Overview

Blood is composed of many elements. When running exams, these elements can be counted and referred to as being within a normal amount, more than usual or less than usual. Those counts, in combination with other observations, can guide the physician to assess a patient's health status. The term “monocytosis” refers to a high count of monocytes in blood; the opposite, low count of monocytes, is called “monocytopenia”. In general, it means that defense cells are more active than expected. That alone doesn’t mean a worrisome diagnosis, but it can advise further investigation.¹

Monocytosis can be expected in pregnancy and intense workouts, but also in medical conditions such as infections, trauma, autoimmune diseases, malignancies and bone marrow disorders. When properly functioning, bone marrow produces part of the monocytes that, when matured, will flow into blood vessels as a body support in inflammation sites. Disorders affecting bone marrow can easily cause alterations in monocytes levels.²

Monocytes

Monocytes are white blood cells, a type known as the defensive cells, derived from bone marrow. Whenever there’s an infection or inflammation, the body triggers an innate immune response. Part of that response is the recruitment of monocytes. Once they arrive at the site, they receive signals to differentiate into the cells needed for the immune attack. These new cells can, for example, fight a strange organism, capture and destroy potentially dangerous substances and get rid of dead or dysfunctional cells. When there is no need for the coordination of an immune response, a number of monocytes circulate, patrolling.³

Monocytes have subtypes that differ in structure and functionality, so disturbances in count may require an identification of the type of monocyte in dysfunction.⁴

A laboratory blood investigation can report counts for its component cells. It presents the count of red or white blood cells. Then, each category within the reds or whites. A normal and expected count of the circulating monocytes is from 2% to 8% of white blood cells.⁵  

Common Causes of Monocytosis

Monocytosis alone does not present significant clinical signs. The patient will manifest symptoms of the disease that is causing an increase in monocytes. Cases of monocytosis can be divided into reactive or clonal.

Reactive Monocytosis 

Transient conditions can cause an increase in monocytes in a reversible way. Some examples are bone marrow recovery after chemotherapy, a few medications, acute infectious conditions, body stress due to surgeries, stroke and exercise.

The body may go under a persistent state of monocytosis for chronic infectious diseases like syphilis, malaria and tuberculosis. The same can happen due to chronic inflammatory diseases and radiation therapy.⁴

Clonal Monocytosis

Clonal monocytosis is related to neoplasms, when a tissue presents abnormal growth. Common examples are specific types of both acute and chronic neoplasms, the state in which a tissue is abnormally growing. Acute disorders in this category include Acute myeloid leukemia (AML) and Dendritic cell leukemia. Chronic disorders in this category include Chronic myelomonocytic leukemia (CMML), Myeloproliferative neoplasms and some Myeloid neoplasms.⁴

Bone Marrow

Bone marrow is a soft tissue inside human bones cavities, it is mainly responsible for blood cell production. This process is called hematopoiesis and occurs because the bone marrow tissue is a shelter for stem cells, cells that aren’t specialized yet, immature. Stem cells are able to differentiate, transform into a variety of functioning cells. That is the birthplace of blood cells.⁵

Common Bone Marrow Disorders 

• Leukemia: A varied group of hematologic cancers related to abnormal proliferation of leukocytes, a type of white blood cells, in the bone marrow⁶
• Myelodysplastic Syndromes (MDS): A broad term for dysfunctional overgrowth of immature blood cells leading to defective hematopoiesis, the production of proper cells, in the bone marrow⁷
• Myeloproliferative disorders: A broad term for a variety of disorders, in the bone marrow, that cause abnormal proliferation of groups of blood cells that are not fully immature but are able to specialize in a few specific matured cells⁸

Monocytosis in Bone Marrow Disorders

Chronic Myelomonocytic Leukemia (CMML)

One of the main characteristics of chronic myelomonocytic leukemia is the establishment of persistent monocytosis. It is considered persistent if it lasts more than 3 months⁹.

Myelodysplastic Syndromes (MDS)

This group of disorders present impaired and dysfunctional hematopoiesis, so production of blood cells is defective by the bone marrow. Although it does not happen for all myelodysplastic syndromes, abnormal production of monocytes and its precursors can occur. Recent studies point to the possibility of a negative prognostic for MDS patients who present increased production of monocytes.^10,4

Myeloproliferative Neoplasms

Neoplasms refer to abnormal growth of cells. In myeloproliferative neoplasms, in general, blood related cells, including monocytes, and their precursors are the ones being over proliferated.⁴

Acute Myeloid Leukemia (AML)

The acute myeloid leukemia diagnosis is usually established when the patient's exams indicate a high percentage of immature blood cells, including monocyte precursor cells either in blood or bone marrow.¹¹

Diagnostic Approaches

Blood Tests 

The complete blood count (CBC) provides valuable health information for doctors, as blood carries evidence of a variety of possible medical conditions. It is one of the most commonly requested laboratory investigations and mainly assesses red blood cell count (RBC), white blood cell count (WBC) and counts for differentiated cells constituting both. 

If the total counts are abnormal, the differentiated cells can specify which component is imbalanced. For WBC, if the count is not within the range of 4500 to 11000 cells/μL, counts for monocytes, neutrophils, lymphocytes, eosinophils and basophils accuse where the misproportion lies. Monocyte counts, in normal conditions, present within 200 to 1000 cells/µL.¹²

Bone Marrow Biopsy and Aspiration 

Both the bone marrow aspiration and biopsy are investigative techniques able to provide a detailed observation of the bone marrow environment and cell population. Access to such information can support a variety of diagnosis, especially for hematologic disorders, which might have been unclear from previous exams. For being quick, not needing sedation and avoiding more invasive procedures, these methods are still highly recommended for disorders regarding bone marrow and the blood components.^11,13

Flow Cytometry 

Flow cytometer is a laboratory machinery able to analyze sampled cell population. The sample is a tissue of interest processed to be dispersed in a solution. This solution goes through a laser in the flow cytometer. Particles on the solution can absorb and/or reflect the light from the laser and this will become information read by components of the machine. Cells in the solution may be fluorescently tinted to highlight its subcomponents. Gathering these data can provide information on whole cell populations, enabling identification on the type of cell growing in the analyzed tissue. It is commonly used to investigate disorders in blood and bone marrow.¹⁴

Genetic Testing

There is a group of hereditary bone marrow disorders. They must be differentiated from other bone marrow medical conditions, as the carrier of such genetic material has a predisposition to manifest the disorder, they’re disorder trigger is specific. Confirming it with genetic testing can provide enough information to proceed with the patient’s treatment. When bone marrow transplant is recommended for these cases, usually the donor is not from the same family. There is a technique in which the patient's bone marrow immature cells are collected, treated and reimplanted; genetic evidence of hereditary bone marrow disorder, in this case, enables the health professional to perform specific treatments for the cells before reimplantation.¹⁵

Summary

Monocytes are a type of white blood cell mostly produced by the bone marrow. It is usually involved in immune responses in sites of inflammation, infection and abnormal cell growth. It is recruited by the body to immobilize and get rid of potentially dangerous elements in these scenarios. Immature forms of monocytes grow and start to differentiate within the bone marrow. Disturbances in the bone marrow tissue may affect this process and cause an imbalance in production and recruitment of cells. Monocytosis, increased presence of monocytes, can occur as a response to these defects. As a part of the functionality and environment, monocytes can be easily affected by bone marrow disorders. Diagnostic tools can determine if there is an establishment of monocytosis, what type of monocyte is involved and if there is a genetic factor. Such information can guide the treatment approach that will target the disorder causing monocytosis.