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Benign White Blood Cell Disorders: Leukocytosis (high white blood cell count)

Leukocytosis is an increased number of leukocytes(leukocyte count), or white blood cells (WBCs) above the normal range for age and sex, in the blood. For adults this is > 11.0 x109/L leukocytes. The WBCs are the blood cells responsible for the immune response, the fighting of infection. There are many different kinds of WBCs, each with their own particular function. WBCs are produced in the bone marrow, circulate for a time in the blood, and leave the blood to perform their function in the tissues. WBC levels may increase due to increased marrow production or decreased exit from the blood to the tissues.

An increase in the WBC count is a typical response to noxious stimuli and is usually part of an inflammatory reaction. A leukocytosis is frequently accompanied by cytologic abnormalities, such as toxic granulation or Dohle bodies. Although all or individual types of leukocytes (neutrophils, lymphocytes, etc.)

Causes of a high white blood cell count (leukocytosis) include:

  • Infection
  • Use of certain medications, such as corticosteroids, antibiotics or anti-seizure drugs
  • Severe physical or emotional stress
  • Chronic bone marrow diseases such as a myeloproliferative disorder
  • Acute or chronic leukemia
  • Tissue damage, such as from burns





Neutrophils are WBCs that move from the blood into the cells to kill invading bacteria and fungi. If neutrophil levels become too high, neutrophilia results. Neutrophilia is the most common form of leukocytosis. In a bacterial or fungal infection, more neutrophils are produced to fight the disease. However, there are many other causes of neutrophilia.

Causes - Neutrophilia

Among the causes of neutrophilia are infections (i.e. bacterial or fungal infections or tuberculosis), inflammatory diseases such as rheumatoid arthritis, and loss of blood cells through bleeding or hemolysis (destruction of blood cells). Elevations in hormones (such as adrenocorticosteroids and epinephrine) or steroid medications such as Prednisone may also increase neutrophil production.

Neutrophilia may be due to a number of acute and chronic causes: infection, inflammation, necrosis, physical agents, emotional stimuli, drugs, toxins, neoplasia, metabolic, hormonal, and endocrine disturbances, and hematologic abnormalities.

In response to inflammation or other stimuli, neutrophils move from the marginating or storage pool into the circulating peripheral blood. Next bone marow reserves are shifted into the peripheral blood and finally marrow production is increased.

Immature neutrophils (bands, metamyelocytes, myelocytes, and occasionally promyelocytes) are released into the peripheral blood. This premature release of not yet fully mature neutrophils is called a myeloid "left shift".

Normal mature neutrophils contain small amounts of leukocyte alkaline phosphatase (LAP) in primary granules. The peripheral blood LAP is elevated during leukocytosis because of the "left shift".

Minor causes of leukocytosis include:

Pseudoneutrophilia may result in response to acute stress (exercise, epinephrine,anesthesia, etc.) There is no increase in the total number of neutrophils, only a shift from the marginal storage pool to the circulating blood.

Asplenia can result in a moderate leukocytosis as the normal spleen holds a large part of the marginating pool of leukocytes.

Corticosteroids may stimulate the release of neutrophils from the marrow and slow or prevent the egress of neutrophils from the circulation.

Symptoms of neutrophilia

Symptoms of neutrophilia are usually the result of the underlying problem, such as signs of infection, bleeding, or bone marrow disorder. The disorder is diagnosed by patient history, physical examination for symptoms, and laboratory testing. The goal of diagnosis is to detect elevated neutrophil levels and to determine the cause of this problem. Treatment focuses upon addressing the underlying disorder or disease.


Related Conditions of leukocytosis

Three conditions related to leukocytosis are leukostasis, and leukemoid and leukoerythroblastic reactions.

Leukostasis results from sludging of high numbers of leukocytes in small vessels, particularly the brain, lungs, and kidneys. Death may occur due to impaired blood flow or enormous metabolic requirements of large numbers of leukocytes. Leukostasis is most common with myeloid leukemia (blast counts >50.0 x109/L) but are rare in chronic lymphocytic leukemia (CLL) with any white count. This may be due to the large size of the myeloid blasts compared to CLL cells or may relate to different expression of intercellular adhesion molecules.

Leukemoid reactions are characterized by blasts, promyelocytes, myelocytes, and metamyelocytes in the peripheral blood. Leukemoid reactions may be secondary to benign or malignant conditions. The WBC count is often in a range of 50.0-100.0 x10 9/L.

A Leukoerythroblastic reaction is similar to a leukomoid reaction with the addition of nucleated red blood cells. A leukoerythroblastic picture indicates severe disruption of the marrow and is common in myelofibrosis (primary or secondary). Leukoerythroblastic reactions suggest possible extramedullary hemtopoiesis and is often secondary to metastatic cancer.

In infants a leukoerythroblastic reaction suggests severe hemolytic anemia, such as erythroblastosis fetalis (shown below).

Another disease, osteopetrosis is a rare childhood disorder of bone in which abnormal osteoclasts are unable to resorb bone. Thus bone unable to be remodelled, replaces hematopoietic marrow space, leading to extramedullary hematopoiesis and spillage of hematopoietic elements into the peripheral blood.

In addition to neutrophilia one may encounter specific increases in the number of lymphocytes, eosinophils, basophils, and monocytes in the peripheral blood.

Of these, most common is lymphocytosis ( lymphocytes > 4.0 x109/L in adults and > 9.0 x109/L in children ).

One must always consider the absolute lymphocyte count to determine if a lymphocytosis is present.

Lymphocytoses occur most frequently during viral infections and only rarely in bacterial infection except pertussis.

Pertussis or whooping cough is frequently accompanied by a lymphocytosis ( usually 20.0-30.0 x109/L, but may exceed 50.0 x109/L ) of small mature appearing lymphocytes.

Toxoplasmosis may cause an lymphocytosis similar to infectious mononucleosis with atypical lymphocytes, fever, and lymphadenopathy.

The chronic infections brucellosis and syphilis may occassionally cause an atypical lymphocytosis.

Infectious mononucleosis - The disease is generally self limited and is caused by an Epstein-Barr virus infection of B lymphocytes. During the second week of illness, a proliferation of activated cyotoxic/suppressor T cells occurs.

It is these CD8 positive T cytotoxic/suppressor cells that we see in the PB and that kill the infected B cells. The atypical lymphocytes are large and reactive with abundant basophilic cytoplasm. Some may appear almost blast-like. These changes are not unique to IM, but can be seen in other viral infections.

Infectious mononucleosis is most common in adolescents and young adults.Patients present with fever, sore throat, and lymphadenopathy (often cervical). Splenomegaly is common. CMV occassionally causes a lymphocytosis with symptoms similar to IM and may follow blood transfusions.

Other viral causes of lymphocytosis include infectious lymphocytosis and HTLV-1 related transient lymphocytosis.

Infectious lymphocytosis is characterized by a lymphocytosis of small lymphocytes, generally 20.0-50.0 x109/L, but occasionlly over 100.0 x109/L. This is mainly a disease of children and is benign. It may be related to coxsackievirus A or B6, echovirus, and adenovirus 12. There is almost never splenomegaly or lymphadenopathy.

HTLV-1 may produce a transient lymphocytosis (usually < 20.0 x109/L) with fever,rash, and little lymphadenopathy. Most patients recover; however, some develop adult T cell leukemia.


Other forms of leukocytosis


Monocytosis (monocytes > 1.0 x109/L) in adults occurs in a number of disorders, most frequently in the recovery phase of infection, but may be seen in a variety of neoplastic lesions especially myeloproliferative disorders. Monocytosis may result from viral, fungal, rickettsial, and protozoal infections.

Phagocytosis of erythrocytes, leukocytes, and platelets by monocytes and histiocytes is seen in the "hemophagocytic syndrome" which is associated with viral or bacterial infections and T cell malignant lymphoma.

Monocytes, like neutrophils, destroy bacteria and fungi in the cells. When monocyte levels in the blood become elevated, monocytosis results. Infections which may cause monocytosis include bacterial infections , protozoal infections such as malaria, rickettsial infections, and tuberculosis. In addition, diseases (such as ulcerative colitis, regional enteritis, sarcoidosis, and connective tissue disorders) and cancer (especially lymphomas and leukemias) may cause monocytosis. Diagnosis and treatment involve finding the underlying cause and, if possible, addressing it.

Eosinophilia and Basophilia

Eosinophils and basophils are WBCs involved in allergic reactions. When these cells increase in the body, eosinophilia and basophilia result. Common causes of eosinophilia include allergic reactions, skin disorders, parasitic infections, myeloproliferative disorders (leukemia, polycythemia vera, myelofibrosis), and other cancers. Basophilia is less common and is usually a symptom of myeloproliferative disorders or hyperthyroidism. The disorders are diagnosed by patient history, physical examination, and laboratory testing. Treatment attempts to address the underlying problem. For allergic reactions, antihistamines may be used to relieve allergic symptoms.

Eosinophilia ( > 0.35 X 109/L ) is associated with many forms of immunologic damage and can, interestingly, inactivate IgE mediated reactions (immediate hypersensitivity).

  • allergic disorders -asthma, seasonal rhinitis, eczema, atopic dermatosis, pemphigus and dermatitis herpetiformis.
  • parasitic infections - trichinosis, tapeworm, roundworm, schistosomiasis.MBP (major basic protein) released from the eosinophilic granules coats the Schistosoma organism prior to antibody-complement independent killing.
  • other infections - scarlet fever, TB, leprosy
  • Loeffler's syndrome
  • PIE (pulmonary infiltration with eosinophilia)
  • tropical pulmonary eosinophilia
  • drug induced - sulfonamides, PCN, digitalis, nitrofurantoin
  • neoplastic - CML, tumors, (particularly involving serous linings, occasionally Hodgkin's disease).

When large numbers of eosinophils are present the crytalloid material may form Charot-Leyden crystals.


Basophilia ( > 0.2 X 109/L ) is seen in allerigic reactions and is common in chronic myelocytic leukemia. Increased basophils are associated with polycythemia vera and extramedullary hematopoiesis. Basophilia is also reported in hypothyroidism.


The lymphocytes are a group of cells that fight viral and bacterial infections and other foreign material that may enter the body. Each type plays a specific role in immunity. In lymphocytosis, the level of lymphocytes in the blood increases. Lymphocytosis may result from most bacterial infections, infectious mononucleosis, or cancers such as leukemia or non-Hodgkin’s lymphoma. Symptoms include enlarged spleen and lymph nodes and the symptoms of the underlying infection or disease. Diagnosis and treatment involve patient history, physical examination, laboratory testing to identity cause, and treatment of underlying cause.

The Leukemoid Blood Picture

Leukemoid blood picture refers to an increased number of leukocytes, or white blood cells (WBCs). It is caused by increases in the number of precursor cells that will eventually grow into mature WBCs. This may occur in infections, bleeding from the digestive tract, cancer, or destruction of red blood cells in the blood. This is diagnosed based on patient history, physical examination, and laboratory examination for extensive bleeding and blood cell destruction.

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