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Neutrophilia is an increase in the absolute neutrophil count in the peripheral circulation. Normal blood values vary by age. Neutrophilia can be caused by a direct problem with blood cells (primary disease). It can also occur as a consequence of an underlying disease (secondary). Most cases of neutrophilia are secondary to inflammation.
Primary causes
- Conditions with normally functioning neutrophils – hereditary neutrophilia, chronic idiopathic neutrophilia
- Pelger–Huet anomaly
- Down syndrome
- Leukocyte adhesion deficiency
- Familial cold urticaria
- Leukemia (chronic myelogenous (CML)) and other myeloproliferative disorders
- Surgical removal of spleen
Secondary causes
- Infection
- Chronic inflammation – especially juvenile rheumatoid arthritis, rheumatoid arthritis, Still's disease, Crohn's disease, ulcerative colitis, granulomatous infections (for example, tuberculosis), and chronic hepatitis
- Cigarette smoking – occurs in 25–50% of chronic smokers and can last up to 5 years after quitting
- Stress – exercise, surgery, general stress
- Medication induced – corticosteroids (for example, prednisone, β-agonists, lithium)
- Cancer – either by growth factors secreted by the tumor or invasion of bone marrow by the cancer
- Increased destruction of cells in peripheral circulation can stimulate bone marrow. This can occur in hemolytic anemia and idiopathic thrombocytopenic purpura
Neutrophilia (also called neutrophil leukocytosis or occasionally neutrocytosis) is leukocytosis of neutrophils, that is, a high number of neutrophil granulocytes in the blood.
Granulocytopenia is an abnormally low concentration of granulocytes in the blood. This condition reduces the body's resistance to many infections. Closely related terms include agranulocytosis (etymologically, "no granulocytes at all"; clinically, granulocyte levels less than 5% of normal) and neutropenia (deficiency of neutrophil granulocytes). Granulocytes live only one to two days in circulation (four days in spleen or other tissue), so transfusion of granulocytes as a therapeutic strategy would confer a very short-lasting benefit. In addition, there are many complications associated with such a procedure.
There is usually a granulocyte chemotactic defect in individuals suffering from insulin-dependent diabetes mellitus.
Neutrophils are the primary white blood cells that respond to a bacterial infection, so the most common cause of neutrophilia is a bacterial infection, especially pyogenic infections.
Neutrophils are also increased in any acute inflammation, so will be raised after a heart attack, other infarct or burns.
Some drugs, such as prednisone, have the same effect as cortisol and adrenaline (epinephrine), causing marginated neutrophils to enter the blood stream. Nervousness will very slightly raise the neutrophil count because of this effect.
A neutrophilia might also be the result of a malignancy. Chronic myelogenous leukemia (CML or chronic myeloid leukaemia) is a disease where the blood cells proliferate out of control. These cells may be neutrophils. Neutrophilia can also be caused by appendicitis and splenectomy.
Primary neutrophilia can additionally be a result of Leukocyte adhesion deficiency.
White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from multipotent cells in the bone marrow known as hematopoietic stem cells. Leukocytes are found throughout the body, including the blood and lymphatic system.
All white blood cells have nuclei, which distinguishes them from the other blood cells, the anucleated red blood cells (RBCs) and platelets. Types of white blood cells can be classified in standard ways. Two pairs of broadest categories classify them either by structure (granulocytes or agranulocytes) or by cell division lineage (myeloid cells or lymphoid cells). These broadest categories can be further divided into the five main types: neutrophils, eosinophils (acidophilus), basophils, lymphocytes, and monocytes. These types are distinguished by their physical and functional characteristics. Monocytes and neutrophils are phagocytic. Further subtypes can be classified; for example, among lymphocytes, there are B cells, T cells, and NK cells.
The number of leukocytes in the blood is often an indicator of disease, and thus the WBC count is an important subset of the complete blood count. The normal white cell count is usually between 4 × 10/L and 11 × 10/L. In the US this is usually expressed as 4,000 to 11,000 white blood cells per microliter of blood. They make up approximately 1% of the total blood volume in a healthy adult, making them substantially less numerous than the RBCs at 40% to 45%. However, this 1% of the blood makes a large difference to health, because immunity depends on it. An increase in the number of leukocytes over the upper limits is called leukocytosis. It is normal when it is part of healthy immune responses, which happen frequently. It is occasionally abnormal, when it is neoplastic or autoimmune in origin. A decrease below the lower limit is called leukopenia. This indicates a weakened immune system.
Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes (PMN, PML, or PMNL) because of the varying shapes of the nucleus, which is usually lobed into three segments. This distinguishes them from the mononuclear agranulocytes. In common parlance, the term "polymorphonuclear leukocyte" often refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types (eosinophils, basophils, and mast cells) have lower numbers. Granulocytes are produced via granulopoiesis in the bone marrow.
Morning pseudoneutropenia is a transient reduction in the measured neutrophil count from peripheral samples. This is noticed in some patients who are taking antipsychotic medication. Morning pseudoneutropenia is thought to be due to diurnal variation in the amount of circulating white blood cells and changes in the levels of hematopoietic cytokines and granulocyte colony stimulating factor (GCSF). Antipsychotics may amplify the natural variation in these hematopoietic factors.
Neutropenia is a hematological disorder characterized by an abnormally low number of neutrophils in the blood. Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defense against infections. There is some variability in the neutrophil counts depending upon when the sample is taken, where the blood sample is taken from, and the system used by the medical lab for measuring the blood cells, but any significant reduction in function or number below the appropriate range may predispose individuals to infections.
Case reports of such incidences are reported with Clozapine and Risperidone and Aripiprazole.
These case reports suggest that the observed cases of the morning pseudoneutropenia did not proceed to become agranulocytosis which is a significant and dangerous side effect of some of antipsychotics. Hence it was suggested that although the morning neutrophil count may appear low, if the antipsychotic medication were considered efficaceous then white cell counts may be repeated in the afternoon prior to making a decision based only on the morning counts.
Treatment consists mainly of high dose antibiotics for active infections and prophylactic antibiotics for prevention of future infections. GM-CSF therapy or bone marrow transplant might be considered for severe cases. Prognosis is difficult to predict, but patients receiving treatment are generally able to survive to adulthood.
Neutrophils (also known as neutrocytes) are the most abundant type of granulocytes and the most abundant (40% to 70%) type of white blood cells in most mammals. They form an essential part of the innate immune system. Their functions vary in different animals.
They are formed from stem cells in the bone marrow. They are short-lived and highly motile, or mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or bands). They form part of the polymorphonuclear cells family (PMNs) together with basophils and eosinophils.
The name "neutrophil" derives from staining characteristics on hematoxylin and eosin (H&E) histological or cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinophilic white blood cells stain bright red, neutrophils stain a neutral pink. Normally, neutrophils contain a nucleus divided into 2–5 lobes.
Neutrophils are a type of phagocyte and are normally found in the bloodstream. During the beginning (acute) phase of inflammation, particularly as a result of bacterial infection, environmental exposure, and some cancers, neutrophils are one of the first-responders of inflammatory cells to migrate towards the site of inflammation. They migrate through the blood vessels, then through tissue, following chemical signals such as Interleukin-8 (IL-8), C5a, fMLP, Leukotriene B4 and HO in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance.
Neutrophils are recruited to the site of injury within minutes following trauma, and are the hallmark of acute inflammation; however, due to some pathogens being indigestible, they can be unable to resolve certain infections without the assistance of other types of immune cells.
Neutrophils display highly directional amoeboid motility in infected footpad and phalanges. Intravital imaging was performed in the footpad path of LysM-eGFP mice 20 minutes after infection with "Listeria monocytogenes".
A lymphocyte is one of the subtypes of white blood cell in a vertebrate's immune system. Lymphocytes include natural killer cells (Phagocytes) (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adaptive immunity), and B cells (for humoral, antibody-driven adaptive immunity). They are the main type of cell found in lymph, which prompted the name "lymphocyte".
Estimation of the frequency of SGD is difficult, as it is an extremely rare disease with few cases reported in literature. The condition was first reported in 1980, and since only a handful more cases have been published.
In cardiovascular disease, increased white blood cell counts have been shown to indicate a worse prognosis.
It is believed that cytokines (including IL-1 and TNF) accelerate the release of cells from the postmitotic reserve pool in the bone marrow, leading to an increased number of immature cells.
This form usually lessens in severity within two years of diagnosis.
The use of prophylactic antibiotics has been proposed.
See article at BioMed Central site:
Certain medications can alter the number and function of white blood cells.
Medications that can cause leukopenia include clozapine, an antipsychotic medication with a rare adverse effect leading to the total absence of all granulocytes (neutrophils, basophils, eosinophils). The antidepressant and smoking addiction treatment drug bupropion HCl (Wellbutrin) can also cause leukopenia with long-term use. Minocycline, a commonly prescribed antibiotic, is another drug known to cause leukopenia. There are also reports of leukopenia caused by divalproex sodium or valproic acid (Depakote), a drug used for epilepsy (seizures), mania (with bipolar disorder) and migraine.
The anticonvulsant drug, lamotrigine, has been associated with a decrease in white blood cell count.
The FDA monograph for metronidazole states that this medication can also cause leukopenia, and the prescriber information suggests a complete blood count, including differential cell count, before and after, in particular, high-dose therapy.
Immunosuppressive drugs, such as sirolimus, mycophenolate mofetil, tacrolimus, ciclosporin, leflunomide and TNF inhibitors, have leukopenia as a known complication. Interferons used to treat multiple sclerosis, such as interferon beta-1a and interferon beta-1b, can also cause leukopenia.
Chemotherapy targets cells that grow rapidly, such as tumors, but can also affect white blood cells, because they are characterized by bone marrow as rapid growing. A common side effect of cancer treatment is neutropenia, the lowering of neutrophils (a specific type of white blood cell).
Decreased white blood cell count may be present in cases of arsenic toxicity.
A 2009 study reported results from 36 children who had received a stem cell transplant. At the time of follow-up (median time 62 months), 75% of the children were still alive.
Left shift or blood shift is an increase in the number of immature leukocytes in the peripheral blood, particularly neutrophil band cells.
Less commonly, left shift may also refer to a similar phenomenon in severe anemia, when reticulocytes and immature erythrocyte precursors appear in the peripheral circulation.
In some cancers, such as melanoma and colorectal cancer, lymphocytes can migrate into and attack the tumor. This can sometimes lead to regression of the primary tumor.
An increase in eosinophil granulocyte is known as eosinophilia.
Granulocytosis can be a feature of a number of diseases:
- Infection, especially bacterial
- Malignancy, most notably leukemia (it is the main feature of chronic myelogenous leukemia, CML)
- Autoimmune disease
Although patients can receive intensive antibiotherapy and even granulocyte transfusions from healthy donors, the only current curative therapy is the hematopoietic stem cell transplant. However, progress has been made in gene therapy, an active area of research. Both foamyviral and lentiviral vectors expressing the human ITGB2 gene under the control of different promoters have been developed and have been tested so far in preclinical LAD-I models (such as CD18-deficient mice and canine leukocyte adhesion deficiency-affected dogs).
The treatment of primary immunodeficiencies depends foremost on the nature of the abnormality. Somatic treatment of primarily genetic defects is in its infancy. Most treatment is therefore passive and palliative, and falls into two modalities: managing infections and boosting the immune system.
Reduction of exposure to pathogens may be recommended, and in many situations prophylactic antibiotics or antivirals may be advised.
In the case of humoral immune deficiency, immunoglobulin replacement therapy in the form of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) may be available.
In cases of autoimmune disorders, immunosuppression therapies like corticosteroids may be prescribed.
Regular administration of exogenous granulocyte colony-stimulating factor (filgrastim) clinically improves neutrophil counts and immune function and is the mainstay of therapy, although this may increase risk for myelofibrosis and acute myeloid leukemia in the long term.
Over 90% of SCN responds to treatment with granulocyte colony-stimulating factor (filgrastim), which has significantly improved survival.
Bone marrow transplant may be possible for Severe Combined Immune Deficiency and other severe immunodeficiences.
Virus-specific T-Lymphocytes (VST) therapy is used for patients who have received hematopoietic stem cell transplantation that has proven to be unsuccessful. It is a treatment that has been effective in preventing and treating viral infections after HSCT. VST therapy uses active donor T-cells that are isolated from alloreactive T-cells which have proven immunity against one or more viruses. Such donor T-cells often cause acute graft-versus-host disease (GVHD), a subject of ongoing investigation. VSTs have been produced primarily by ex-vivo cultures and by the expansion of T-lymphocytes after stimulation with viral antigens. This is carried out by using donor-derived antigen-presenting cells. These new methods have reduced culture time to 10–12 days by using specific cytokines from adult donors or virus-naive cord blood. This treatment is far quicker and with a substantially higher success rate than the 3–6 months it takes to carry out HSCT on a patient diagnosed with a primary immunodeficiency. T-lymphocyte therapies are still in the experimental stage; few are even in clinical trials, none have been FDA approved, and availability in clinical practice may be years or even a decade or more away.
Low white cell count may be due to acute viral infections, such as a cold or influenza. It has been associated with chemotherapy, radiation therapy, myelofibrosis, aplastic anemia (failure of white cell, red cell and platelet production), stem cell transplant, bone marrow transplant, HIV, AIDS, and steroid use.
Other causes of low white blood cell count include systemic lupus erythematosus, Hodgkin's lymphoma, some types of cancer, typhoid, malaria, tuberculosis, dengue, rickettsial infections, enlargement of the spleen, folate deficiencies, psittacosis, sepsis, Sjögren's syndrome and Lyme disease. It has also been shown to be caused by deficiency in certain minerals, such as copper and zinc.
Pseudoleukopenia can develop upon the onset of infection. The leukocytes (predominately neutrophils, responding to injury first) start migrating toward the site of infection, where they can be scanned. Their migration causes bone marrow to produce more WBCs to combat infection as well as to restore the leukocytes in circulation, but as the blood sample is taken upon the onset of infection, it contains low amount of WBCs, which is why it is termed "pseudoleukopenia".