What is the purpose and interpretation of a Complete Blood Count (CBC) test in patients with symptoms such as fatigue, weakness, or signs of infection, with or without a prior medical history of conditions like anemia or blood disorders?

Complete Blood Count (CBC): Purpose and Interpretation

Primary Indications for CBC Testing

A CBC with differential should be obtained in all patients presenting with fatigue, weakness, or signs of infection to evaluate for anemia, leukopenia, thrombocytopenia, and evidence of bacterial infection. 1

The CBC serves as a fundamental diagnostic tool that provides critical information about:

• Oxygen-carrying capacity through evaluation of hemoglobin, hematocrit, and red blood cell indices 1
• Immune system function through white blood cell count and differential 1
• Platelet adequacy for hemostasis 1

Interpretation in Suspected Infection

White Blood Cell Assessment

An elevated WBC count (≥14,000 cells/mm³) or left shift (band neutrophils ≥16% or absolute band count ≥1,500 cells/mm³) warrants immediate evaluation for bacterial infection, even in the absence of fever. 1, 2

Key diagnostic thresholds for bacterial infection:

• Absolute band count ≥1,500 cells/mm³ has the highest likelihood ratio (14.5) for documented bacterial infection 1, 2
• Band percentage ≥16% has a likelihood ratio of 4.7 for bacterial infection 1, 2
• WBC count ≥14,000 cells/mm³ has a likelihood ratio of 3.7 for bacterial infection 1

Critical caveat: Manual differential count is essential rather than automated analyzer results, as manual review accurately assesses band forms and other immature neutrophils that automated systems may miss 1, 2

When to Pursue Further Testing

In the absence of fever, leukocytosis, left shift, or specific focal infection signs, additional diagnostic tests may not be indicated due to low yield, though nonbacterial infections cannot be excluded. 1

Interpretation in Fatigue and Weakness

Anemia Evaluation

The CBC identifies anemia and provides initial classification through red blood cell indices:

• Hemoglobin and hematocrit establish presence and severity of anemia 1
• Mean corpuscular volume (MCV) classifies anemia as microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL) 1
• Red cell distribution width (RDW) indicates variation in red blood cell size, elevated in iron deficiency and mixed anemias 3

Reticulocyte Count Interpretation

The reticulocyte count distinguishes hypoproliferative anemia (bone marrow failure) from hemolytic or hemorrhagic anemia (appropriate marrow response). 4

• Reticulocyte index >2% suggests appropriate bone marrow response to anemia (hemolysis or bleeding) 4
• Reticulocyte index <2% suggests hypoproliferative anemia (nutritional deficiency, bone marrow disorder, chronic disease) 4

Special Populations and Contexts

HIV-Infected Patients

A CBC with differential and chemistry panel should be obtained upon initiation of HIV care, as anemia, leukopenia, and thrombocytopenia are common in HIV-infected persons. 1

The CBC also provides baseline data before initiating antiretroviral therapy that may have myelosuppressive effects 1

Older Adults in Long-Term Care

In older adults, left shift has particular diagnostic importance because this population frequently lacks fever and typical infection symptoms due to decreased basal body temperature. 2

CBC should be performed within 12-24 hours of symptom onset (or sooner if seriously ill) in long-term care residents with suspected infection 1

Critical Pitfalls to Avoid

• Do not rely solely on automated differential counts when evaluating for infection—manual differential is required for accurate band assessment 1, 2
• Do not dismiss left shift when total WBC is normal—this combination still indicates significant bacterial infection requiring evaluation 1, 2
• Do not ignore schistocytes on peripheral smear even if "rare"—their presence warrants immediate evaluation for thrombotic microangiopathy, as low counts can occur in early or evolving disease 4
• Do not order CBC in isolation—interpret results in conjunction with clinical presentation, vital signs, and targeted additional testing based on suspected diagnosis 1

Algorithmic Approach to Abnormal CBC

Elevated WBC with Left Shift

1. Confirm with manual differential 1, 2
2. Assess for focal infection source (respiratory, urinary, skin/soft tissue, gastrointestinal) 2
3. Obtain targeted cultures and imaging based on suspected source 1, 2
4. Initiate empiric antibiotics after obtaining cultures 2

Anemia with Fatigue

1. Calculate reticulocyte index 4
2. If elevated (>2%): evaluate for hemolysis (LDH, haptoglobin, bilirubin, direct antiglobulin test) or bleeding 4
3. If low (<2%): evaluate based on MCV—microcytic (iron studies), macrocytic (B12, folate), normocytic (chronic disease, renal function) 1, 4

Thrombocytopenia with Schistocytes

1. Immediately order ADAMTS13 activity and inhibitor titer, LDH, haptoglobin, creatinine, urinalysis 4
2. If ADAMTS13 <10%: initiate plasma exchange and methylprednisolone for thrombotic thrombocytopenic purpura 4
3. If ADAMTS13 >10%: evaluate for atypical hemolytic uremic syndrome with complement testing 4