From Williams haematology 7th Edition

I. Primary lymphocytosis A. Lymphocytic malignancies 1. Acute lymphocytic leukemia (Chap. 91) 2. Chronic lymphocytic leukemia and related disorders (Chap. 92) 3. Prolymphocytic leukemia (Chap. 92) 4. Hairy cell leukemia133 (Chap. 93) 5. Adult T cell leukemia (Chaps. 92 and 96) 6. Lymphoma cell leukemia134 (Chap. 96) 7. Large granular lymphocytic leukemia135 (Chap. 94) a. NK cell leukemia136 (Chap. 94) b. CD8+ T cell large granular lymphocytic leukemia137,138,139 c. CD4+ T cell large granular lymphocytic leukemia53,140 d. / T cell large granular lymphocytic leukemia141 B. Essential monoclonal B cell lymphocytosis6 (Chap. 92) C. Persistent polyclonal B cell lymphocytosis9,10

II. Reactive lymphocytosis A. Mononucleosis syndromes (Chap. 84) 1. Epstein-Barr virus38,142,143,144,145,146 2. Cytomegalovirus41,42,147,148,149,150,151,152 3. Human immunodeficiency virus153,154,155,156,157,158 4. Herpes simplex virus type II 5. Rubella virus 6. Toxoplasma gondii159 7. Adenovirus 8. Infectious hepatitis virus 9. Dengue fever virus160,161,162 10. Human herpes virus type 6 (HHV-6)77,163 11. Human herpes virus type 8 (HHV-8)164 12. Varicella zoster virus165 B. Bordetella pertussis45 C. NK cell lymphocytosis54,55,56,73,75,166,167,168,169 D. Stress lymphocytosis (acute)69 1. Cardiovascular collapse66 a. Acute cardiac failure b. Myocardial infarction 2. Staphylococcal toxic shock syndrome170 3. Drug-induced68,77,171 4. Major surgery 5. Sickle cell crisis172 6. Status epilepticus 7. Trauma65,66 E. Hypersensitivity reactions 1. Insect bites73,74,75 2. Drugs76,78,80,81,173 F. Persistent lymphocytosis (subacute or chronic) 1. Cancer84 2. Cigarette smoking15,174 3. Hyposplenism86 4. Chronic infection a. Leishmaniasis175 b. Leprosy176 c. Strongyloidiasis58,59,60 5. Thymoma83

Leucocytosis: Interpretation

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Leucocytosis: Interpretation

Leucocytosis - an elevation of the total number of white cells in blood, can be caused by a rise in the amount of one or more leucocyte types:
Ø Neutrophilia
Ø Lymphocytosis
Ø Monocytosis
Ø Eosinophilia
Ø Basophilia.

The division of leucocytoses (especially neutrophilias) according to their aetiology is directly useful in clinical diagnostics.

• Infections and inflammations
• Medication-related (corticosteroids, granulocyte growth factors, others)
• Stress-related (physical, emotional)
• Leukaemias (rare in comparison to the previous-mentioned)

Approach
If the clinical picture explains the occurrence and extent of leucocytosis, no specific investigations are required. If the underlying disease is unknown, the leucocyte differential count helps in orientation.

Neutrophilia (> 75% of total WBC count) is the most common form of leucocytosis. Neutrophilia occurs most frequently with infections; the neutrophil count is related to the severity of infection as well as to the microbiological aetiology. Pyogenic cocci (staphylococcus, streptococcus, pneumococcus, gonococcus and meningococcus) and bacilli (E. coli, Proteus and Pseudomonas) are common causes of neutrophilia. The leucocyte count is usually 15 – 30,000/dl, but sometimes even 50 – 80,000/dl. Immature neutrophils (bands, metamyelocytes) and "toxic" granulation are characteristic in the acute phase.

Neutrophilia is also relatively common in non-pyogenic infections. These include rheumatic fever, diphtheria, polio, typhoid fever, cholera, and shingles. The leucocyte count is usually 12 – 18,000/dl.

Sometimes neutrophil leucocytosis with immature granulocytes is so marked that it is called a leukaemoid reaction.

Other causes of neutrophil leucocytosis include:
- Bleeding
- Trauma
- Cardiac diseases (infarction, atrial fibrillation)
- Drugs (e.g. corticosteroids), poisonings
- Metabolic diseases (renal insufficiency, diabetic coma, gout attack, eclampsia)
- Blood diseases: myeloid leukaemias and polycythaemia vera
- Rheumatoid arthritis, vasculitis
- Blood transfusion

Eosinophilia is relatively common (> 6% of total WBC count). It is a manifestation of nasal/ respiratory allergy. The absolute count is more significant that % alone (Total WBC X eosinophil % = absolute count). A count above 700 is considered pathological and warrants treatment

Lymphocytosis (> 40% of total WBC count) is also relatively common. Infants and younger children have a high lymphocyte count with normal WBC count and may be as high as 50-60%

Marked lymphocytosis is seen in acute/ chronic lymphocytic leukaemia, infectious mononucleosis and in pertussis.

Milder lymphocytosis is common in various infections.

Monocytosis (> 0.8% of total WBC count) is uncommon. It can be associated with various infections (typhoid fever, brucellosis, tuberculosis, subacute endocarditis, malaria), rheumatoid arthritis and other connective tissue diseases, Hodgkin's disease and monocytic leukaemias.

Basophilia is rare. It is sometimes seen in the accelerated phase of chronic myeloid leukaemia (CML)

Further Investigations

Bone marrow examination is necessary if the aetiology of leucocytosis remains unknown, especially if the white cell differential count or the clinical picture indicates the possibility of a haematological malignancy.

If the symptoms and findings are unremarkable, follow-up of 1 - 2 weeks and a new leucocyte count may be the method of choice. A significant proportion of underlying conditions (infections) are harmless and temporary. Treatment is directed against the cause of leucocytosis.

Tips

• A severe infection as a cause of leucocytosis should be urgently recognized and therapy initiated.
• Leucopenia or a normal leucocyte count, on the other hand, does not necessarily exclude a severe infection.
• Leucocytosis of unknown origin may be associated with rheumatic diseases, other chronic inflammations or haematological malignancies. The cause of leucocytosis can usually be revealed with a small number of investigations.