Leukocyte (WBC) parameters

White Blood Cells (WBC / Leukocytes) Overview

White Blood Cells (WBCs), also known as Leukocytes, are essential components of the immune system. They circulate in the blood and lymph fluid and are crucial for defending the body against infections (bacteria, viruses, fungi, parasites) and other foreign invaders. They also play roles in inflammation, allergic reactions, and destroying abnormal cells (like cancer cells).

There are five main types of WBCs, each with distinct functions. Evaluating the number and types of WBCs is a standard part of a Complete Blood Count (CBC), often including a "differential" count that specifies the percentage and absolute number of each type.

Total White Blood Cell (WBC) Count

The total WBC count measures the total number of leukocytes in a volume of blood, typically expressed as cells x 10⁹ per liter (x 10⁹/L) or cells per microliter (cells/µL). A typical reference range for adults is approximately 4.0 to 11.0 x 10⁹/L (or 4,000 to 11,000 cells/µL), though ranges can vary slightly between laboratories.

Leukocytosis (High WBC Count)

An increase in the total WBC count above the normal range is called leukocytosis. It can be physiological or pathological.

• Physiological Leukocytosis (Temporary increase, often mild):
  • Strenuous physical exercise (muscular work)
  • Emotional stress, severe pain
  • After eating protein-rich meals
  • Exposure to extreme temperatures (hot or cold)
  • Pregnancy and labor
  • Action of UV rays (less common cause)
  • Newborn infants
• Pathological Leukocytosis (Often indicates underlying disease):
  • Infections: Especially bacterial infections, but also some viral, fungal, parasitic infections.
  • Inflammation: Conditions causing tissue inflammation (e.g., autoimmune diseases, inflammatory bowel disease, pancreatitis).
  • Tissue Necrosis/Damage: Heart attack (myocardial infarction), burns, crush injuries, surgery.
  • Malignancies:
    • Leukemias (acute and chronic) - often very high counts with abnormal cells.
    • Other cancers (can cause a reactive leukocytosis).
  • Intoxications/Poisons: Certain toxins, metabolic states (uremia, diabetic ketoacidosis, eclampsia), gout.
  • Severe Hemorrhage or Hemolysis: Acute anemia can trigger WBC release.
  • Medications: Corticosteroids, lithium, epinephrine.
  • Post-splenectomy states: After removal of the spleen.

Leukopenia (Low WBC Count)

A decrease in the total WBC count below the normal range (typically < 4.0 x 10⁹/L) is called leukopenia. It often results from a decrease in neutrophils (neutropenia). Causes include:

• Certain Infections:
  • Viral infections (e.g., influenza, measles, viral hepatitis, HIV/AIDS).
  • Severe bacterial infections (overwhelming sepsis, typhoid fever, paratyphoid, brucellosis).
  • Some protozoal (malaria) or rickettsial infections.
  • Miliary tuberculosis.
• Bone Marrow Failure/Suppression:
  • Aplastic anemia.
  • Myelodysplastic syndromes (MDS).
  • Infiltration of bone marrow (leukemia, lymphoma, metastatic cancer).
  • Severe nutritional deficiencies (e.g., Vitamin B12, folate).
  • Exposure to radiation.
  • Chemotherapy or certain medications (see below).
• Medications: Numerous drugs can cause leukopenia, including some antibiotics (sulfonamides, chloramphenicol), analgesics (metamizole), antipsychotics (clozapine), anticonvulsants, antihistamines, diuretics, chemotherapy agents, immunosuppressants.
• Autoimmune Disorders: Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) - immune destruction of WBCs.
• Hypersplenism: An enlarged, overactive spleen trapping and destroying blood cells.
• Congenital Disorders: Rare inherited conditions affecting WBC production.
• Severe Debilitation/Cachexia.
• Anaphylactic Shock.

WBC Differential Count

The WBC differential breaks down the total WBC count into the percentages and/or absolute counts of the five main types of leukocytes:

Neutrophils

Neutrophils are the most abundant type of WBC in adults and are crucial first responders to bacterial infections and inflammation. They are phagocytic cells (engulf and destroy microbes).

• Neutrophilia (High Neutrophil Count): An increase in neutrophils. Mechanisms include increased production, accelerated release from bone marrow, shift from marginating pool (cells stuck to blood vessel walls) to circulating pool, or delayed exit into tissues.

  Causes of Neutrophilia

  Reactive Neutrophilia	Neoplastic Neutrophilia
  Bacterial infections (most common cause, esp. pyogenic) Inflammation & Tissue Necrosis (MI, burns, surgery, pancreatitis, vasculitis, gout) Metabolic disorders (DKA, uremia, eclampsia) Certain Drugs (corticosteroids, lithium, G-CSF) Stress (physical/emotional stress, trauma, exercise) Malignant Neoplasms (as a paraneoplastic reaction) Hemorrhage / Hemolysis (acute) Smoking Pregnancy	Chronic Myeloid Leukemia (CML) Other Myeloproliferative Neoplasms (Polycythemia Vera, Essential Thrombocythemia, Primary Myelofibrosis) Chronic Neutrophilic Leukemia (rare)

• Neutropenia (Low Neutrophil Count): A decrease in neutrophils (absolute count < 1.5-2.0 x 10⁹/L, severe < 0.5 x 10⁹/L). Increases risk of infection.
  • Agranulocytosis: A severe form of neutropenia with near-complete absence of granulocytes (neutrophils, eosinophils, basophils). Often defined as absolute neutrophil count (ANC) < 0.5 x 10⁹/L (or sometimes < 0.1-0.2 x 10⁹/L).

  Causes of Neutropenia

  Decreased Production / Bone Marrow Problems	Increased Destruction / Peripheral Causes
  Aplastic anemia Leukemia (infiltrating marrow) Myelodysplastic syndrome (MDS) Chemotherapy / Radiation therapy Certain Medications (drug toxicity) Severe nutritional deficiencies (B12, folate, copper, severe malnutrition) Congenital neutropenias (e.g., cyclic neutropenia, Kostmann syndrome, Chediak-Higashi) Some infections affecting marrow (e.g., parvovirus B19)	Overwhelming infections (sepsis - neutrophils consumed) Autoimmune neutropenia (e.g., in SLE, RA, Felty's syndrome) Drug-induced immune destruction Hypersplenism (splenic sequestration) Viral infections (can cause transient neutropenia) Dialysis

Eosinophils

Eosinophils are involved in combating parasitic infections and modulating allergic inflammatory responses.

• Eosinophilia (High Eosinophil Count): An increase in eosinophils (typically > 0.5 x 10⁹/L).

  Causes of Eosinophilia

  Reactive Eosinophilia

  Neoplastic Eosinophilia

  Allergic Diseases (most common in developed countries): Asthma, allergic rhinitis, eczema (atopic dermatitis), drug allergies, urticaria. Parasitic Infections (major cause worldwide): Especially tissue-invasive helminths (worms) like ascariasis, toxocariasis, trichinosis, schistosomiasis, strongyloidiasis, filariasis, hookworm. Skin Diseases (e.g., pemphigus, dermatitis herpetiformis) Certain Infections (e.g., fungal like coccidioidomycosis, convalescent phase of some bacterial/viral infections) Autoimmune / Connective Tissue Diseases (e.g., eosinophilic granulomatosis with polyangiitis [Churg-Strauss], rheumatoid arthritis) Certain Malignancies (Hodgkin lymphoma, some T-cell lymphomas, solid tumors with necrosis or metastasis) Adrenal insufficiency (Addison's disease) Immunodeficiency Syndromes (e.g., Hyper-IgE syndrome, Wiskott-Aldrich) Hypereosinophilic Syndromes (HES) - some forms are reactive

  Myeloid/Lymphoid Neoplasms with Eosinophilia and gene rearrangement (e.g., involving PDGFRA, PDGFRB, FGFR1) Chronic Eosinophilic Leukemia, NOS Acute Myeloid Leukemia with eosinophilia (e.g., AML with inv(16)) Systemic Mastocytosis Other Myeloproliferative Neoplasms (CML, PV, ET, PMF) can have associated eosinophilia

• Eosinopenia (Low Eosinophil Count): A decrease below detectable levels (often < 0.02 x 10⁹/L) or complete absence (aneosinophilia). Commonly seen during acute stress responses (due to cortisol release), acute bacterial/viral infections (early phase), administration of corticosteroids or ACTH, Cushing's syndrome, and sometimes during shock.

Basophils

Basophils are the least common type of granulocyte and contain histamine and heparin. They play a role in allergic reactions (especially immediate hypersensitivity) and potentially parasitic infections.

• Basophilia (High Basophil Count): Relatively uncommon. Most strongly associated with:
  • Myeloproliferative Neoplasms, especially Chronic Myeloid Leukemia (CML). Also seen in Polycythemia Vera, Essential Thrombocythemia, Myelofibrosis.
  • Hypersensitivity reactions (allergic reactions, sometimes food allergies).
  • Hypothyroidism.
  • Certain infections (e.g., chickenpox, influenza).
  • Ulcerative colitis.
  • Recovery phase of infections.
  • Rarely, basophilic leukemia.
• Basopenia (Low Basophil Count): Difficult to assess reliably due to the very low numbers normally present. May be seen during acute infections, stress, hyperthyroidism, or with corticosteroid treatment. Generally not considered clinically significant on its own.

Monocytes

Monocytes are the largest type of WBC. They circulate in the blood for a short time before migrating into tissues, where they differentiate into macrophages or dendritic cells. They are key phagocytes, process and present antigens to lymphocytes, and produce cytokines.

• Monocytosis (High Monocyte Count): An increase in monocytes (typically > 0.8-1.0 x 10⁹/L).

  Causes of Monocytosis

  Reactive Monocytosis

  Neoplastic Monocytosis

  Chronic Infections (Tuberculosis, subacute bacterial endocarditis, syphilis, brucellosis, fungal infections, protozoal infections like malaria) Recovery phase from acute infections or neutropenia Chronic Inflammatory/Autoimmune Diseases (SLE, RA, inflammatory bowel disease [Crohn's, ulcerative colitis], sarcoidosis, vasculitis like polyarteritis nodosa) Granulomatous Diseases Certain Malignancies (Hodgkin lymphoma, non-Hodgkin lymphoma, solid tumors like carcinoma, sarcoma, multiple myeloma) Post-splenectomy Tetrachloroethane poisoning

  Chronic Myelomonocytic Leukemia (CMML) Acute Myelomonocytic Leukemia (AML M4) Acute Monoblastic/Monocytic Leukemia (AML M5) Juvenile Myelomonocytic Leukemia (JMML) Other Myelodysplastic/Myeloproliferative Neoplasms

• Monocytopenia (Low Monocyte Count): Relatively uncommon. Can be seen in:
  • Aplastic anemia
  • Hairy cell leukemia
  • Acute infections (sometimes transiently)
  • Treatment with corticosteroids or certain chemotherapy agents.

Lymphocytes

Lymphocytes are central to the adaptive immune system. They include T lymphocytes (T cells - involved in cell-mediated immunity, regulating immune responses), B lymphocytes (B cells - produce antibodies), and Natural Killer (NK) cells (part of innate immunity).

• Lymphocytosis (High Lymphocyte Count): An increase in lymphocytes (absolute count varies with age, generally > 4.0 x 10⁹/L in adults).

  Causes of Lymphocytosis

  Reactive (Polyclonal) Lymphocytosis

  Neoplastic (Monoclonal) Lymphocytosis

  Viral Infections (most common cause): Infectious mononucleosis (EBV), Cytomegalovirus (CMV), viral hepatitis, adenovirus, rubella, mumps, HIV (acute phase). Bacterial Infections: Pertussis (whooping cough), tuberculosis, brucellosis, syphilis (secondary/tertiary). Protozoal Infections: Toxoplasmosis. Non-infectious Inflammation/Stress: Hypersensitivity reactions, autoimmune diseases (sometimes), post-vaccination, stress (transient). Smoking (chronic) Post-splenectomy

  Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL) Acute Lymphoblastic Leukemia (ALL) Other Lymphomas with leukemic phase (e.g., mantle cell, follicular, marginal zone) Hairy Cell Leukemia Large Granular Lymphocytic (LGL) Leukemia Prolymphocytic Leukemia (PLL) Heavy Chain Diseases (rare)

• Lymphocytopenia (Low Lymphocyte Count): A decrease in lymphocytes (typically < 1.0-1.5 x 10⁹/L in adults). Can affect T cells, B cells, or NK cells. Causes include:
  • Acute infections (viral like influenza, HIV; severe bacterial sepsis)
  • Immunodeficiency Syndromes (Congenital like SCID; Acquired like AIDS)
  • Autoimmune Diseases (SLE, RA - sometimes)
  • Corticosteroid Therapy / Cushing's Syndrome
  • Chemotherapy / Radiation Therapy
  • Bone Marrow Failure / Aplastic Anemia
  • Certain Malignancies (e.g., Hodgkin lymphoma)
  • Severe illness or stress
  • Malnutrition / Zinc deficiency
  • Renal failure
  • Sarcoidosis / Miliary Tuberculosis

Other Cells Sometimes Noted

Plasma Cells

Plasma cells are mature B lymphocytes specialized in producing large amounts of specific antibodies. They are normally found primarily in the bone marrow and lymphoid tissues, not typically circulating in peripheral blood.

The appearance of plasma cells in the peripheral blood is usually abnormal and may indicate:

• Severe infections or chronic inflammatory states (reactive plasmacytosis, usually low numbers).
• Certain viral infections (e.g., measles, rubella, chickenpox, infectious mononucleosis, viral hepatitis).
• Allergic reactions, serum sickness.
• Multiple Myeloma (a plasma cell malignancy - presence in blood often indicates advanced/aggressive disease).
• Plasma Cell Leukemia (rare, aggressive form of myeloma with high numbers in blood).
• Waldenström Macroglobulinemia or other lymphoproliferative disorders.

Atypical Mononuclear Cells / Reactive Lymphocytes

These terms often refer to lymphocytes that have become activated in response to stimulation, usually viral infections. They appear larger than normal lymphocytes, with more abundant cytoplasm (which may be basophilic or vacuolated) and sometimes irregularly shaped nuclei.

While low numbers can be seen normally, a significant increase in atypical lymphocytes (often >10-20%) is characteristic of:

• Infectious Mononucleosis (caused by Epstein-Barr Virus - EBV): The classic cause.
• Other Viral Infections: Cytomegalovirus (CMV), viral hepatitis, toxoplasmosis, HIV (acute), rubella, adenovirus.
• Drug hypersensitivity reactions.
• Certain vaccinations.
• Stress / Post-surgery.
• Some autoimmune conditions.

It's important to differentiate reactive lymphocytes from malignant cells (blasts) seen in leukemia.

The WBC Count & Differential Test Procedure

• Test Name: Complete Blood Count (CBC) with Differential.
• Sample Type: Whole blood collected in an anticoagulant tube (usually EDTA - purple top).
• Preparation: No fasting or special preparation is generally required.
• Collection: Standard venipuncture (blood draw from a vein).
• Analysis: Performed using automated hematology analyzers. These instruments count the total WBCs and differentiate the main types based on size, complexity, and light scattering properties. If the automated count flags abnormalities or specific criteria are met, a peripheral blood smear is typically made, stained, and examined microscopically by a trained technologist or pathologist to confirm the automated differential, assess cell morphology, and identify abnormal cells (like blasts, plasma cells, atypical lymphocytes).

References

1. National Heart, Lung, and Blood Institute (NHLBI). (n.d.). Blood Tests. NIH. Retrieved from https://www.nhlbi.nih.gov/health/blood-tests
2. Lab Tests Online. (n.d.). White Blood Cell Count (WBC). Retrieved from https://labtestsonline.org/tests/white-blood-cell-count-wbc
3. Lab Tests Online. (n.d.). WBC Differential. Retrieved from https://labtestsonline.org/tests/wbc-differential
4. Mayo Clinic Staff. (n.d.). White blood cell count. Mayo Clinic Patient Care & Health Information. Retrieved from https://www.mayoclinic.org/symptoms/low-white-blood-cell-count/basics/definition/sym-20050615 (Covers low count)
5. Bain, B. J., Bates, I., & Laffan, M. A. (Eds.). (2016). *Dacie and Lewis Practical Haematology* (12th ed.). Elsevier. [Note: Comprehensive hematology laboratory textbook]
6. Hoffman, R., Benz Jr, E. J., Silberstein, L. E., Heslop, H. E., Weitz, J. I., & Anastasi, J. (Eds.). (2017). *Hematology: Basic Principles and Practice* (7th ed.). Elsevier. [Note: Comprehensive clinical hematology textbook]