Signs and symptoms of neutropenia include fever, painful swallowing, gingival pain, skin abscesses, and otitis. These symptoms may exist because individuals with neutropenia often have infection

Children may show signs of irritability, and poor feeding. Additionally, hypotension has also been observed in individuals who suffer from this condition

Agranulocytosis may be asymptomatic, or may clinically present with sudden fever, rigors and sore throat. Infection of any organ may be rapidly progressive (e.g., pneumonia, urinary tract infection). Septicemia may also progress rapidly.

Neutropenia or neutropaenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood. Patients with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening (neutropenic sepsis).

Neutropenia can be acute (temporary) or chronic (long lasting). The term is sometimes used interchangeably with "leukopenia" ("deficit in the number of white blood cells").

Febrile neutropenia can develop in any form of neutropenia, but is most generally recognized as a complication of chemotherapy when it is myelosuppressive (suppresses the bone marrow from producing blood cells).

The term "agranulocytosis" derives from the Greek: "a", meaning without; granulocyte, a particular kind of white blood cell (containing granules in its cytoplasm); and "osis", meaning condition [esp. disorder]. Consequently, agranulocytosis is sometimes described as "no granulocytes", but a total absence is not required for diagnosis.

However, "-osis" is commonly used in blood disorders to imply cell proliferation (such as in "leukocytosis"), while "-penia" to imply reduced cell numbers (as in "leukopenia"); for these reasons, granulopenia is a more etymologically consistent term, and as such, is sometimes preferred to "agranulocytosis" (which can be misinterpreted as "agranulocyt-osis", meaning proliferation of agranulocytes (i.e. lymphocytes and monocytes). Despite this, "agranulocytosis" remains the most widely used term for the condition.

The terms agranulocytosis, granulocytopenia and neutropenia are sometimes used interchangeably. Agranulocytosis implies a more severe deficiency than granulocytopenia. Neutropenia indicates a deficiency of neutrophils (the most common granulocyte cell) only.

To be precise, neutropenia is the term normally used to describe absolute neutrophil counts (ANCs) of less than 500 cells per microlitre, whereas agranulocytosis is reserved for cases with ANCs of less than 100 cells per microlitre.

The following terms can be used to specify the type of granulocyte referenced:

- Inadequate numbers of neutrophils: neutropenia (most common)

- Inadequate numbers of eosinophils: eosinopenia (uncommon)

- Inadequate numbers of basophils: basopenia (very rare)

In a general sense the pathogenesis of neutropenia can be divided into two categories;

- Inadequate or ineffective formation of granulocytes. This can be due to bone marrow failure such that occurs in aplastic anaemia, several leukaemias and chemotherapeutic agents. There can also be isolated neutropenias where only differentiated granulocyte precursors are affected as in the case of neoplastic proliferation of cytotoxic T cells or NK cells

- Accelerated destruction of neutrophils. Immune-mediated reactions to neutrophils which can be caused by drugs. An enlarged spleen can lead to splenic sequestration and accelerated removal of neutrophils. Utilization of neutrophils can occur in infections

Monocytopenia is a form of leukopenia associated with a deficiency of monocytes. The causes of monocytopenia include: acute infections, stress, treatment with glucocorticoids, aplastic anemia, hairy cell leukemia, acute myeloid leukemia, treatment with myelotoxic drugs and genetic syndromes, as for example MonoMAC syndrome.

It has been proposed as a measure to predict neutropenia, though some research indicates that it is less effective than lymphopenia.

Cyclic neutropenia is a disorder that causes frequent infections and other health problems in affected individuals. People with this condition have recurrent episodes of neutropenia during which there is a shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection. The episodes of neutropenia are apparent at birth or soon afterward. For most affected individuals, neutropenia recurs every 21 days and lasts about 3 to 5 days.

Neutropenia makes it more difficult for the body to fight off pathogens such as bacteria and viruses, so people with cyclic neutropenia typically develop recurrent infections of the sinuses, respiratory tract, and skin. Additionally, people with this condition often develop open sores (ulcers) in the mouth and colon, inflammation of the throat (pharyngitis) and gums (gingivitis), recurrent fever, or abdominal pain. People with cyclic neutropenia have these health problems only during episodes of neutropenia. At times when their neutrophil levels are normal, they are not at an increased risk of infection and inflammation.

Autoimmune neutropenia is a form of neutropenia which is most common in infants and young children where the body identifies the neutrophils as enemies and makes antibody to destroy them.

Primary autoimmune neutropenia (AIN) is an autoimmune disease first reported in 1975 that primarily occurs in infancy. In autoimmune neutropenia, the immune system produces autoantibodies directed against the neutrophilic protein antigens in white blood cells known as granulocytic neutrophils (granulocytes, segmented neutrophils, segs, polysegmented neutrophils, polys). These antibodies destroy granulocytic neutrophils. Consequently, patients with autoimmune neutropenia have low levels of granulocytic neutrophilic white blood cells causing a condition of neutropenia. Neutropenia causes an increased risk of infection from organisms that the body could normally fight easily.

Who is Affected?

Primary autoimmune neutropenia has been reported as early as the second month of life although most cases are diagnosed in children between 5 and 15 months of age. Girls have a slightly higher risk of developing AIN than boys. In neutropenia discovered at birth or shortly after birth, a diagnosis of allo-immune neutropenia (from maternal white blood cell antibodies passively transferred to the infant) is more likely.

Neutropenia

In infants neutropenia is defined by absolute neutrophil counts less than 1000/uL. After the first year of life neutropenia is defined by absolute counts less than 1500/uL. Neutropenia may be primary in which it is the only blood abnormality seen. In secondary neutropenia, other primary conditions occur, including other autoimmune diseases, infections, and malignancies. Neutropenia is considered chronic when it persists for more than 6 months.

Symptoms and Disease Course

Neutropenia, which may be discovered on routine blood tests, typically causes benign infections even when the condition is severe. Ear infections (otitis media) are the most common infection seen in autoimmune neutropenia and typically infection responds to antibiotic treatment alone. Infections associated with primary AIN are usually mild and limited, including skin infections such as impetigo, gastroenteritis, upper respiratory tract infections, and ear infections. Rarely, cellulitis and abscesses may occur.

Studies of children studied for up to six years showed that most cases of autoimmune neutropenia resolved spontaneously after a median of 17 months. In 80 percent of patients, neutropenia persisted for 7 to 24 months.

Diagnosis

Patients with autoimmune neutropenia are diagnosed on the basis of blood tests showing neutropenia and the presence of granulocyte-specific antibodies. In some cases, tests for granulocyte-specific antibodies need to be repeated several times before a positive result is seen. Bone marrow aspiration, if performed, is typically normal or it can show increased cell production with a variably diminished number of segmented granulocytes.

s association with prior parvovirus B19 has been made, but this hasn’t been confirmed. Similar to the platelet deficiency idiopathic thrombocytopenic purpura, vaccines are suspected of triggering this disorder.

Treatment

Treatment consists of corticosteroids to reduce autoantibody production, antibiotics to prevent infection and granulocyte colony-stimulating factor (G-CSF) to temporarily increase neutrophil counts. In cases of severe infection or the need for surgery, intravenous immunoglobulin therapy may be used.

The disease occurs much more in males than females (due to the X-linked recessive pattern of inheritance) and is estimated to occur in between 1 and 10 males per million. The first signs of WAS are usually petechiae and bruising, resulting from a low platelet count. Spontaneous nose bleeds and bloody diarrhea are common. Eczema develops within the first month of life. Recurrent bacterial infections develop by three months. Enlargement of the spleen is not an uncommon finding. The majority of WAS children develop at least one autoimmune disorder, and cancers (mainly lymphoma and leukemia) develop in up to a third of patients. Immunoglobulin M (IgM) levels are reduced, IgA and IgE are elevated, and IgG levels can be normal, reduced, or elevated. In addition to low blood platelet counts (i.e. thrombocytopenia), ~30% of afflicted individuals exhibit eosinophilia, i.e. high blood eosinophil counts.

Leukopenia can be identified with a complete blood count.

Below are blood reference ranges for various types leucocytes/WBCs. The 2.5 percentile (right limits in intervals in image, showing 95% prediction intervals) is a common limit for defining leukocytosis.

Myelokathexis is a congenital disorder of the white blood cells that causes severe, chronic leukopenia (a reduction of circulating white blood cells) and neutropenia (a reduction of neutrophil granulocytes). The disorder is believed to be inherited in an autosomal dominant manner. Myelokathexis refers to retention (kathexis) of neutrophils in the bone marrow (myelo). The disorder shows prominent neutrophil morphologic abnormalities.

Myelokathexis is amongst the diseases treated with bone marrow transplantation and cord blood stem cells.

WHIM syndrome is a very rare variant of severe congenital neutropenia that presents with warts, hypogammaglobunemia, infections, and myelokathexis. A gain in function mutation resulting in a truncated form of CXCR4 is believe to be its cause.

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".

Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954. The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may present similar but less severe symptoms and are caused by mutations of the same gene.

Febrile neutropenia is the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes (a type of white blood cell) in the blood. The term neutropenic sepsis is also applied, although it tends to be reserved for patients who are less well. In 50% of cases, an infection is detectable; bacteremia (bacteria in the bloodstream) is present in approximately 20% of all patients with this condition.

X-linked thrombocytopenia is typically diagnosed in infancy. The disease presents as a bleeding disorder with easy bruising, mucosal bleeding, such as nosebleeds, and mild to severe anemia. Anemia is a condition in which there is an insufficient number of red blood cells to carry adequate levels of oxygen to the body’s tissues. X-linked thrombocytopenia is considered to be the milder phenotype of the "WAS"-related disorders. As age increases, the severity of symptoms tends to decrease. However, individuals with X-linked thrombocytopenia have an increased risk for life-threatening brain hemorrhages and spontaneous bleeding.

This syndrome is characterized by an increased susceptibility to disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis, and molds. There is profound monocytopenia, B lymphocytopenia and NK lymphocytopenia. Patients have an increased chance of developing malignancies, including: myelodysplasia/leukemia vulvar carcinoma, metastatic melanoma, cervical carcinoma, Bowen disease of the vulva, and multiple Epstein-Barr virus(+) leiomyosarcoma. Patients may also develop pulmonary alveolar proteinosis without mutations in the granulocyte-macrophage colony-stimulating factor receptor or anti-granulocyte-macrophage colony-stimulating factor autoantibodies. Last, patients may develop autoimmune phenomena, including lupus like syndromes, primary biliary cirrhosis or aggressive multiple sclerosis.

Of the 26, now 28, patients probably afflicted by this syndrome, 48% died of causes ranging from cancer to myelodysplasia with a mean age at death of 34.7 years and median age of 36.5 years.

Cyclic neutropenia (or cyclical neutropenia) is a form of neutropenia, a white blood cell deficiency, that tends to occur every three weeks and lasts three to six days at a time due to changing rates of cell production by the bone marrow.

Cyclic neutropenia is the result of autosomal dominantly inherited mutations in ELA2, the gene encoding neutrophil elastase,

and is estimated to occur in 1 in 1 million individuals worldwide. Treatment includes G-CSF and usually improves after puberty.

Kostmann syndrome is a group of diseases that affect myelopoiesis, causing a congenital form of neutropenia (severe congenital neutropenia [SCN]), usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections.

Most cases of SCN respond to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count and decreases the severity and frequency of infections. Although this treatment has significantly improved survival, people with SCN are at risk of long-term complications such as hematopoietic clonal disorders (myelodysplastic syndrome, acute myeloid leukemia).

Kostmann disease (SCN3), the initial subtype recognized, was clinically described in 1956. This type has an autosomal recessive inheritance pattern, whereas the most common subtype of Kostmann syndrome, SCN1, shows autosomal dominant inheritance.

Infants with SCN have frequent infections: 50% have a significant infection within 1 month, most others by 6 months. Their etiology is usually bacterial, especially staphylococcal, and they commonly involve abscesses, both cutaneous and of internal organs, pneumonia, mastoiditis (inflammation of the mastoid process), and sepsis. All of these are life-threatening for infants.

Signs and symptoms are nonspecific and generally related to the blood cytopenias:

- Anemia (low RBC count or reduced hemoglobin) —chronic tiredness, shortness of breath, chilled sensation, sometimes chest pain

- Neutropenia (low neutrophil count) — increased susceptibility to infection

- Thrombocytopenia (low platelet count) — increased susceptibility to bleeding and ecchymosis (bruising), as well as subcutaneous hemorrhaging resulting in purpura or petechiae

Many individuals are asymptomatic, and blood cytopenia or other problems are identified as a part of a routine blood count:

- Neutropenia, anemia, and thrombocytopenia

- Splenomegaly or rarely hepatomegaly

- Abnormal granules in cells, abnormal nuclear shape and size

- Chromosome abnormality, including chromosomal translocations and abnormal chromosome number

Although some risk exists for developing acute myelogenous leukemia, about 50% of deaths occur as a result of bleeding or infection. However, leukemia that occurs as a result of myelodysplasia is notoriously resistant to treatment.

Anemia dominates the early course. Most symptomatic patients complain of the gradual onset of fatigue and weakness, dyspnea, and pallor, but at least half the patients are asymptomatic and their MDS is discovered only incidentally on routine blood counts. Previous chemotherapy or radiation exposure is an important fact in the person's medical history. Fever and weight loss should point to a myeloproliferative rather than myelodysplastic process.

MonoMAC is a rare autosomal dominant syndrome associated with monocytopenia, B and NK cell lymphopenia and mycobacterial, fungal and viral infections. It was first described by Vihn and colleagues in 2010 and is associated with myelodysplasia, cytogenetic abnormalities, pulmonary alveolar proteinosis and myeloid leukemias. Multiple mutations in the GATA2 are considered to be responsible for this syndrome.

X-linked thrombocytopenia, also referred to as XLT or thrombocytopenia 1, is an inherited clotting disorder that primarily affects males. It is a "WAS"-related disorder, meaning it is caused by a mutation in the Wiskott-Aldrich Syndrome ("WAS") gene, which is located on the short arm of the X chromosome. "WAS"-related disorders include Wiskott-Aldrich syndrome, XLT, and X-linked congenital neutropenia (XLN). Of the "WAS"-related disorders, X-linked thrombocytopenia is considered to be the milder phenotype. Between 1 and 10 per million males worldwide are affected with this disorder. Females may be affected with this disorder but this is very rare since females have two X chromosomes and are therefore typically carriers of the mutation.

WHIM Syndrome (or Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis syndrome) is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia.

Monocytosis is an increase in the number of monocytes circulating in the blood. Monocytes are white blood cells that give rise to macrophages and dendritic cells in the immune system.

In humans, 950/μL is regarded as at the upper limit of normal; monocyte counts above this level are regarded as monocytosis.

Monocytosis has sometimes been called mononucleosis, but that name is usually reserved specifically for infectious mononucleosis.

Myelodysplastic syndromes (MDS) are a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells. Early on there are typically no symptoms. Later symptoms may include feeling tired, shortness of breath, easy bleeding, or frequent infections. Some types may develop into acute myeloid leukemia.

Risk factors include previous chemotherapy or radiation therapy, exposure to certain chemicals such as tobacco smoke, pesticides, and benzene, and exposure to heavy metals such as mercury or lead. Problems with blood cell formation result in some combination of low red blood cells, low platelets, and low white blood cells. Some types have an increase in immature blood cells, called blasts, in the bone marrow or blood. The types of MDS are based on specific changes in the blood cells and bone marrow.

Treatments may include supportive care, drug therapy, and stem cell transplantation. Supportive care may include blood transfusions, medications to increase the making of red blood cells, and antibiotics. Drug therapy may include the medication lenalidomide, antithymocyte globulin, and azacitidine. Certain people can be cured with chemotherapy followed by a stem-cell transplant from a donor.

About seven per 100,000 people are affected with about four per 100,000 people newly acquiring the condition each year. The typical age of onset is 70 years. The outlook depends on the type of cells affected, the number of blasts in the bone marrow or blood, and the changes present in the chromosomes of the affected cells. The typical survival rate following diagnosis is 2.5 years. The conditions were first recognized in the early 1900s. The current name came into use in 1976.