Leukocytes

Leukocytes (white blood cells) are found mainly in the blood, bone marrow, and lymphoid organs. The size of leukocytes varies from 7 µm for lymphocytes to 20 µm for monocytes. The life span of leukocytes ranges from a few days to several months. Leukocytes perform specific immune defense tasks and are part of the specific and non-specific immune defenses. The proportion of different subsets of leukocytes is assessed with a differential blood count.

The procedure

Material needed

• 3 ml EDTA blood (determined as part of the small blood count); mix tubes thoroughly by swirling immediately after collection.

Preparation of the patient

• Not necessary

Disruptive factors

• None known

Standard values

Age groups		SI units
Adult	4 – 10,000 /μl (4 – 10 /nl)	4 – 10 x 109/l
School-age children (7 to 18 years of age)	4.5 – 14,000 /μl (4.5 – 14 /nl)	4.5 – 14 x 109/l
Infants (up to 6 years of age)	5 – 17,000 /μl (5 – 17 /nl)	5 – 17 x 109/l
Infants up to 1 year	6 – 17,500 /μl (6 – 17 /nl)	6 – 17.5 x 109/l
Newborns, infants up to 4 weeks of age	9 – 30,000 /μl (9 – 30 /nl)	9 – 30 x 109/l

Indications

• Infections
• Malignant (malignant) neoplasms
• Bone marrow damage
• Parasitoses (parasitic diseases)

Interpretation

Interpretation of elevated values (leukocytosis).

• Infections
  • Bacterial infections (exception: tuberculosis, TB).
  • Chronic infections
  • Mycoses (fungal diseases)
  • Parasitoses (parasitic diseases)
• Autoimmune diseases
  • Collagenoses (group of connective tissue diseases caused by autoimmune processes) – systemic lupus erythematosus (SLE), polymyositis (PM) or dermatomyositis (DM), Sjögren’s syndrome (Sj), scleroderma (SSc) and Sharp’s syndrome (“mixed connective tissue disease”, MCTD).
  • Rheumatic fever
  • Rheumatoid arthritis
• Malignant neoplasms (neoplasms, tumorous) including hematologic diseases [see below differentiation of reactive and malignant leukocytosis).
  • Leukemias
    • Acute leukemias (in older adulthood, the leukocyte count may be normal, especially if it develops from a myelodysplastic syndrome (preleukemia))
    • Chronic myeloid leukemia (CML).
  • Lymphoma (z. T.)
  • Malignant (malignant) tumors
  • Myeloproliferative disorders (group of disorders that result in an initial proliferation of cells in at least one cell line):
    • Chronic myeloid leukemia (CML).
    • Essential thrombocythemia (ET) – chronic myeloproliferative disorder (CMPE, CMPN) characterized by chronic elevation of platelets (thrombocytes)
    • Myeloproliferative syndromes (MPS).
    • Osteomyelofibrosis (osteomyelosclerosis, OMF).
    • Polycythaemia vera (PV)
• Metabolic causes (hormonal)
  • Cushing’s disease – group of disorders leading to hypercortisolism (hypercortisolism; excess of cortisol).
  • Hyperthyroidism (hyperthyroidism).
• Myocardial infarction* (heart attack)
• Gout
• Coma
  • Coma diabeticum (diabetic coma)
  • Coma hepaticum (hepatic coma)
  • Coma uraemicum (uremic coma/disorder of consciousness due to terminal renal insufficiency (kidney failure)).
• Rheumatic diseases (inflammatory rheumatic diseases; rheumatoid arthritis).
• Pregnancy*
• Shock*
• Wound healing*
• Condition after splenectomy (splenectomy).
• Exogenous factors
  • Smoking (rapidly reversible after smoking cessation; monocytosis and lymphocytosis may persist for up to five years)
  • Stress
  • Medication
    • Glucocorticoid therapy (increase in leukocytes detectable after only a few hours: granulocytes adhering to the wall of vessels are released into the blood by steroid therapy)).
  • CO intoxications*
  • Extreme temperatures*
  • Traumas*
  • Burns*

* Stressful situations

Interpretation of decreased values (leukopenia; leukocytopenia).

• Infections
  • Viral infections (hepatitis B, hepatitis C, HIV infection, influenza, measles, mononucleosis, mumps, cytomegaly).
  • Bacterial infections (brucellosis, shigella enteritis, typhoid abdominalis/salmonella, tuberculosis, tularemia).
• Parasitoses (malaria, rickettsia, kala azar).
• Autoimmune diseases (Felty syndrome, Reiter’s disease (synonyms: Reiter’s syndrome; Reiter’s disease; arthritis dysenterica; polyarthritis enterica; postenteritic arthritis; posturethritic arthritis; undifferentiated oligoarthritis; urethro-oculo-synovial syndrome; Fiessinger-Leroy syndrome; Engl. Sexually acquired reactive arthritis (SARA)), systemic lupus erythematosus (SLE), Sjögren’s syndrome).
• Leukocyte formation disorders
  • Granulocytopenias, familial.
  • Myelofibrosis (myelodysplasias).
• Exogenous factors
  • Medication
    • Cytostatics
    • See under “Hematoxic drugs.”
  • Radiation therapy (including radiation sickness).

Differentiation: is leukocytosis reactive or malignant (malignant)?

Reactive leukocytosis

• Signs of inflammation
  • Fever, laboratory values such as CRP (acute phase reaction).
  • Smaller, often pressure-dolent (painful on pressure) lymph nodes with intact structure
• Infectious genesis is to be demonstrated, if necessary with appropriate temporal progression.
• Cell count < 30,000 leukocytes/μl (usually < 20,000) [polyclonal proliferation].
• The smear shows a colorful picture with:
  • Proliferation of mature cell forms (segmental nuclei, viral stimulus forms).
  • Immunologically reactive lymphocytosis, no blasts!
• Residual hematopoiesis (rest of hematopoiesis) undisturbed.
• Possibly slight anemia (anemia)
• Reactive thrombocytosis (platelets increased beyond the normal range; often!).

Malignant leukocytosis

• Deterioration of general condition:
  • Weight loss, night sweats, lymphoma.
  • Indolent (“painless”) lymph nodes with destroyed structure.
• Cell count does not represent a safe criterion
• Monoclonal cell populations
  • Monotonous picture in the smear, possibly blastic cells/blasts.
  • Immunological (FACS/fluorescence activated cell sorting) monotypic population.
  • Molecular genetic (rearrangement of immunoglobulins or T-cell receptor).
  • Cytogenetic (translocations).
• Hematopoiesis (hematopoiesis) often disturbed.
• Anemia
• Thrombocytopenia (platelets decreased beyond the normal range).

Differentiation: is a left shift reactive or pathologic?

Definition:A left shift is defined as an increased occurrence of neutrophilic rod-nucleated granulocytes (rod-nucleated neutrophils) or their precursor cells in the peripheral blood.A left shift may or may not be accompanied by granulocytosis (increase in granulocytes in the peripheral blood)! Reactive left shift (mainly neutrophil rod-nucleated granulocytes increased; earlier developmental stages are observed only occasionally); common causes are:

• Bacterial infections
• Inflammatory reactions
• Metabolic changes such as pregnancy, acidosis (hyperacidity) or hyperthyroidism (hyperthyroidism).
• Cell decay or tissue necrosis

Pathological left shift (early developmental stages such as metamyelocytes, myelocytes and promyelocytes to myeloblasts); common causes are:

• Malignant degeneration of pluripotent stem cells in the bone marrow (e.g., myeloproliferative syndrome; leukemias, bone marrow infiltration in malignant tumors and lymphomas, extramedullary hematopoiesis/blood formation outside the bone marrow).

Note: If a monomorphic picture of identical looking blood cells, e.g. blasts or lymphocytes, is found in the smear, there is an urgent suspicion of malignant (malignant) disease. Further clues

• Right shift: right shift is the term used when neutrophil segmental granulocytes are oversegmented (often with four, five, or six segments).This rightward shift is found, among others, in the megaloblastic anemias (anemia (anemia) caused by a deficiency of vitamin B12 or, less frequently, by a deficiency of folic acid), uremia ( terminal renal failure/”severely advanced renal impairment”), and constitutional-anginal.

Further procedure for leukocytosis

• Leukocyte count < 15,000/μl → medical history + differential blood count.
• Leukocyte count > 20,000 /μl → send patient to hematologist immediately!