What is the interpretation and recommended work‑up for a complete blood count (CBC) showing hematocrit (HCT) 45.4 %, absolute monocyte count (AMC) 1,140/µL (reference 200–950) and absolute myelocyte count (AMyC) 77/µL (reference 0)?

Interpretation of CBC Abnormalities: Monocytosis and Myelocytes

These laboratory findings—absolute monocytosis (1,140/µL) and circulating myelocytes (77/µL)—indicate a myeloproliferative process requiring immediate JAK2 mutation testing and hematology referral to exclude polycythemia vera or another myeloproliferative neoplasm.

Key Laboratory Findings and Their Significance

Hematocrit 45.4%

• This hematocrit is at the upper limit of normal for men (42–54%) and elevated for women (38–46%), warranting confirmation with repeat measurement and hemoglobin level. 1
• Hemoglobin is more reliable than hematocrit for assessing erythrocytosis because hematocrit can falsely increase by 2–4% with prolonged sample storage, while hemoglobin remains stable. 2
• For women, polycythemia vera diagnostic thresholds are hemoglobin >16.5 g/dL or hematocrit >48%; for men, hemoglobin >18.5 g/dL or hematocrit >52%. 2

Absolute Monocytosis (1,140/µL; reference 200–950)

• This represents a 20% elevation above the upper reference limit, which can occur in myeloproliferative neoplasms, chronic infections, inflammatory conditions, or as part of a reactive process. 3
• Monocyte counts show gender differences, with males having higher mean counts (0.48 ± 0.15 × 10⁹/L) than females (0.39 ± 0.11 × 10⁹/L). 3
• Monocyte counts can decrease with prolonged sample storage at room temperature, so this finding should be confirmed on a fresh specimen analyzed within 6 hours. 4

Myelocytes in Peripheral Blood (77/µL; reference 0)

• The presence of any circulating myelocytes is abnormal and represents a "left shift" indicating either reactive myeloid proliferation or a primary myeloproliferative disorder. 1
• In polycythemia vera, uncontrolled myeloproliferation is defined as platelet count >400 × 10⁹/L AND white blood cell count >10 × 10⁹/L after 3 months of hydroxyurea therapy. 1
• Myelocytes in peripheral blood warrant immediate peripheral smear review and consideration of bone marrow evaluation. 2

Immediate Diagnostic Work-Up

First-Line Laboratory Testing

• Complete blood count with full differential including absolute neutrophil count, platelet count, and red cell indices (MCV, MCH, MCHC, RDW). 2
• JAK2 V617F (exon 14) and JAK2 exon 12 mutation testing—detects mutations in up to 97% of polycythemia vera cases and is the cornerstone molecular test for distinguishing primary from secondary erythrocytosis. 2
• Serum erythropoietin level—subnormal EPO is a WHO minor criterion for polycythemia vera diagnosis. 2
• Iron studies: serum ferritin, transferrin saturation, and serum iron—mean corpuscular volume is unreliable for screening iron deficiency in erythrocytosis. 2
• Inflammatory markers: C-reactive protein to interpret ferritin accurately. 2
• Lactate dehydrogenase (LDH) to assess for tissue hypoxia and cell turnover. 2
• Peripheral blood smear review by a qualified hematologist to identify abnormal morphology and confirm myelocyte presence. 2

Second-Line Testing (Based on Initial Results)

• If JAK2 mutation is positive: unilateral bone marrow aspirate and biopsy with immunohistochemistry to confirm polycythemia vera diagnosis and assess for trilineage myeloproliferation. 2
• If JAK2 mutation is negative: systematic evaluation for secondary causes including sleep study for obstructive sleep apnea, pulmonary function tests, chest imaging for COPD, renal imaging (ultrasound or CT) to exclude erythropoietin-producing tumors, and medication review for testosterone or erythropoietin therapy. 2
• Arterial oxygen saturation measurement—values <92% indicate secondary polycythemia due to hypoxemia. 2

WHO 2016 Diagnostic Criteria for Polycythemia Vera

Major Criteria

1. Hemoglobin >16.5 g/dL (women) or >18.5 g/dL (men) OR hematocrit >48% (women) or >49% (men). 2
2. Presence of JAK2 V617F or functionally equivalent exon 12 mutation. 2
3. Bone marrow biopsy showing hypercellularity with trilineage myeloproliferation (marked erythroid, granulocytic, and megakaryocytic proliferation). 2

Minor Criterion

• Subnormal serum erythropoietin level (below normal reference range). 2

Diagnostic Algorithm

• Diagnosis requires ALL three major criteria OR the first two major criteria PLUS the minor criterion. 2

Differential Diagnosis for These Findings

Primary Myeloproliferative Neoplasms

• Polycythemia vera—characterized by JAK2 mutation, elevated hematocrit, and often accompanied by leukocytosis, thrombocytosis, and splenomegaly. 1
• Essential thrombocythemia—may present with monocytosis and left shift if evolving to myelofibrosis. 1
• Primary myelofibrosis—characterized by leukoerythroblastic blood picture with circulating immature myeloid cells. 2

Secondary Causes of Erythrocytosis

• Smoking-related polycythemia—chronic carbon monoxide exposure causes tissue hypoxia and stimulates erythropoietin production; resolves with smoking cessation. 2
• Obstructive sleep apnea—nocturnal hypoxemia drives erythropoietin production. 2
• Chronic obstructive pulmonary disease—chronic hypoxemia stimulates compensatory erythrocytosis. 2
• Cyanotic congenital heart disease—right-to-left shunting causes arterial hypoxemia and compensatory erythrocytosis. 2
• Erythropoietin-producing tumors—renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, meningioma. 2
• Testosterone therapy—can cause erythrocytosis requiring dose adjustment or discontinuation. 2

Reactive Causes of Monocytosis and Left Shift

• Chronic infection—tuberculosis, subacute bacterial endocarditis, fungal infections. 3
• Inflammatory conditions—inflammatory bowel disease, sarcoidosis, autoimmune disorders. 3
• Recovery from bone marrow suppression—post-chemotherapy, post-infection. 4

Immediate Referral Indications

Refer immediately to hematology if any of the following are present: 2

• JAK2 mutation is positive
• Hemoglobin >20 g/dL with symptoms of hyperviscosity (headache, blurred vision, confusion, bleeding)
• Unexplained splenomegaly on physical examination
• Diagnosis remains unclear after initial workup
• Presence of cytopenias in other cell lines (unexplained anemia, thrombocytopenia, or neutropenia)

Management Considerations Pending Workup

Avoid Premature Phlebotomy

• Therapeutic phlebotomy is indicated ONLY when hemoglobin >20 g/dL AND hematocrit >65% with documented hyperviscosity symptoms after excluding dehydration. 2, 5
• Routine phlebotomy before establishing diagnosis can cause iron depletion, decreased oxygen-carrying capacity, and paradoxically increase stroke risk. 2, 5
• If phlebotomy is performed, replace removed blood volume with equal volume of dextrose or saline to prevent hemoconcentration. 2, 5

Monitor for Thrombotic Risk

• If polycythemia vera is confirmed, maintain hematocrit strictly <45% through phlebotomy to reduce thrombotic risk—the CYTO-PV trial showed this reduces cardiovascular death or major thrombosis from 9.8% to 2.7% (HR 3.91; 95% CI 1.45–10.53; P=0.007). 2, 5
• Initiate low-dose aspirin (81–100 mg daily) as second cornerstone of therapy for thrombosis prevention in confirmed polycythemia vera. 2, 5

Sample Handling for Accurate Results

• Repeat CBC should be analyzed within 6 hours of collection, particularly if transported at room temperature, as monocyte counts decrease and hematocrit falsely increases with prolonged storage. 4, 6
• If delay is anticipated, store sample at 4°C to preserve parameter stability. 4, 6

Common Pitfalls to Avoid

• Do not diagnose polycythemia vera based on hematocrit alone without confirming hemoglobin elevation and obtaining JAK2 mutation testing. 2
• Do not overlook coexisting iron deficiency—it can occur with erythrocytosis and requires iron supplementation rather than phlebotomy. 2
• Do not perform aggressive phlebotomy without adequate volume replacement, as this increases hemoconcentration and stroke risk. 2, 5
• Do not use standard polycythemia vera diagnostic thresholds at high altitude without adjustment—physiologic adaptation can increase hemoglobin by 0.2–4.5 g/dL depending on elevation. 2
• Do not rely on mean corpuscular volume to screen for iron deficiency in erythrocytosis—serum ferritin, transferrin saturation, and iron levels are required. 2