Granulocytopenia And Lymphocytopenia

Granulocytopenia is characterized by a marked reduction in the number of circulating granulocytes. Although this implies that all granulocytes (neutrophils, basophils, and eosinophils) are reduced, granulocytopenia usually refers to decreased neutrophils, a condition known as neutropenia. This disorder, which can occur at any age, is associated with infections and ulcerative lesions of the throat, GI tract, other mucous membranes, and skin. Its severest form is known as agranulocytosis.

A rare disorder, lymphocytopenia (lymphopenia) is a deficiency of circulating lymphocytes (leukocytes produced mainly in lymph nodes).

In granulocytopenia and lymphocytopenia, the white blood cell (WBC) count may reach dangerously low levels, leaving the body unprotected against infection. The prognosis in both disorders depends on the underlying cause and whether it can be treated. Untreated, severe granulocytopenia can be fatal in 3 to 6 days.

Causes

Granulocytopenia may result from diminished production of granulocytes in bone marrow, increased peripheral destruction of granulocytes, or greater use of granulocytes. Diminished production of granulocytes in bone marrow generally stems from radiation therapy or drug therapy, is a common adverse effect of antimetabolites and alkylating agents, and can occur in the patient who is hypersensitive to phenothiazines, sulfonamides (and some sulfonamide derivatives, such as chlorothiazide), antibiotics, or antiarrhythmics. Drug-induced granulocytopenia usually develops slowly and typically correlates with the dosage and duration of therapy. Granulocyte production also decreases in such conditions as aplastic anemia and malignant bone marrow diseases and in some hereditary disorders (infantile genetic agranulocytosis).

The growing loss of peripheral granulocytes results from increased splenic sequestration, diseases that destroy peripheral blood cells (viral and bacterial infections), and drugs that act as haptens (carriers of antigens that attack blood cells, causing acute idiosyncratic or non-dose-related drug reactions). Infections such as mononucleosis may cause granulocytopenia because of the increased use of granulocytes.

Similarly, lymphocytopenia may result from decreased production, increased destruction, or loss of lymphocytes. Decreased lymphocyte production may result from a genetic or thymic abnormality or from an immunodeficiency disorder, such as thymic dysplasia or ataxia-telangiectasia. Increased lymphocyte destruction may be caused by radiation therapy, chemotherapy, or human immunodeficiency virus infection. Loss of lymphocytes may follow postoperative thoracic duct drainage, intestinal lymphangiectasia, and impaired intestinal lymphatic drainage (as in Whipple's disease). Lymphocyte depletion can also result from elevated plasma corticoid levels (due to stress, corticotropin or steroid therapy, or heart failure). Other disorders associated with lymphocyte depletion include Hodgkin's disease, leukemia, aplastic anemia, sarcoidosis, myasthenia gravis, lupus erythematosus, protein-calorie malnutrition, renal failure, terminal cancer, tuberculosis and, in infants, severe combined immunodeiciency disease (SCID).

Diagnostic tests

Diagnosis of granulocytopenia necessitates a thorough patient history to check for precipitating factors. Physical examination for clinical effects of underlying disorders is also essential.

Treatment

Effective management of granulocytopenia must include identifying and eliminating the cause and controlling infection until the bone marrow can generate more leukocytes. This often means that drug or radiation therapy must be stopped and antibiotic treatment begun immediately, even before test results are known. Treatment may also include antifungal preparations. Administration of granulocyte- or granulocyte­macrophage colony-stimulating factor (G-CSF or GM-CSF) is another treatment used to stimulate bone marrow production of neutrophils. Spontaneous restoration of leukocyte production in bone marrow generally occurs within 1 to 3 weeks.

Treatment of lymphocytopenia includes eliminating the cause and managing the underlying disorder. For an infant with SCID, therapy may include bone marrow transplantation.

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