood cell count, hemoglobin, and hematocrit in a patient with otherwise normal blood cell counts?

Evaluation of Elevated Hemoglobin, Hematocrit, and RBC Count

This patient has mild erythrocytosis (hemoglobin 17.3 g/dL, hematocrit 50.5%) with normal red cell indices and a markedly elevated platelet count (477 K/uL), which requires systematic evaluation to distinguish between relative polycythemia, secondary causes, and polycythemia vera. 1

Immediate Assessment Steps

First, confirm this represents true polycythemia rather than relative polycythemia from plasma volume depletion. 1 The diagnostic thresholds for true polycythemia are hemoglobin >18.5 g/dL in men or >16.5 g/dL in women, and hematocrit >55% in men or >49.5% in women. 1 This patient's values (Hgb 17.3, Hct 50.5%) fall below these thresholds but are still elevated above the reference range, warranting investigation.

Rule Out Relative Polycythemia

• Assess hydration status clinically by reviewing fluid intake, recent losses (vomiting, diarrhea), and diuretic use, as these are the most common causes of apparent polycythemia. 2, 1
• Repeat the CBC after ensuring adequate hydration to determine if values normalize, which would confirm relative polycythemia. 3
• Most factors causing plasma volume depletion are clinically obvious and do not require red cell mass measurements. 2

Comprehensive Laboratory Workup

If erythrocytosis persists after hydration, proceed with:

• Serum ferritin and transferrin saturation to evaluate iron status, as iron deficiency can coexist with erythrocytosis. 1
• Reticulocyte count to assess active erythropoiesis. 1
• C-reactive protein (CRP) to identify inflammatory states. 1
• JAK2 mutation testing (both exon 14 and exon 12) to evaluate for polycythemia vera, particularly given the elevated platelet count which raises suspicion for a myeloproliferative disorder. 1
• Serum erythropoietin level to differentiate primary (low EPO) from secondary (elevated or normal EPO) polycythemia. 1

Significance of the Elevated Platelet Count

The platelet count of 477 K/uL is particularly important in this context. 2 Polycythemia vera is associated with thrombocytosis in many cases, and extreme thrombocytosis can lead to acquired von Willebrand disease, which occurs in more than one-third of PV patients. 2 This combination of mild erythrocytosis with thrombocytosis increases the pretest probability of a myeloproliferative disorder.

Diagnostic Criteria for Polycythemia Vera

PV diagnosis requires either:

• Both major criteria (elevated hemoglobin/hematocrit/RBC mass AND JAK2 mutation) plus at least one minor criterion, OR
• First major criterion plus at least two minor criteria. 1

Evaluate Secondary Causes

If JAK2 is negative and EPO is elevated or normal, investigate:

• Smoking history and carbon monoxide exposure, as smoker's polycythemia results from chronic tissue hypoxia stimulating EPO production and resolves with cessation. 1
• Sleep study if nocturnal hypoxemia is suspected, as obstructive sleep apnea produces nocturnal hypoxemia driving EPO production. 1
• Chronic lung disease (COPD) causing chronic hypoxia. 1
• Testosterone use (prescribed or unprescribed), which can cause erythrocytosis in young adults. 1
• Malignancies producing EPO including renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, and meningioma. 1

Management Approach

Therapeutic phlebotomy is NOT indicated at these levels. 1 Phlebotomy should only be performed when hemoglobin exceeds 20 g/dL and hematocrit exceeds 65% with associated symptoms of hyperviscosity. 1 Repeated routine phlebotomies are contraindicated due to risk of iron depletion, decreased oxygen-carrying capacity, and stroke. 1

If Secondary Cause Identified

• Treat the underlying condition (manage COPD, sleep apnea, discontinue testosterone, address smoking). 1
• For smoker's polycythemia specifically, the condition resolves with smoking cessation. 1

If Polycythemia Vera Diagnosed

• Refer to hematology for management, which typically includes cytoreductive therapy and aspirin. 1
• Monitor for complications including thrombosis and acquired von Willebrand disease. 2

Critical Pitfalls to Avoid

• Do not perform aggressive phlebotomy at these hemoglobin/hematocrit levels, as this can cause iron deficiency, which paradoxically increases stroke risk due to decreased red cell deformability. 1
• Do not overlook coexisting iron deficiency, as iron-deficient red cells have reduced oxygen-carrying capacity and deformability. 1
• If iron deficiency is confirmed in the context of erythrocytosis, provide cautious oral iron supplementation with close hemoglobin monitoring, as rapid increases in red cell mass can occur. 1
• Do not assume this is benign without workup, particularly given the elevated platelet count suggesting possible myeloproliferative disorder. 2, 1

Follow-Up Strategy

• Repeat CBC after hydration to confirm persistent erythrocytosis. 3
• Serial monitoring with repeated measurements is appropriate for borderline elevated values. 1
• If values normalize with hydration, no further workup is needed unless erythrocytosis recurs. 3
• If values remain elevated, proceed with complete diagnostic evaluation as outlined above. 1