At a Glance

Monocytosis is defined as an absolute monocyte count greater than 2SD above the mean for the patient population. Typically, this represents a monocyte count greater than 800 per microliter in adults. Monocyte counts may be significantly higher in children (e.g., up to 3000 per microliter), and age-specific normals should be used to determine if the monocyte count is truly elevated in a younger patient.

Note that a finding of monocytosis should not be based on a differential count reported in percentages. Depending on the total white cell count (WBC) an elevation in the percentage of monocytes may reflect either true monocytosis (high WBC), lymphopenia (normal or low WBC), or neutropenia (normal or low WBC). Therefore, the diagnosis of monocytosis should be based on an absolute monocyte count either provided directly by the performing laboratory or calculated (AMC = WBC x % monocytes x 100).

Monocytosis is most commonly associated with sub-acute or chronic infections (e.g., endocarditis, tuberculosis, syphilis, protozoan, or rickettsial infections), collagen vascular disorders, bone marrow recovery, granulomatous inflammation (e.g., sarcoidosis), and hematologic disorders.

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What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

In a patient without an apparent clinical cause or a history of monocytosis, it is probably most appropriate to simply repeat a complete blood count (CBC) on a new sample to confirm that monocytosis is truly present. Although uncommon, sample mislabeling and laboratory error may result in an erroneous or transient monocytosis that may simply disappear on repeat testing. Additionally, monocyte numbers may increase 50-100% after exercise, likely secondary to demargination. The increase tends to parallel the intensity and duration of the exercise.

If monocytosis is present on repeat testing, the next step is to thoroughly review the remainder of the CBC for other abnormalities and ask the laboratory to review a well-made peripheral smear for red cell, white cell, and platelet morphology.

CBC should be reviewed; in particular, look for any of the following: leukocytosis, anemia, polycythemia, thrombocytopenia, thrombocytosis, or high or low mean corpuscular volume (MCV).

Review the peripheral smear. For general assessment, look for evidence of red cell or platelet clumping that may cause spurious leukocytosis and/or monocytosis.

Leukocyte morphology includes presence of immature granulocytes, monocytes, or blasts (leukemoid reaction, leukoerythroblastosis, leukemia, myloproliferastive disorder); monocyte vacuolization, hypergranularity, phagocytosed organism, or cells; neutrophil hypersegmantation (early recovery of vitamin deficiency, myelodysplasia); and pseudo-Pelger-Huet cells (myelodysplasia).

Red cell morphology includes nucleated red cells (marrow infiltration, leukoerythroblastosis, marrow recovery); dysplastic forms (myelodysplasia); intracellular organisms (Malaria sp., Babesia sp.); schistocytes (TTP, HUS, DIC, endocarditis, other microangiopathic processes); sickle cells (HbSS as a cause of asplenia); and marked polychromasia (marrow recovery).

Platelet morphology includes large platelets (marrow recovery) and abnormal platelet shape or granulation (myelodysplasia).

A thorough history and physical exam may be useful in identifying the cause of monocytosis.

History should include:

hematologic disorders or treatments that suppress bone marrow

collagen vascular disorders, such as rheumatoid arthritis and polymyositis

gastrointestinal (GI) disorders, such as sprue, ulcerative colitis, and Crohn’s disease

solid tumors


evidence of or exposure to tuberculosis, rickettsia, or protozoan parasites

full medication history, especially marrow suppressants

evidence of chronic infection, weight loss, fevers, or night sweats


Physical examination should include:

fever, adenopathy

splinter hemorrhages, cardiac murmur, or other evidence of endocarditis

splenomegaly or evidence of splenectomy

skin lesions suggesting sarcoidosis (Erythema nodosum, Lupus pernio)

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Monocytosis may be seen in patients receiving cytokines (GM-CSF, M-CSF) TNF-alpha or drugs that increase levels of IL- 3, IL-6, or IL-1. It has also been described in patients taking Olanzapine, allopurinol, corticosteroids, and Griseofulvin.

Additionally, monocytosis may be a harbinger of early marrow recovery after marrow suppression from drugs or other causes.

What Lab Results Are Absolutely Confirmatory?

Absolute confirmation of monocytosis is provided by repeat CBC with absolute differential count.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

For infectious disorders, the following should be ordered:

chest x-ray for evidence of tuberculosis or sarcoidosis

echocardiography for evidence of endocarditis

C-reactive protein for evidence of inflammation

blood culture for endocarditis

VDRL, RPR for syphilis

PPD or Quantiferon testing for latent tuberculosis

serologic testing for rickettsia if suggested by history

thin and thick smears of peripheral blood to rule out Malaria spp., Babesia spp. if suggested by history

For autoinflammatory disorders, the following should be ordered:

rheumatoid factor, ANA with follow testing as indicated

stool culture, O&P, and C. difficile toxin assay to rule out infectious causes in patients with GI symptoms

sigmoidoscopy and colonoscopy with biopsy to evaluate for UC and Crohn’s disease in patients with GI symptoms