In an adult with white blood cell count 11.0 ×10⁹/L, absolute neutrophil count 8,052/µL, red blood cell count 3.76 ×10¹²/L, hemoglobin 10.7 g/dL, hematocrit 34.6 %, mean corpuscular hemoglobin concentration 30.9 g/dL, red cell distribution width 15.8 %, hypoalbuminemia, low total protein and hypocalcemia, what is the most likely diagnosis and what initial work‑up and management should be pursued?

Diagnostic Approach to Normocytic Anemia with Neutrophilia, Hypoalbuminemia, and Hypocalcemia

This laboratory pattern—normocytic anemia (hemoglobin 10.7 g/dL, MCV 89 fL), neutrophilic leukocytosis (WBC 11.0 with absolute neutrophil count 8,052/µL), elevated RDW (15.8%), hypoalbuminemia, low total protein, and hypocalcemia—most strongly suggests anemia of chronic disease superimposed on an underlying inflammatory, infectious, or malignant process, with multiple myeloma being a critical diagnostic consideration given the constellation of hypoalbuminemia, hypocalcemia, and anemia. 1

Immediate Diagnostic Priorities

Laboratory Evaluation to Perform Now

Order the following tests immediately to differentiate between anemia of chronic disease, functional iron deficiency, and bone marrow infiltration:

• Complete iron studies (serum ferritin, transferrin saturation, serum iron, total iron-binding capacity) to distinguish anemia of chronic disease (ferritin >100 µg/L, TSAT <20%) from iron deficiency (ferritin <100 µg/L with inflammation present) 2, 1

• Reticulocyte count and reticulocyte index to determine if this represents decreased RBC production (index <1.0-2.0) versus increased destruction or loss (index >2.0) 1

• Inflammatory markers (C-reactive protein and erythrocyte sedimentation rate) to confirm active systemic inflammation, as CRP and ESR correlate strongly with elevated RDW 3

• Renal function tests (serum creatinine, estimated GFR) because chronic kidney disease with GFR <30 mL/min/1.73 m² produces this exact anemia pattern 1

• Serum protein electrophoresis with immunofixation and serum free light chains to evaluate for multiple myeloma, given the triad of anemia, hypoalbuminemia, and hypocalcemia 1

• Peripheral blood smear to examine for dysplastic features, hypochromic cells despite normal MCV, rouleaux formation (suggesting myeloma), or abnormal white blood cells 1

Critical Clinical Context to Obtain

Ask specifically about:

• Fever patterns and constitutional symptoms (weight loss, night sweats), as neutrophilia with anemia suggests infection, malignancy, or inflammatory disease 2

• Bone pain or pathologic fractures, which combined with hypocalcemia and anemia strongly suggest multiple myeloma 1

• Chronic inflammatory conditions (rheumatoid arthritis, inflammatory bowel disease, chronic infections), as these produce neutrophilia, elevated RDW, and anemia of chronic disease 2, 3

• Medication history over the past 2 months, including NSAIDs (which can cause occult GI bleeding) and drugs causing bone marrow suppression 2, 1

Interpretation of Current Laboratory Values

The Elevated RDW (15.8%) Is Diagnostically Significant

An RDW >14.5% in normocytic anemia indicates:

• Active inflammation, as RDW correlates strongly with CRP and ESR independent of hemoglobin and MCV 3

• Possible underlying iron deficiency masked by concurrent inflammation or B12/folate deficiency, since opposing effects on cell size can maintain normal MCV 1

• Increased mortality risk in chronic disease states, particularly chronic kidney disease, where elevated RDW independently predicts all-cause mortality 4

The Low MCHC (30.9 g/dL) Suggests Evolving Iron Deficiency

MCHC below 31 g/dL indicates hypochromic red cells with decreased hemoglobin content per unit volume, reflecting iron-restricted erythropoiesis even when MCV remains normal. 5

• This pattern occurs in early iron deficiency before microcytosis develops, or when iron deficiency coexists with inflammation 5, 1

• In chronic inflammatory states, functional iron deficiency produces hypochromia despite normal MCV because hepcidin-mediated iron sequestration prevents iron utilization 1

The Neutrophilia (8,052/µL) Narrows the Differential

Neutrophilic leukocytosis in the setting of anemia, hypoalbuminemia, and hypocalcemia suggests:

• Bacterial infection (pneumonia, pyelonephritis, intra-abdominal infection), where neutrophilia combined with elevated CRP >40 mg/L shows high specificity for infection 6

• Adult-onset Still's disease, which presents with neutrophilia (50% of patients have WBC >15×10⁹/L), anemia of chronic disease, hypoalbuminemia, and elevated ferritin 2

• Multiple myeloma, where bone marrow infiltration causes anemia and hypoalbuminemia, while hypercalcemia (not hypocalcemia) is typical—however, hypocalcemia can occur with renal failure or hypoalbuminemia affecting calcium measurement 1

• Malignancy with bone marrow involvement, particularly hematologic malignancies like lymphoma or myelodysplastic syndrome 1

Diagnostic Algorithm Based on Initial Test Results

If Ferritin >100 µg/L and TSAT <20%: Anemia of Chronic Disease

This pattern confirms anemia of chronic inflammation with functional iron deficiency. 1

Next steps:

1. Identify the underlying inflammatory/infectious/malignant process through directed imaging (chest X-ray, CT abdomen/pelvis if infection suspected) and malignancy screening 1

2. Do NOT give iron supplementation when ferritin is markedly elevated, as hepcidin-mediated sequestration prevents utilization and may cause iron overload 1

3. Treat the primary disease (infection, inflammatory condition, malignancy), as anemia severity mirrors disease activity 1

4. Reserve erythropoiesis-stimulating agents only for patients with hemoglobin <10 g/dL who remain symptomatic despite optimal treatment of the underlying condition 1

If Ferritin <100 µg/L or TSAT <16%: True Iron Deficiency

Even with inflammation present, ferritin up to 100 µg/L may represent iron deficiency. 2, 1

Next steps:

1. Investigate for gastrointestinal bleeding with stool guaiac testing immediately 1

2. Initiate iron supplementation (oral or intravenous depending on severity and GI tolerance) 2

3. Recheck CBC in 4-6 weeks to confirm reticulocyte response 1

If Reticulocyte Index <1.0-2.0: Hypoproliferative Anemia

Low reticulocyte count confirms decreased RBC production, suggesting:

• Anemia of chronic disease (most common) 1

• Early chronic kidney disease (check creatinine and GFR) 1

• Bone marrow infiltration or failure (requires bone marrow biopsy if other causes excluded) 1

• Medication-induced bone marrow suppression (review all medications) 1

If Reticulocyte Index >2.0: Increased RBC Destruction or Loss

High reticulocyte count indicates:

• Acute hemorrhage (occult GI bleeding, retroperitoneal bleeding) 1

• Hemolysis (check indirect bilirubin, haptoglobin, LDH, direct antiglobulin test) 1

Indications for Bone Marrow Aspiration and Biopsy

Proceed to bone marrow examination if:

• Serum protein electrophoresis shows monoclonal protein or free light chain ratio is abnormal, confirming multiple myeloma 1

• Peripheral smear shows dysplastic features, blasts, or rouleaux formation 1

• Progressive anemia despite treatment of identified underlying conditions 1

• Unexplained pancytopenia or abnormalities affecting multiple cell lines (though current labs show isolated anemia with neutrophilia) 1

• Comprehensive noninvasive workup fails to identify a cause after completing iron studies, renal function, inflammatory markers, vitamin B12/folate, and imaging 1

Management Principles

Do Not Transfuse Based on Hemoglobin Threshold Alone

Packed red blood cell transfusion is indicated only if:

• Hemoglobin falls below 7-8 g/dL, OR
• Severe symptoms develop (chest pain, resting dyspnea, hemodynamic instability), regardless of numeric hemoglobin value 1

Current hemoglobin of 10.7 g/dL does NOT warrant transfusion in a hemodynamically stable patient. 1

Monitor Response to Treatment

• Repeat CBC in 4-6 weeks after initiating treatment of the underlying condition 1

• Serial reticulocyte measurements serve as a rapid indicator of therapeutic response; an upward trend suggests effective management 1

• For inflammatory conditions, monitor hemoglobin every 6 months for stable disease and more frequently during active inflammation, as recurrence is common (>50% after 1 year) 1

Common Pitfalls to Avoid

• Do not assume anemia of chronic disease without measuring iron studies, as 25-37.5% of patients with chronic inflammatory conditions have concurrent iron deficiency 1

• Do not use ferritin alone to rule out iron deficiency in inflammatory states; transferrin saturation must be added because ferritin behaves as an acute-phase reactant 1

• Do not overlook multiple myeloma in patients with normocytic anemia, hypoalbuminemia, and hypocalcemia—this triad mandates serum protein electrophoresis and free light chains 1

• Do not give iron supplementation when ferritin is markedly elevated (>500 ng/mL), as functional iron deficiency from inflammation will not respond to iron therapy 1