Neutrophils

Laboratory test

Norm     
Adults
absolute numbers 1.5–4.5×109/l
percentages 40–70%
Children (absolute numbers)
0–1 week 2.9–16.5× 109/l
2 weeks – 3 years 1.8–6.5×109/l
4–13 years 1.8–8.0×109/l
Children (percentages)
0–1 week 30–60%
2 weeks – 3 years 15–40%
4–13 years 40–60%

 

Blood EDTA
Cap violet, smear

Neutrophils – cells found in bone marrow, blood, tissues. In the blood, in addition to segmented and band neutrophils, there is also a very small amount (0.25%) of metamyelocytes (young cells). Therefore, the random finding of individual metamyelocytes without a clear increase in band neutrophil count, without a general increase in leukocyte count in the blood, is not yet a sign of pathology. In the bone marrow, a large proportion of neutrophils are made up of poorly differentiated cells – metamyelocytes, myelocytes, promyelocytes, and myeloblasts. An increase in the percentage of band neutrophils (and other younger forms – metamyelocytes, myelocytes, promyelocytes) in the blood is called a shift to the left in the leukogram. If neutrophil hypersegmentation occurs, it is sometimes called a shift to the right in the leukogram. Formally, such neutrophils can be considered “more mature” than neutrophils with normal segmentation. This feature is characteristic of vitamin B12, folate deficiency anemias. Neutrophil is the main cell in the body that fights infection. If the neutrophil count is significantly reduced (agranulocytosis, treatment with cytostatics), the body’s resistance to infection is greatly reduced.

The average time of cell maturation, during which a differentiated neutrophil is formed from a myeloblast, is 8–10 days. During this differentiation, there are 4–11 mitoses. Under normal conditions, neutrophils remain in the bone marrow for 3–5 more days and only then enter the blood. Neutrophils in the blood last from 2 to 34 hours. Under normal conditions, neutrophils are distributed roughly equally between the marginal (attached to the surface of blood vessels) and circulating pool. Provoking factors: stress, infection, physical exertion, eating, medications, sudden release of catecholamines into circulation increase the circulating pool and decrease the marginal pool. Therefore, in all these cases, the neutrophil count in peripheral blood increases. An even larger reserve of neutrophils is in the bone marrow, lung capillaries, spleen, and liver. This granulocyte reserve is about thirty times higher than their count in circulation. The lifespan of neutrophils is about 13 days (including maturation, differentiation, circulation in the blood, and migration to tissues). Granulocytes in tissues last only 1–2 days. About 1.6×109 neutrophils are produced per day per 1 kg of body weight. The same number of neutrophils degenerate in tissues. Neutrophils are like the most active mitotic organ in humans, easily affected by ionizing radiation, cytostatics, other drugs, toxins, alcohol, etc.

Neutrophilia (neutrophilosis), an increase in neutrophil count, is the most common cause of leukocytosis. If neutrophilia is found, it should prompt a search for the source of infection. Physiological neutrophilia usually does not exceed twice the upper limit of the normal neutrophil range. Although infection usually causes leukocytosis and neutrophilia, it may be that severe bacterial infection occurs without an increase in neutrophil count and a shift to the left in the leukogram. This situation occurs more often in elderly people and debilitated patients. Viral infection can manifest with neutrophilia, but a decrease or normal count of neutrophils is more typical. Neutrophilia due to viral infection should be considered as a bacterial complication. In the case of bacterial infection, the following signs of poor prognosis are: 1) as the infection progresses, there is no neutrophilia and leukocytosis; 2) very pronounced neutrophilia – leukemoid reaction; 3) a significant decrease in absolute lymphocyte count; 4) a large proportion of young cells – metamyelocytes, myelocytes, band neutrophils, etc. Signs indicating recovery include: 1) a temporary increase in monocyte count; 2) eosinophilia; 3) lymphocytosis; 4) a decrease in the percentage of young neutrophil cells; 5) a gradual decrease in neutrophilia.

Neutrophilia with an increase in neutrophil count of more than 30–50×109/l is a leukemoid reaction. A leukemoid reaction can be caused by many factors: infection, hemorrhage, malignant tumors. Along with a high degree of neutrophilia, many young immature neutrophilic leukocytes (myelocytes, metamyelocytes, band cells) are found. Sometimes even promyelocytes and blasts may appear. Leukemoid reactions can be distinguished from chronic myeloid leukemia by several features: 1) in leukemoid reactions, promyelocytes and blasts are less common; 2) an increase in basophils or eosinophils is less likely in leukemoid reactions; 3) Auer rods and the Philadelphia chromosome are signs of myeloid leukemia, not leukemoid reactions; 4) alkaline phosphatase citocheminis indicator increases in leukemoid reactions, but not during leukemias (this indicator should not be confused with alkaline phosphatase activity determined serume); 5) toxic granularity of neutrophils, vacuolization is more characteristic of leukemoid reactions than leukemias; 6) fever is more typical of leukemoid reactions; 7) during treatment of the underlying disease, leukemoid reaction gradually decreases, while during leukemias, the neutrophil count usually does not decrease without specific treatment.

Adult isolated neutropenia is rare. Usually, pathological conditions causing a decrease in neutrophil count also affect erythrocyte and platelet precursors. When the absolute neutrophil count drops to 1.0×109/l or less, the risk of infectious complications increases several times. If neutropenia reaches 0.5×109/l, it is a sign of severe neutropenia. In this case, a rapid bacterial infection may occur even when taking antibiotics. A hematologic analyzer may falsely show a very low neutrophil count if there is paraproteinemia, incorrect use of anticoagulants for blood sampling, or if the analyzer system is clogged (which may also reveal a very proportional “pancytopenia”). The most common causes of neutropenia are: 1) medications and 2) viral infections. Medications can cause neutropenia depending on the dose (especially cytostatics) or independently of the dose (idiosyncratic effect). The following medication groups most commonly exhibit an idiosyncratic effect: phenothiazines, antiepileptic drugs, antithyroid drugs, semi-synthetic penicillins, sulfonamides. Discontinuation of medication should lead to the disappearance of neutropenia within 2-3 weeks.

What additional laboratory tests may be useful when neutropenia is found? If the obvious cause is not immediately apparent, the following laboratory tests could be performed: 1) ANA; 2) determination of rheumatoid factor; 3) determination of vitamin B12 and folic acid; 4) serological reactions (HIV, EBV, viral hepatitis markers). Sometimes, along with leukopenia (neutropenia), other signs of laboratory tests may be observed: 1) signs of megaloblastic anemia (increased MCV, MCH, RDW, Jolly bodies in erythrocytes, neutrophil hypersegmentation); 2) acute leukemia – blasts; 3) bone marrow damage – normoblasts, giant platelets, increased MPV, dacryocytes, polychromatophilia.

Source | Handbook of Basic Laboratory Tests | Doctor of Medical Sciences Gintaras Zaleskis