What are the potential diagnoses associated with increases or decreases in white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), and platelet count in a Complete Blood Count (CBC) report for an adult patient with no specified medical history or symptoms?

CBC Interpretation: Disease-Specific Parameter Changes

White Blood Cell (WBC) Count Abnormalities

Leukocytosis (WBC ≥14,000 cells/mm³)

The most critical finding is not the total WBC count itself, but rather the presence of a left shift, which has far greater diagnostic significance. 1

• Bacterial infection: Elevated band count ≥1,500 cells/mm³ has the highest likelihood ratio (14.5) for documented bacterial infection 1, 2
• Bacterial infection with left shift: Band percentage ≥16% has likelihood ratio of 4.7 for bacterial infection, even with normal total WBC 1, 3
• Neutrophilia: Percentage of neutrophils ≥90% has likelihood ratio of 7.5 for bacterial infection 1
• Metabolic syndrome: Elevated WBC (mean 6.6 x 10³/mm³) correlates with increasing number of metabolic syndrome risk factors 4
• Hematologic malignancies: Leukemia may present with markedly elevated WBC with abnormal differential 1

Leukopenia (Low WBC)

• Tickborne rickettsial diseases: Leukopenia occurs in up to 53% of patients with Human Monocytic Ehrlichiosis (HME) 1
• Viral infections: Common finding in many viral illnesses 1
• Severe neutropenia (<500 cells/mm³): Indicates high infection risk requiring urgent evaluation 2
• Bone marrow suppression: Chemotherapy, radiation, or bone marrow infiltration by malignancy 1

Lymphocyte Abnormalities

• Lymphocytosis: Suggests viral infection, chronic lymphocytic leukemia, or other lymphoproliferative disorders 2
• Severe lymphopenia (<2,500 cells/mm³ in infants): Should prompt evaluation for severe combined immunodeficiency (SCID) 2

Eosinophilia

• Allergic conditions: Elevated eosinophils suggest allergic reactions 2
• Parasitic infections: Classic finding in helminthic infections 2

Red Blood Cell (RBC) Parameters

Anemia (Low Hemoglobin/Hematocrit)

Use MCV to classify anemia type, then follow with reticulocyte index to determine mechanism: 1, 2

Microcytic Anemia (MCV <80 fL)

• Iron deficiency: Most common cause; confirmed by transferrin saturation <15% and ferritin <30 ng/mL 1
• Thalassemia: Inherited hemoglobin disorder 1
• Anemia of chronic disease: Can present as microcytic 1
• Sideroblastic anemia: Rare cause requiring bone marrow biopsy for diagnosis 1

Normocytic Anemia (MCV 80-100 fL)

• Acute hemorrhage: Check stool guaiac, consider endoscopy 1
• Hemolysis: Positive Coombs test, low haptoglobin, elevated indirect bilirubin 1
• Bone marrow failure: From chemotherapy, radiation, or marrow infiltration 1
• Anemia of chronic inflammation: Common in cancer patients 1
• Renal insufficiency: GFR <60 mL/min/1.73 m², low erythropoietin 1

Macrocytic Anemia (MCV >100 fL)

• Vitamin B12 deficiency: Megaloblastic anemia with low B12 levels 1
• Folate deficiency: Megaloblastic anemia with low folate levels 1
• Myelodysplastic syndrome (MDS): Non-megaloblastic macrocytosis 1
• Alcoholism: Non-megaloblastic macrocytosis 1
• Drug-induced: Hydroxyurea, diphenytoin cause macrocytosis 1

Reticulocyte Index Interpretation

• Low RI (<1.0): Decreased RBC production from iron deficiency, B12/folate deficiency, aplastic anemia, or bone marrow dysfunction 1, 2
• High RI (>2.0): Normal/increased RBC production suggests blood loss or hemolysis 1, 2

Polycythemia (Elevated Hemoglobin/Hematocrit)

• Cyanotic congenital heart disease: Compensatory erythrocytosis; hemoglobin >20 g/dL and hematocrit >65% with symptoms requires therapeutic phlebotomy 1
• Dehydration: Hemoconcentration causes falsely elevated values 1

Platelet Count Abnormalities

Thrombocytopenia (Low Platelets)

Thrombocytopenia requires assessment of underlying mechanism: 2

• Tickborne rickettsial diseases: Thrombocytopenia occurs in up to 94% of HME/HGA patients 1
• Bone marrow suppression: Chemotherapy, radiation, or marrow infiltration 2
• Immune destruction: Immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia 1
• Consumption: Disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP) 1
• 22q11.2 deletion syndrome: Lower average platelet counts, large platelets, reduced platelet quality 1
• Bernard-Soulier syndrome: Rare but severe thrombocytopenia with large platelets 1

Thrombocytosis (Elevated Platelets)

• Giant cell arteritis: Platelet count >400,000/μL has positive likelihood ratio of 3.75 for diagnosis 2
• Metabolic syndrome: Elevated platelet counts (mean 276 x 10³/mm³) in patients with 3-5 metabolic syndrome risk factors 4
• Reactive thrombocytosis: Infection, inflammation, iron deficiency, malignancy 2

Critical Pitfalls to Avoid

• Never rely on automated differential alone: Manual differential is essential to accurately assess band forms and left shift 1, 5, 3
• Do not ignore left shift with normal WBC: Left shift can indicate serious bacterial infection even when total WBC is normal 1, 3
• Do not order tests that won't change management: If results won't alter treatment strategy, testing is not justified 1
• Do not perform repeated routine phlebotomies in cyanotic patients: Risk of iron depletion, decreased oxygen-carrying capacity, and stroke 1
• Do not treat asymptomatic bacteriuria in long-term care residents: Prevalence is 15-50% in non-catheterized residents; positive urine culture does not indicate infection 1

When to Obtain CBC with Manual Differential

Always request manual differential (not automated) when: 1, 5, 3

• Suspected bacterial infection to assess for left shift 1, 5
• Evaluating fever in long-term care facility residents 1
• Monitoring chemotherapy or radiation therapy 1, 2
• Assessing hematologic malignancies 2
• Evaluating unexplained symptoms with potential infectious or hematologic cause 1