Lymphocytopenia caused by Feline Leukemia Virus and Feline immunodeficiency virus retroviral infections is treated with Lymphocyte T-Cell Immune Modulator.

The most common cause of temporary lymphocytopenia is a recent infection, such as the common cold.

Lymphocytopenia, but not idiopathic CD4+ lymphocytopenia, is associated with corticosteroid use, infections with HIV and other viral, bacterial, and fungal agents, malnutrition, systemic lupus erythematosus, severe stress, intense or prolonged physical exercise (due to cortisol release), rheumatoid arthritis, sarcoidosis, and iatrogenic (caused by other medical treatments) conditions.

Lymphocytopenia is a frequent, temporary result from many types of chemotherapy, such as with cytotoxic agents or immunosuppressive drugs. Some malignancies that have spread to involve the bone marrow, such as leukemia or advanced Hodgkin's disease, also cause lymphocytopenia.

Another cause is infection with Influenza A virus subtype H1N1 (and other subtypes of the Influenza A virus) and is then often associated with Monocytosis; H1N1 was responsible for the Spanish flu, the 2009 flu pandemic and in 2016 for the Influenza-epidemic in Brazil.

Large doses of radiation, such as those involved with nuclear accidents or medical whole body radiation, may cause lymphocytopenia.

Monocytosis often occurs during chronic inflammation. Diseases that produce such a chronic inflammatory state:

- Infections: tuberculosis, brucellosis, listeriosis, subacute bacterial endocarditis, syphilis, and other viral infections and many protozoal and rickettsial infections (e.g. kala azar, malaria, Rocky Mountain spotted fever).

- Blood and immune causes: chronic neutropenia and myeloproliferative disorders.

- Autoimmune diseases and vasculitis: systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease.

- Malignancies: Hodgkin's disease and certain leukaemias, such as chronic myelomonocytic leukaemia (CMML) and monocytic leukemia.

- Recovery phase of neutropenia or an acute infection.

- Obesity (cf. Nagareddy et al. (2014), Cell Metabolism, Vol. 19, pp 821-835)

- Miscellaneous causes: sarcoidosis and lipid storage disease.

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

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.

Neutropenia can be acquired or intrinsic. A decrease in levels of neutrophils on lab tests is due to either decreased production of neutrophils or increased removal from the blood. The following list of causes is not complete.

- Medications - chemotherapy, sulfas or other antibiotics, phenothiazenes, benzodiazepines, antithyroids, anticonvulsants, quinine, quinidine, indomethacin, procainamide, thiazides

- Radiation

- Toxins - alcohol, benzenes

- Intrinsic disorders - Fanconi's, Kostmann's, cyclic neutropenia, Chédiak–Higashi

- Immune dysfunction - disorders of collagen, AIDS, rheumatoid arthritis

- Blood cell dysfunction - megaloblastic anemia, myelodysplasia, marrow failure, marrow replacement, acute leukemia

- Any major infection

- Miscellaneous - starvation, hypersplenism

Symptoms of neutropenia are associated with the underlying cause of the decrease in neutrophils. For example, the most common cause of acquired neutropenia is drug-induced, so an individual may have symptoms of medication overdose or toxicity.

Treatment is also aimed at the underlying cause of the neutropenia. One severe consequence of neutropenia is that it can increase the risk of infection.

Leukocytosis is very common in acutely ill patients. It occurs in response to a wide variety of conditions, including viral, bacterial, fungal, or parasitic infection, cancer, hemorrhage, and exposure to certain medications or chemicals including steroids.

For lung diseases such as pneumonia and tuberculosis, WBC count is very important for the diagnosis of the disease, as leukocytosis is usually present.

The mechanism that causes leukocytosis can be of several forms: an increased release of leukocytes from bone marrow storage pools, decreased margination of leukocytes onto vessel walls, decreased extravasation of leukocytes from the vessels into tissues, or an increase in number of precursor cells in the marrow.

Certain medications, including corticosteroids, lithium and beta agonists, may cause leukocytosis.

Leukocytosis can be subcategorized by the type of white blood cell that is increased in number. Leukocytosis in which neutrophils are elevated is neutrophilia; leukocytosis in which lymphocyte count is elevated is lymphocytosis; leukocytosis in which monocyte count is elevated is monocytosis; and leukocytosis in which eosinophil count is elevated is eosinophilia.

An extreme form of leukocytosis, in which the WBC count exceeds 100,000/µL, is leukostasis. In this form there are so many WBCs that clumps of them block blood flow. This leads to ischemic problems including transient ischemic attack and stroke.

Monocytosis is the state of excess monocytes in the peripheral blood. It may be indicative of various disease states.

Examples of processes that can increase a monocyte count include:

- chronic inflammation

- stress response

- Cushing's syndrome (hyperadrenocorticism)

- immune-mediated disease

- granulomatous disease

- atherosclerosis

- necrosis

- red blood cell regeneration

- viral fever

- sarcoidosis

A high count of CD14+CD16++ monocytes is found in severe infection (sepsis)

In the field of atherosclerosis high numbers of the CD14++CD16+ intermediate monocytes were shown to be predictive of cardiovascular events in at risk populations.

Monocytes are a type of "leukocyte", or white blood cell. They are the largest type of leukocyte and can differentiate into macrophages and myeloid lineage dendritic cells. As a part of the vertebrate innate immune system monocytes also influence the process of adaptive immunity. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.

Most patients with "ETV6-ACSL6"-related disease present with findings similar to eosinophilia, hypereosinophila, or chronic eosinophilic leukemia; at least 4 cases presented with eosinophilia plus findings of the red blood cell neoplasm, polycythemia vera; three cases resembled acute myelogenous leukemia; and one case presented with findings of a combined Myelodysplastic syndrome/myeloproliferative neoplasm. Best treatments for "ETV6-ACSL6"-related disease are unclear. Patients with the polycythemia vera form of the disease have been treated by reducing the circulating red blood cell load by phlebotomy or suppressing red blood cell formation using hydroxyurea. Individual case studies report that "ETV6-ACSL6"-associated disease is insensitive to tyrosine kinase inhibitors. Best treatment currently available, therefore, may involve chemotherapy and bone marrow transplantion.

The incidence and prevalence of hyperleukocytosis and leukostasis varies depending on the form of leukemia. Hyperleukocytosis is common in chronic myelogenous leukemia and chronic lymphocytic leukemia but leukostasis rarely occurs. Similarly, the incidence of hyperleukocytosis in people with acute lymphoblastic leukemia is between 10-30% but rarely does this progress to symptomatic leukostasis. The incidence of hyperleukocytosis in acute myeloid leukemia (AML) ranges between 5-20% but leukostasis is less common than hyperleukocytosis in this population; leukostasis tends to occur more often in people with AML with monocytic features.

Serious complications are uncommon, occurring in less than 5% of cases:

- CNS complications include meningitis, encephalitis, hemiplegia, Guillain–Barré syndrome, and transverse myelitis. Prior infectious mononucleiosis has been linked to the development of multiple sclerosis (MS).

- Hematologic: Hemolytic anemia (direct Coombs test is positive) and various cytopenias, and bleeding (caused by thrombocytopenia) can occur.

- Mild jaundice

- Hepatitis with the Epstein–Barr virus is rare.

- Upper airway obstruction from tonsillar hypertrophy is rare.

- Fulminant disease course of immunocompromised patients is rare.

- Splenic rupture is rare.

- Myocarditis and pericarditis are rare.

- Postural orthostatic tachycardia syndrome

- Chronic fatigue syndrome

- Cancers associated with the Epstein-Barr virus include: Burkitt's lymphoma, Hodgkin's lymphoma and lymphomas in general as well as nasopharyngeal and gastric carcinoma.

Once the acute symptoms of an initial infection disappear, they often do not return. But once infected, the patient carries the virus for the rest of his or her life. The virus typically lives dormantly in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the patient is already carrying the virus dormantly. Periodically, the virus can reactivate, during which time the patient is again infectious, but usually without any symptoms of illness. Usually, a patient has few, if any, further symptoms or problems from the latent B lymphocyte infection. However, in susceptible hosts under the appropriate environmental stressors, the virus can reactivate and cause vague physical symptoms (or may be subclinical), and during this phase the virus can spread to others.

Lymphocyte-variant hypereosinophilia is a rare disease in which eosinophilia is caused by aberrant T cell lymphocytes which secrete cytokines (e.g. interleukin-5) that stimulate the proliferation of eosinophil precursor cells. The disease, which occasionally proceeds to a malignant lymphocytic phase, clearly reflects a clonal disturbance in lymphocytes, not eosinophils, and therefore is not a clonal hypereosinophilia. Similar non-clonal eosinophilia due to eosinophil precursor cell stimulation by clonal malignant cells is sometimes seen in cases of Hodgkin disease, B-cell lymphoma, T-cell lymphomas, T cell leukemias, and Langerhans cell histiocytosis. Other hematological diseases are associated with eosinophilia but regarded as clonal eosinophilia associated with a more important clonal malignancy in another cell type. For example, eosinophilia occurs in 20% to 30% of patients with systemic mastocytosis. Also referred to as SM-eo (systemic mastocytosis with eosinophilia) or SM-SEL (systemic mastocytosis with chronic eosinophilic leukemia), this disease's clonal eosinophils bear the same driving mutation, D816V in the"KIT" gene, as the clonal mast cells.

Leukostasis is a high-risk condition and can lead to significant complications resulting from occlusion of blood vessels including transient ischemic attacks and strokes.

Splenomegaly is a common symptom of infectious mononucleosis and health care providers may consider using abdominal ultrasonography to get insight into the enlargement of a person's spleen. However, because spleen size varies greatly, ultrasonography is not a valid technique for assessing spleen enlargement and should not be used in typical circumstances or to make routine decisions about fitness for playing sports.

JMML accounts for 1-2% of childhood leukemias each year; in the United States, an estimated 25-50 new cases are diagnosed each year, which also equates to about 3 cases per million children. There is no known environmental cause for JMML. Since about 10% of patients are diagnosed before 3 months of age, it is thought that JMML is a congenital condition in these infants

There have been few individual epidemiological studies of CMML, due to the difficulty in the disease classification. CMML has an estimated incidence of less than 1 per 100,000 persons per year.

The median age of diagnosis is 65–75. CMML has a propensity for males rather than females, at a ratio of 1.5–3:1.

RAS-associated autoimmune leukoproliferative disorder (RALD) is a rare genetic disorder of the immune system. RALD is characterized by lymphadenopathy, splenomegaly, autoimmunity, and elevation in granulocytes and monocytes. It shares many features with autoimmune lymphoproliferative syndrome and is caused by somatic mutations in NRAS or KRAS. This was first described by investigators João Oliveira and Michael Lenardo from the National Institutes of Health.

Clinically, RALD is characterized by splenomegaly, a relatively mild degree of peripheral lymphadenopathy, and autoimmunity. The autoimmune phenotype can present in childhood or adulthood and primarily includes autoimmune hemolytic anemia, ITP, and neutropenia. Some patients have a history of recurrent respiratory tract infections. It is unclear if increased risk for malignancy is part of RALD.

Importantly, however, the clinical and laboratory phenotype resembles juvenile myelomonocytic leukemia. The high fatality rate of this childhood blood cancer puts it in sharp contrast when compared to the relatively benign and chronic course of RALD. Approximately 15-30% of patients diagnosed with JMML have somatic, activating RAS mutations. However, due to the difficulty in distinguishing JMML from RALD, it is possible a subset of patients treated for JMML actually have RALD and could therefore avoid the aggressive JMML treatment. This distinction is under investigation.

Although the cause of CMML is unknown, environmental carcinogens, ionising radiation and cytotoxic agents may have a role in causing disease. Approximately one third of cases of MDS with a monocyte count of >10% and <1x10/L will progress to CMML.

Prognosis refers to how well a patient is expected to respond to treatment based on their individual characteristics at time of diagnosis. In JMML, three characteristic areas have been identified as significant in the prognosis of patients:

Without treatment, the survival [5 years?] of children with JMML is approximately 5%. Only Hematopoietic Stem Cell Transplantation (HSCT), commonly referred to as a bone marrow or (umbilical) cord blood transplant, has been shown to be successful in curing a child of JMML. With HSCT, recent research studies have found the survival rate to be approximately 50%. Relapse is a significant risk after HSCT for children with JMML. It is the greatest cause of death in JMML children who have had stem cell transplants. Relapse rate has been recorded as high as 50%. Many children have been brought into remission after a second stem cell transplant.

The exact cause of sarcoidosis is not known. The current working hypothesis is, in genetically susceptible individuals, sarcoidosis is caused through alteration to the immune response after exposure to an environmental, occupational, or infectious agent. Some cases may be caused by treatment with TNF inhibitors like etanercept.

The heritability of sarcoidosis varies according to ethnicity. About 20% of African Americans with sarcoidosis have a family member with the condition, whereas the same figure for European Americans is about 5%. Additionally, in African Americans, who seem to experience more severe and chronic disease, siblings and parents of sarcoidosis cases have about a 2.5-fold increased risk for developing the disease. Investigations of genetic susceptibility yielded many candidate genes, but only few were confirmed by further investigations and no reliable genetic markers are known. Currently, the most interesting candidate gene is "BTNL2"; several "HLA-DR" risk alleles are also being investigated. In persistent sarcoidosis, the HLA haplotype "HLA-B7-DR15" are either cooperating in disease or another gene between these two loci is associated. In nonpersistent disease, there is a strong genetic association with HLA DR3-DQ2. Cardiac sarcoid has been connected to TNFA variants.