Neutophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Large unstained cells

White blood cell differentials are now done on automated flow cytometry instruments in order to provide reproducible data. 10,000 wbcs are classified on the basis of size and peroxidase staining as neutrophils, monocytes or eosinophils (which are all peroxidase positive) and as lymphocytes and large unstained cells (which are peroxidase negative). These large unstained cells (LUC), larger than normal lymphocytes, may be atypical lymphocytes, myeloperoxidase deficient cells or peroxidase negative blasts. Basophils are identified using two angle light scattering, based on their singular resistance to lysis. There will also be an indication of more immature neutrophils (commonly called a left shift) based on the ratio of mono/polymorphonuclear white cells (lobularity index).

Normal Range:

1.8-6.8 K/mL 
0.9-2.9 K/mL 
0.1-0.6 K/mL 
0-0.4 K/mL 
0-0.1 K/mL
0-0.2 K/mL 

A left shift usually suggests infection (rarely leukemia). The reproducibility of 100 cell manual differentials is notoriously poor, because of statistical error in counting and observer variation, however, review of blood smears is useful to visually identify rare abnormal cells, blasts, nucleated rbcs, morphologic abnormalities e.g., hypersegmentation, toxic granulation, sickle cells, target cells, spherocytes, basophilic stippling, and to look for rouleau (stacking of red cells due to increased globulins) and clumped platelets. White blood cell differential is unlikely to be abnormal with a normal wbc count or to be changed if the total wbc count is unchanged.

 

Increased neutrophils: suggests infection (bacterial or early viral, rarely leukemia), acute stress, acute and chronic inflammations, tumor, drugs, DKA.
Decreased neutrophils: suggests aplastic anemia, drug-induced neutropenia (e.g., chloramphenicol, phenothiazine, antithyroid drugs, sulphonamide), folate or B12 deficiency, Chediak-Higashi syndrome, malignant lymphoproliferative disease, physiologic in children up to 4 years. 

 

Increased lymphocytes: viral infection (especially, infectious mononucleosis, pertussis), thyrotoxicosis, adrenal insufficiency disease (ALL, CLL), chronic infection, drug and allergic reactions, autoimmune disease. 
Decreased lymphocytes: immune deficiency syndrome. Comments: 

 

Increased monocytes: inflammation, infection, malignancy, TB, myeloproliferative disorders.
Decreased monocytes: depleted in overwhelming bacterial infection. 

 

Increased eosinophils: allergic states, drug sensitivity reaction, skin disorders, tissue invasion by parasites, periarteritis nodosa, hypersensitivity response to malignancy (e.g. Hodgkin's disease), pulmonary infiltrative disease, disseminated eosinophilic hypersensitivity disease. 
Decreased eosinophils: acute and chronic inflammation, stress, drugs: steroids. 

 

Increased basophils: hypersensitivity reactions, drugs, myeloproliferative disorders (CML, polycythemia vera), myelofibrosis.