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59 LEUKOCYTOSIS AND LEUKOPENIA

59 LEUKOCYTOSIS AND LEUKOPENIA
Harrison’s Manual of Medicine

59

LEUKOCYTOSIS AND LEUKOPENIA

Leukocytosis

Approach

Neutrophilia

Leukemoid Reaction

Leukoerythroblastic Reaction

Lymphocytosis

Monocytosis

Eosinophilia

Basophilia
Leukopenia

Neutropenia

Lymphopenia

Monocytopenia

Eosinopenia
Bibliography

LEUKOCYTOSIS
Approach
Review smear (? abnormal cells present) and obtain differential count. The normal values for concentration of blood leukocytes are shown in Table 59-1.

Table 59-1 Normal Values for Leukocyte Concentration in Blood

Neutrophilia
Absolute neutrophil count (polys and bands) >10,000/µL. The pathophysiology of neutrophilia involves increased production, increased marrow mobilization, or decreased margination (adherence to vessel walls).
CAUSES   (1) Exercise, stress; (2) infections—esp. bacterial; smear shows increased numbers of immature neutrophils (“left shift”), toxic granulations, Döhle bodies; (3) burns; (4) tissue necrosis (e.g., myocardial, pulmonary, renal infarction); (5) chronic inflammatory disorders (e.g., gout, vasculitis); (6) drugs (e.g., glucocorticoids, epinephrine, lithium); (7) cytokines (e.g., G-CSF, GM- CSF); (8) myeloproliferative disorders (Chap. 63); (9) metabolic (e.g., ketoacidosis, uremia); (10) other—malignant neoplasms, acute hemorrhage or hemolysis, after splenectomy.
Leukemoid Reaction
Extreme elevation of leukocyte count (>50,000/µL) composed of mature and/ or immature neutrophils.
CAUSES   (1) Infection (severe, chronic, e.g., tuberculosis), esp. in children; (2) hemolysis (severe); (3) malignant neoplasms (esp. carcinoma of the breast, lung, kidney); (4) cytokines (e.g., G-CSF, GM-CSF). May be distinguished from chronic myeloid leukemia (CML) by measurement of the leukocyte alkaline phosphatase (LAP) level: elevated in leukemoid reactions, depressed in CML.
Leukoerythroblastic Reaction
Similar to leukemoid reaction with addition of nucleated RBCs and schistocytes on blood smear.
CAUSES   (1) Myelophthisis—invasion of the bone marrow by tumor, fibrosis, granulomatous processes; smear shows “teardrop” RBCs; (2) myelofibrosis—same pathophysiology as myelophthisis, but the fibrosis is a primary marrow disorder; (3) hemorrhage or hemolysis (rarely, in severe cases).
Lymphocytosis
Absolute lymphocyte count >5000/µL.
CAUSES   (1) Infection—infectious mononucleosis, hepatitis, CMV, rubella, pertussis, tuberculosis, brucellosis, syphilis; (2) endocrine disorders— thyrotoxicosis, adrenal insufficiency; (3) neoplasms—chronic lymphocytic leukemia (CLL), most common cause of lymphocyte count >10,000/µL.
Monocytosis
Absolute monocyte count >800/µL.
CAUSES   (1) Infection—subacute bacterial endocarditis, tuberculosis, brucellosis, rickettsial diseases (e.g., Rocky Mountain spotted fever), malaria, leishmaniasis; (2) granulomatous diseases—sarcoidosis, Crohn’s disease; (3) collagen vascular diseases—rheumatoid arthritis, SLE, polyarteritis nodosa, polymyositis, temporal arteritis; (4) hematologic diseases—leukemias, lymphoma, myeloproliferative and myelodysplastic syndromes, hemolytic anemia, chronic idiopathic neutropenia; (5) malignant neoplasms.
Eosinophilia
Absolute eosinophil count >500/µL.
CAUSES   (1) Drugs, (2) parasitic infections, (3) allergic diseases, (4) collagen vascular diseases, (5) malignant neoplasms, (6) hypereosinophilic syndromes.
Basophilia
Absolute basophil count >100/µL.
CAUSES   (1) Allergic diseases, (2) myeloproliferative disorders (esp. CML), (3) chronic inflammatory disorders (rarely).
LEUKOPENIA
Total leukocyte count <4300/µL.
Neutropenia
Absolute neutrophil count <2000/µL (increased risk of bacterial infection with count <1000/µL). The pathophysiology of neutropenia involves decreased production or increased peripheral destruction.
CAUSES   (1) Drugs—cancer chemotherapeutic agents are most common cause, also phenytoin, carbamazepine, indomethacin, chloramphenicol, penicillins, sulfonamides, cephalosporins, propylthiouracil, phenothiazines, captopril, methyldopa, procainamide, chlorpropamide, thiazides, cimetidine, allopurinol, colchicine, ethanol, penicillamine, and immunosuppressive agents; (2) infections—viral (e.g., influenza, hepatitis, infectious mononucleosis, HIV), bacterial (e.g., typhoid fever, miliary tuberculosis, fulminant sepsis), malaria; (3) nutritional—B12, folate deficiencies; (4) benign—mild cyclic neutropenia common in blacks, no associated risk of infection; (5) hematologic diseases—cyclic neutropenia (q21d, with recurrent infections common), leukemia, myelodysplasis (preleukemia), aplastic anemia, bone marrow infiltration (uncommon cause), Chédiak-Higashi syndrome; (6) hypersplenism—e.g., Felty’s syndrome, congestive splenomegaly, Gaucher’s disease; (7) autoimmune diseases—idiopathic, SLE, lymphoma (may see positive antineutrophil antibodies).

TREATMENT
Of the Febrile, Neutropenic Patient (See Chap. 42) In addition to usual sources of infection, consider paranasal sinuses, oral cavity (including teeth and gums), anorectal region; empirical therapy with broad-spectrum antibiotics (e.g., ceftazidime) is indicated after blood and other appropriate cultures are obtained. Prolonged febrile neutropenia (>7 d) leads to increased risk of disseminated fungal infections; requires addition of antifungal chemotherapy (e.g., amphotericin B). The duration of chemotherapy-induced neutropenia may be shortened by a few days by treatment with the cytokines GM-CSF or G-CSF.

Lymphopenia
Absolute lymphocyte count <1000/µL.
CAUSES   (1) Acute stressful illness—e.g., myocardial infarction, pneumonia, sepsis; (2) glucocorticoid therapy; (3) lymphoma (esp. Hodgkin’s disease); (4) immunodeficiency syndromes—ataxia telangiectasia and Wiskott-Aldrich and DiGeorge’s syndromes; (5) immunosuppressive therapy—e.g., antilymphocyte globulin, cyclophosphamide; (6) large-field radiation therapy (esp. for lymphoma); (7) intestinal lymphangiectasia (increased lymphocyte loss); (8) chronic illness—e.g., CHF, uremia, SLE, disseminated malignancies; (9) bone marrow failure/replacement—e.g., aplastic anemia, miliary tuberculosis.
Monocytopenia
Absolute monocyte count <100/µL.
CAUSES   (1) Acute stressful illness, (2) glucocorticoid therapy, (3) aplastic anemia, (4) leukemia (certain types, e.g., hairy cell leukemia), (5) chemotherapeutic and immunosuppressive agents.
Eosinopenia
Absolute eosinophil count <50/µL.
CAUSES   (1) Acute stressful illness, (2) glucocorticoid therapy.
Bibliography

For a more detailed discussion, see Holland SM, Gallin JI: Disorders of Granulocytes and Monocytes, Chap. 64, p. 366; Young NS: Aplastic Anemia, Myelodysplasia, and Related Bone Marrow Failure Syndromes, Chap. 109, p. 692; Spivak JL: Polycythemia Vera and Other Myeloproliferative Diseases, Chap. 110, p. 701, in HPIM-15.

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