What are White Blood Cells?
White blood cells (WBCs), also called leukocytes, are the immune system's cellular defense against infection, foreign substances, and abnormal cells. The WBC count measures the total number of these cells circulating in the bloodstream.
Types of White Blood Cells
The total WBC count includes five major cell types, each with distinct functions:
- Neutrophils (40-70%): First responders to bacterial infections and acute inflammation
- Lymphocytes (20-40%): B cells and T cells that fight viral infections and coordinate immune responses
- Monocytes (2-8%): Large phagocytes that clean up debris and pathogens
- Eosinophils (1-4%): Combat parasitic infections and mediate allergic reactions
- Basophils (0.5-1%): Release histamine during allergic reactions and inflammation
Why is WBC Count Important?
The WBC count serves multiple critical functions in clinical medicine:
- Infection detection: Elevated WBC often indicates bacterial infection or inflammatory process
- Immune status: Low WBC suggests immunosuppression or bone marrow failure
- Malignancy screening: Markedly elevated or abnormal WBC may indicate leukemia
- Medication monitoring: Tracks effects of chemotherapy, immunosuppressants, or medications causing bone marrow suppression
WBC normal ranges vary slightly by age, with higher counts normal in newborns and young children. Adult ranges are relatively consistent across sex and ethnicity, though some populations may have slightly lower baseline values.
| Population | Normal Range (cells/μL) | SI Units (× 10⁹/L) |
|---|---|---|
| Adults (male and female) | 4,500-11,000 | 4.5-11.0 |
| Newborns (0-1 week) | 9,000-30,000 | 9.0-30.0 |
| Infants (1 month-1 year) | 6,000-17,500 | 6.0-17.5 |
| Children (2-10 years) | 5,000-13,500 | 5.0-13.5 |
| Adolescents (11-18 years) | 4,500-13,000 | 4.5-13.0 |
- Ethnic variations: People of African or Middle Eastern descent may have lower baseline WBC (3,500-10,000) without pathology
- Pregnancy: WBC naturally increases during pregnancy, especially in third trimester and labor (can reach 20,000-25,000)
- Time of day: WBC count varies diurnally, typically higher in afternoon/evening
- Exercise: Strenuous exercise can transiently elevate WBC
- Critical values: WBC <2,000 or >30,000 should be reported immediately to provider
Leukocytosis (Elevated WBC Count)
Leukocytosis is defined as WBC >11,000 cells/μL. The differential count identifies which cell type is elevated.
Infections and Inflammation
- Bacterial infections: Typically cause neutrophilic leukocytosis (left shift with immature forms)
- Viral infections: May cause lymphocytic leukocytosis (especially EBV, CMV)
- Parasitic infections: Often cause eosinophilia
- Fungal infections: Variable WBC response, often neutrophilic
- Sepsis: Marked leukocytosis or paradoxical leukopenia in severe cases
Inflammatory and Tissue Damage
- Myocardial infarction: WBC rises within hours, peaks at 2-4 days
- Trauma or surgery: Stress-induced neutrophilia
- Burns: Marked leukocytosis proportional to burn severity
- Inflammatory bowel disease: Chronic elevation during flares
- Autoimmune disorders: Variable elevation (e.g., rheumatoid arthritis, vasculitis)
Hematologic Malignancies
- Acute leukemia: WBC may be low, normal, or extremely elevated; abnormal blasts on differential
- Chronic myeloid leukemia (CML): Marked leukocytosis (often >50,000-100,000)
- Chronic lymphocytic leukemia (CLL): Persistent lymphocytosis, typically mature-appearing cells
Medications and Other Causes
- Corticosteroids: Cause neutrophilic leukocytosis by demargination
- G-CSF/GM-CSF: Growth factors used to boost WBC after chemotherapy
- Lithium: Chronic use causes leukocytosis
- Smoking: Chronic mild elevation in smokers
- Splenectomy: Post-splenectomy leukocytosis and thrombocytosis
Leukopenia (Decreased WBC Count)
Leukopenia is defined as WBC <4,500 cells/μL. Severe leukopenia (<2,000) or neutropenia (<500 neutrophils) significantly increases infection risk.
Bone Marrow Suppression
- Chemotherapy: Predictable nadir 7-14 days after treatment
- Radiation therapy: Damages bone marrow stem cells
- Aplastic anemia: Bone marrow failure affecting all cell lines (pancytopenia)
- Myelodysplastic syndromes: Ineffective hematopoiesis
Medications Causing Leukopenia
- Antibiotics: Beta-lactams, sulfonamides, vancomycin
- Antipsychotics: Clozapine (requires monitoring), phenothiazines
- Anticonvulsants: Carbamazepine, phenytoin, valproic acid
- Antithyroid drugs: Propylthiouracil, methimazole
- Immunosuppressants: Azathioprine, mycophenolate, methotrexate
Infections
- Viral infections: HIV, hepatitis, EBV, CMV, influenza
- Overwhelming sepsis: Consumption of WBCs exceeds production
- Typhoid fever: Classic leukopenia despite bacterial infection
Autoimmune and Other Causes
- Systemic lupus erythematosus (SLE): Autoimmune destruction of WBCs
- Hypersplenism: Enlarged spleen sequesters WBCs
- Nutritional deficiencies: B12, folate, copper deficiency
- Benign ethnic neutropenia: Chronic mild neutropenia in African/Middle Eastern populations (normal variant)
Severity Classification
| Category | WBC Count (cells/μL) | Clinical Implications |
|---|---|---|
| Severe Leukopenia | <2,000 | High infection risk; immediate evaluation needed |
| Mild Leukopenia | 2,000-4,500 | Monitor; consider causes (meds, ethnic variant, mild suppression) |
| Normal | 4,500-11,000 | No concern from WBC standpoint |
| Mild Leukocytosis | 11,000-15,000 | Common in infection, inflammation, stress |
| Moderate Leukocytosis | 15,000-25,000 | Suggests significant infection, inflammation, or stress response |
| Marked Leukocytosis | 25,000-50,000 | Consider serious infection, leukemoid reaction, or hematologic disorder |
| Hyperleukocytosis | >50,000-100,000 | High suspicion for leukemia; risk of leukostasis (medical emergency) |
- CNS symptoms: Altered mental status, headache, vision changes, stroke
- Pulmonary symptoms: Dyspnea, hypoxia (pulmonary leukostasis)
- Treatment: Immediate leukapheresis and/or chemotherapy; avoid transfusions that increase viscosity
Approach to Abnormal WBC Count
Step 1: Always order WBC with differential to identify which cell line is abnormal
Step 2: Review patient history:
- Medications (chemotherapy, antibiotics, immunosuppressants, steroids)
- Recent infections or inflammatory conditions
- Chronic medical conditions (autoimmune, HIV, cancer)
- Family history of blood disorders
Step 3: Consider peripheral blood smear if:
- Markedly elevated WBC (>25,000)
- Unexplained leukopenia or leukocytosis
- Abnormal differential with immature forms
- Suspicion of hematologic malignancy
Step 4: Repeat testing if transient cause suspected (stress, exercise, dehydration)
Factors That Increase WBC
- Medications: Corticosteroids (most common), lithium, G-CSF/GM-CSF, epinephrine, beta-agonists
- Physiologic stress: Exercise, emotional stress, labor/delivery, seizures
- Temperature: Cold exposure can cause transient leukocytosis
- Smoking: Chronic tobacco use causes mild persistent elevation
- Time of day: Diurnal variation with higher counts in afternoon/evening
Factors That Decrease WBC
- Medications: Antibiotics (beta-lactams, sulfonamides), antipsychotics (clozapine), anticonvulsants (carbamazepine, valproic acid), chemotherapy, immunosuppressants
- Nutritional: Vitamin B12 deficiency, folate deficiency, copper deficiency, severe malnutrition
- Infections: HIV, viral hepatitis, overwhelming sepsis
- Alcohol: Chronic alcohol use suppresses bone marrow
Pre-analytical Errors
- Clotted sample: Causes falsely low WBC; redraw required
- Delayed processing: WBCs degrade over time; process within 4 hours
- EDTA-induced clumping: Can cause falsely low platelet count but usually doesn't affect WBC
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