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Sumana Devata

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date: 23 May 2022

  1. A. Introduction

    1. a. The circulating pool of white blood cells (WBCs, leukocytes) consists of:

      1. i. Neutrophils

      2. ii. Lymphocytes

      3. iii. Monocytes

      4. iv. Eosinophils

      5. v. Basophils

    2. b. Definitions

      1. i. Leukocytosis. Defined as the total WBC count exceeding 11,000 cells/μ‎L

      2. ii. Leukemoid reaction. Occurs when the leukocyte count exceeds 50,000 cells/μ‎L. There is often evidence of a “left shift”—presence of early neutrophil precursors (myelocytes, metamyelocytes, and bands)—on the peripheral blood smear. This is not a formal diagnosis, and etiologies such as primary bone marrow disorders must be considered. However, the leukemoid reaction may also simply reflect a healthy bone marrow that is reacting appropriately to external stimuli (e.g., trauma, inflammation, infection, malignancy).

      3. iii. Leukoerythroblastosis. This term is used when there is evidence of immature WBCs and nucleated red blood cells (RBCs) on the peripheral smear, regardless of the total WBC count. Leukoerythroblastosis usually implies bone marrow infiltration either by a metastatic cancer, a hematopoietic malignancy, or an infection.

    3. c. Because each cell type can be increased in response to various stimuli, determining the predominant cell type in patients with leukocytosis may offer some insight into the cause.

  2. B. Neutrophilia is defined as a neutrophil count that exceeds 7700 cells/μ‎L.

    1. a. Causes of neutrophilia. Neutrophilia can be caused by many of the major disease categories discussed in Chapter 1 and outlined in Table 64.1.

      Table 64.1 Common Causes of Neutrophilia

      Category of Disease

      Specific Causes


      Hemolytic anemia, splenectomy, chronic myelogenous leukemia

      Pregnancy related

      Pregnancy-induced neutrophilia


      Corticosteroids, lithium, mercury, ethylene glycol


      Hyperthyroidism, ketoacidosis


      Rheumatoid arthritis, vasculitis, gout, acute myocardial infarction, allergic reaction


      Bacteria, viruses, fungi, parasites


      Myeloproliferative neoplasms, myelodysplastic syndromes, acute myeloid leukemia, gastrointestinal or renal malignancy, melanoma, Hodgkin’s disease


      Postsurgery, insects bites, jellyfish stings, crush injuries, electric shock

    2. b. Approach to the patient. Whenever neutrophilia is present, infection is the most important initial consideration. If infection and other nonmalignant disorders are excluded, then a search for neoplasm (which may include a bone marrow biopsy) is warranted. Acutely infected or injured patients have elevated levels of endogenous glucocorticoids, which in turn will lead to low levels of eosinophils and basophils. The presence of eosinophils and basophils in acutely-ill patients is important and usually indicates one of the following:

      1. i. Concomitant adrenal insufficiency

      2. ii. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor

      3. iii. Hematologic malignancy (especially chronic myeloid leukemia [CML])

  3. C. Lymphocytosis is defined as a lymphocyte count that exceeds 4800 cells/μ‎L.

    1. a. Causes of lymphocytosis (Table 64.2). The severity of lymphocytosis may indicate possible causes.

      Table 64.2 Common Causes of Lymphocytosis

      Type of Lymphocytosis

      Specific Causes

      Mild to moderate (4800–15,000/μ‎L)

      Viral illness (e.g., mononucleosis, acute hepatitis A or B, HIV, varicella, influenza, or HTLV-1)

      Secondary to other infections (e.g., pertussis, tuberculosis, toxoplasmosis, syphilis)


      Malignancy (e.g., lymphoma, leukemia)

      Severe (>15,000/μ‎L)

      Viral illness (e.g., mononucleosis, Coxsackie virus, and enteroviruses)


      Malignancy (e.g., lymphoma, leukemia)

      HIV = human immunodeficiency virus; HTLV = human T-lymphotropic virus.

    2. b. Approach to the patient

      1. i. Evaluate for leukoerythroblastosis on the peripheral smear. If present, a bone marrow biopsy is necessary.

      2. ii. If leukoerythroblastosis is not present, a benign cause should be evaluated by history, examination, and laboratory testing.

      3. iii. Perform flow cytometry to assess for clonality of lymphocytes. This can facilitate the diagnosis of malignancy and assess for typical or atypical expression of lymphoid or myeloid markers.

      4. iv. Bone marrow biopsy and aspiration may be required to assess for an underlying hematopoietic process.

  4. D. Monocytosis. Monocytosis is defined as a monocyte count that exceeds 800 cells/μ‎L.

    1. a. Causes of monocytosis (Table 64.3). Monocytes are very important not only in the killing of obligate intracellular parasites (e.g., fungi, parasites, yeast) but also in granulomatous inflammation.

      Table 64.3 Common Causes of Monocytosis

      Category of Disease

      Specific Causes


      Tuberculosis, endocarditis, brucellosis, syphilis, fungal or protozoal infections, CMV, varicella


      Hodgkin’s disease, multiple myeloma, acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes including chronic myelomonocytic leukemia, carcinoma


      Autoimmune hemolytic anemia, ITP, postsplenectomy, chronic neutropenia


      Inflammatory bowel disease, sarcoidosis, connective tissue diseases, myositis, celiac sprue

      CMV = cytomegalovirus; ITP = idiopathic thrombocytopenic purpura.

    2. b. Approach to the patient

      1. i. A comprehensive clinical history of infectious symptoms, sick contacts, or recent travel is important to assess. Additionally, signs of inflammatory or connective tissue diseases should be reviewed.

      2. ii. A peripheral blood smear should be examined to look for signs of concurrent hematologic abnormalities. If the level of monocytosis is extremely high, a hematologic malignancy, including acute myelomonocytic and acute monocytic leukemia, or chronic myelomonocytic leukemia (CMML) should be strongly suspected. Moreover, acute myelomonocytic or monocytic leukemia has a predilection to infiltrate tissues, which may manifest as gingival hypertrophy, leukemia cutis, or leukostasis with WBC counts as low as 50,000 cells/μ‎L.

  5. E. Basophilia is defined as a basophil count that exceeds 200 cells/μ‎L.

    1. a. Causes of basophilia (Table 64.4). Basophils have an important role in the control of parasitic infections but also may have roles in mediating hypersensitivity reactions.

      Table 64.4 Common Causes of Basophilia

      Category of Disease

      Specific Causes


      Food or drug allergy, inflammatory bowel disease, juvenile rheumatoid arthritis


      Diabetes mellitus, ectopic estrogen use, hypothyroidism


      Viral (varicella, influenza, smallpox), tuberculosis, parasitic infections


      Myeloproliferative neoplasms, chronic myeloid leukemia, carcinoma

    2. b. Approach to the patient

      1. i. Evaluate for new exposures to medications or foods.

      2. ii. Assess for infectious symptoms, sick contacts, or recent travel.

      3. iii. If no clear underlying etiology is found, consider a bone marrow biopsy and molecular testing for a myeloid leukemia or myeloproliferative neoplasms.

Suggested Further Readings

Chabot-Richards DS, George TI. Leukocytosis. Int J Lab Hematol 2014;36:279–88.Find this resource:

Fathi AT, Graubert TA, Kulkarni NM, Kuo FC, Hasserjian RP. Case 37-2016. N Engl J Med 2016;375:2273–82.Find this resource:

Macintyre EA, Linch DC. Lymphocytosis: is it leukaemia and when to treat. Postgrad Med J 1988;64:42. (Classic Article.)Find this resource:

Vignola AM, Gjomarkaj M, Arnoux B, Bousquet J. Monocytes. J Allergy Clin Immunol 1998;101:149–52. (Classic Article.)Find this resource: