What causes an elevation in monocyte (monos) percentage?

Elevated Monocyte Percentage: Causes and Clinical Approach

Monocytosis has two major categories: reactive (benign) conditions from chronic infections and inflammation, and clonal hematologic malignancies, particularly chronic myelomonocytic leukemia (CMML), which must be systematically excluded in persistent cases. 1

Reactive (Benign) Causes

Infectious Etiologies

• Chronic infections are the most common infectious triggers, specifically tuberculosis and bacterial endocarditis 1
• Viral infections including HIV and hepatitis C can produce monocytosis clinically indistinguishable from primary hematologic disorders 2
• Ehrlichiosis (E. chaffeensis, E. ewingii) presents with monocytosis alongside leukopenia, thrombocytopenia, and elevated hepatic transaminases; look for morulae within monocytes on peripheral smear 2
• Parasitic infections, particularly Strongyloides in patients with travel history 2

Inflammatory and Autoimmune Conditions

• Adult-onset Still's disease produces marked leukocytosis with monocytosis, typically with white blood cell counts >15×10⁹ cells/L 1
• Inflammatory bowel disease (both Crohn's disease and ulcerative colitis) causes chronic monocyte elevation 1, 2
• Systemic lupus erythematosus and other autoimmune disorders frequently elevate monocyte counts 2
• Rheumatoid arthritis is associated with elevated monocyte percentages 2
• Chronic inflammatory conditions of any cause trigger monocyte expansion through persistent cytokine stimulation 1

Cardiovascular Disease

• Atherosclerosis and coronary artery disease correlate with elevated monocyte counts, as monocytes play a pathogenic role in plaque formation 1
• Hypertension is associated with increased CD14++CD16+ monocyte populations that independently predict cardiovascular events 3
• Hypertensive individuals exhibit "primed" monocytes that produce more pro-inflammatory cytokines when stimulated 3

Other Reactive Causes

• Tissue injury and chronic inflammation of any cause 1
• Recovery from bone marrow suppression 2
• Solid tumors: 35 of 44 patients with various solid tumors showed spontaneous elevation of CD16+ monocytes, accounting for 46% ± 22% of total monocytes versus 5% ± 3% in controls 4

Clonal (Malignant) Causes

Primary Hematologic Malignancies

• CMML is the primary hematologic malignancy causing persistent monocytosis and carries the highest relative risk (OR 105.22,95% CI: 38.27-289.30) 1, 5
• WHO 2008 criteria for CMML require: persistent peripheral blood monocytosis (>1×10⁹/L), absence of Philadelphia chromosome or BCR-ABL1 fusion gene, and <20% blasts in blood and bone marrow 1
• Molecular mutations commonly found in CMML include TET2, SRSF2, ASXL1, and RAS 1

Other Malignancies

• Chronic lymphocytic leukemia (CLL): elevated absolute monocyte count correlates with inferior outcomes and accelerated disease progression 2
• Myelodysplastic syndromes (MDS) can present with monocytosis, though absolute monocyte count typically remains <1×10⁹/L 2
• Acute myeloid leukemia and juvenile myelomonocytic leukemia should be considered 2
• Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes may present with monocytosis 2

Clonal Hematopoiesis

• Clonal hematopoiesis (CH) occurs more frequently in older individuals with monocytosis (50.9% vs 35.5% in controls, P < .001) 6
• Monocytosis is associated with enrichment of multiple gene mutations (P = .006) and spliceosome mutations (P = .007) 6
• Persistent monocytosis over 4 years was observed in 30% of individuals and associated with higher CH prevalence (63%) 6

Diagnostic Algorithm

Initial Assessment

• Obtain absolute monocyte count, not just percentage; monocytosis is defined as ≥1×10⁹/L 1, 2
• Detailed history focusing on: travel exposure, new medications, recurrent infections, family history of hematologic malignancies, constitutional symptoms, and chronic inflammatory conditions 2
• Physical examination must assess spleen size, cutaneous lesions, lymphadenopathy, and signs of organ damage 2

Laboratory Evaluation

• Complete blood count with differential to determine absolute monocyte count and assess for concurrent cytopenias 2
• Peripheral blood smear examination to evaluate monocyte morphology, dysgranulopoiesis, promonocytes, blasts, neutrophil precursors, rouleaux formation (suggests plasma cell dyscrasia), and morulae in monocytes (suggests ehrlichiosis) 2
• Comprehensive metabolic panel and liver function tests 2

When to Pursue Hematologic Workup

Bone marrow evaluation is mandated for: 2

• Persistent unexplained monocytosis without clear reactive cause
• Absolute monocyte count ≥1×10⁹/L sustained over time (particularly >3 months) 1
• Concurrent cytopenias or other blood count abnormalities
• Constitutional symptoms or organomegaly
• Dysplastic features on peripheral smear

Advanced Testing

• Bone marrow aspiration and biopsy with Gomori's silver impregnation for fibrosis to assess marrow cellularity, dysplasia, and blast percentage 2
• Conventional cytogenetic analysis to exclude t(9;22) and t(5;12) translocations and identify clonal abnormalities 2
• Molecular testing for BCR-ABL1 fusion gene and mutations in TET2, SRSF2, ASXL1, and RAS genes 1, 2

Critical Clinical Pitfalls

• Distinguish absolute from relative monocytosis: percentage alone is insufficient; calculate absolute count 2
• Do not dismiss sustained monocytosis: in primary care, sustained monocytosis (at least two requisitions in 3 months) increases CMML risk, though diagnosis remains rare (0.1% of these individuals) 5
• Recognize that monocytosis in cancer patients may represent host immune response: this is a widespread but previously unsuspected phenomenon 4
• Do not overlook concurrent conditions: hypertensive patients with monocytosis may have exaggerated inflammatory responses that worsen perioperative outcomes 3
• Perform comprehensive bone marrow evaluation when indicated; failure to do so is a common pitfall 2