What is the appropriate diagnosis and treatment for a patient with anemia, leukocytosis, and abnormal differential counts?

Diagnostic Interpretation: Myeloproliferative Disorder with Inflammatory Features

This patient's laboratory findings—microcytic anemia (MCV 77), leukocytosis with neutrophilia, thrombocytopenia, and markedly elevated RDW (28.6)—most likely represent a myeloproliferative neoplasm (MPN) or myelodysplastic syndrome (MDS), potentially complicated by concurrent iron deficiency or inflammatory disease.

Critical Laboratory Abnormalities

The constellation of findings requires immediate hematologic evaluation:

• Microcytic anemia (Hgb 8.6, MCV 77) with extremely elevated RDW (28.6) indicates either severe iron deficiency, coexisting deficiencies, or a clonal hematologic disorder 1
• Leukocytosis (WBC 13) with neutrophilia (11) combined with thrombocytopenia (98) and lymphopenia (0.83) suggests bone marrow dysfunction rather than reactive changes 2
• Monocytosis (0.85) in the setting of cytopenias raises concern for chronic myelomonocytic leukemia (CMML) or other MDS/MPN overlap syndrome 2

Immediate Diagnostic Workup Required

Essential First-Line Testing

• Peripheral blood smear examination to assess for dysplasia, blasts, abnormal monocytes, and red cell morphology 2, 1
• Reticulocyte count to distinguish production defects from hemolysis or blood loss 1, 3
• Iron studies (ferritin, transferrin saturation, serum iron, TIBC) to evaluate for iron deficiency versus anemia of chronic disease 1, 4
• Inflammatory markers (CRP, ESR) as inflammation alters iron study interpretation and may indicate underlying chronic disease 2, 1
• Comprehensive metabolic panel including LDH (elevated in MPNs and hemolysis), liver enzymes, renal function, and albumin 2

Critical Second-Line Evaluation

• Bone marrow aspiration and biopsy with cytogenetics is mandatory given the combination of cytopenias, leukocytosis, and abnormal differential 2
• Conventional cytogenetic analysis to detect clonal abnormalities characteristic of MDS (del 5q, monosomy 7, trisomy 8) or MPN 2
• Molecular testing for JAK2 V617F mutation (present in most MPNs), and consider CMML-associated mutations (TET2, SRSF2, ASXL1, RAS) 2
• Flow cytometry immunophenotyping to detect aberrant monocytic markers (CD56 overexpression, abnormal CD14/CD16) and assess for blast population 2

Differential Diagnosis Priority

Most Likely: Myelodysplastic/Myeloproliferative Neoplasm

The combination of microcytic anemia, thrombocytopenia, leukocytosis with monocytosis, and markedly elevated RDW strongly suggests:

1. CMML (chronic myelomonocytic leukemia): Monocytosis >1×10⁹/L with dysplasia and cytopenias is characteristic 2
2. MDS with excess blasts: Cytopenias with leukocytosis can occur in higher-risk MDS 2
3. Primary myelofibrosis: Anemia, thrombocytopenia, and leukocytosis with elevated LDH are typical 2

Alternative Considerations

• Severe iron deficiency with reactive leukocytosis: However, thrombocytopenia argues against this, as iron deficiency typically causes thrombocytosis 1
• Anemia of chronic disease with infection/inflammation: The microcytosis and thrombocytopenia make pure inflammatory anemia less likely 4, 5
• Mixed deficiency anemia: The extremely high RDW (28.6) indicates coexisting deficiencies, but does not explain the leukocytosis and thrombocytopenia 1, 3

Management Algorithm

Immediate Actions (Within 24-48 Hours)

1. Obtain peripheral blood smear and reticulocyte count to assess for blasts, dysplasia, and bone marrow response 2, 1
2. Check iron studies with inflammatory markers (ferritin, transferrin saturation, CRP) to distinguish iron deficiency from anemia of chronic disease 1, 4
3. Order comprehensive metabolic panel with LDH to assess for hemolysis, tumor lysis risk, and organ dysfunction 2
4. Rule out infectious causes including blood cultures and stool studies if clinically indicated 2

Urgent Hematology Referral Indicated

Refer to hematology immediately for bone marrow evaluation given:

• Unexplained cytopenias with leukocytosis 2, 3
• Monocytosis with thrombocytopenia suggesting MDS/MPN overlap 2
• Potential for rapid progression to acute leukemia in higher-risk disease 2

Risk Stratification Pending Bone Marrow Results

If MDS is confirmed, use IPSS-R scoring (incorporating cytogenetics, blast percentage, and cytopenias) to determine prognosis and treatment urgency 2

For CMML, assess CPSS score (incorporating WBC, hemoglobin, cytogenetics, and blast percentage) to guide therapy 2

Critical Pitfalls to Avoid

• Do not assume simple iron deficiency based on microcytosis alone—the thrombocytopenia and leukocytosis with monocytosis indicate a more complex process 1
• Do not delay bone marrow biopsy in patients with unexplained cytopenias and abnormal differential, as early diagnosis of MDS/MPN affects prognosis 2
• Do not interpret ferritin without CRP—inflammation falsely elevates ferritin and can mask concurrent iron deficiency 1, 4
• Do not start empiric iron or B12 supplementation before obtaining diagnostic studies, as this may obscure the underlying diagnosis 1, 3
• Do not overlook the extremely elevated RDW (28.6)—this suggests either severe nutritional deficiency, hemolysis, or dysplastic erythropoiesis requiring investigation 1

Supportive Care Considerations

While awaiting definitive diagnosis:

• Transfusion support for symptomatic anemia (dyspnea, chest pain, severe fatigue) with leukocyte-reduced products if transplant candidate 2
• Platelet transfusion threshold <10,000/μL or for active bleeding given thrombocytopenia of 98,000/μL 2
• Infection prophylaxis if neutropenia develops or recurrent infections occur 2
• Avoid empiric cytoreductive therapy (hydroxyurea) until diagnosis is established, as this may worsen cytopenias in MDS 2