Leukocytosis

Leukocytosis
n., plural: leukocytosiss
[ˌluːkəʊsaɪˈtəʊsɪs]
Definition: An abnormal increase in white blood cell count in the blood

What Is Leukocytosis?

Leukocytosis is a condition wherein the number of White Blood Cells (WBCs) is increased above the normal levels (as per the age of the patient), i.e., more precisely, a WBC count >11000µl in a non-pregnant adult human. The number of WBCs changes with age, and hence, due consideration is necessary to establish the condition of leukocytosis.

For an adult, 30 × 109/L are the normal levels of WBC count/ total leukocyte count in the body (Figure 1). Interestingly, the total amount of WBC is highest in newborns followed by infants.

WBCs or leukocytes are the defense cells of the body that help to protect the body against pathogen attacks. Generally, the number of leukocytes increases when the body is fighting against viral infections or bacterial infections and WBCs are doing the job of eliminating the pathogen from the body. Thus, in such cases, it is a normal immune response of the immune system. However, certain abnormal conditions like malignancy and autoimmune disease may also induce an increase in the number of WBCs.

Leukocytosis or elevated white blood cells, is more often, transient or chronic, and is due to an inflammatory condition in the body. The inflammation induces a cytokine cascade that results in elevated levels of WBCs. However, leukocytosis may be induced due to an autonomous myeloproliferative neoplasm like bone tumors and leukemia. Pregnancy and labor, epilepsy, strenuous exercise, stress, anesthesia, and drugs like lithium and epinephrine may result in leukocytosis.

Five types of cells constitute WBCs, which are:

• Neutrophils – Neutrophils are a type of white blood cells that are the first defense cells that respond against a pathogen attack on the body.
• Lymphocytes – T and B Lymphocyte cells help to defend the body against specific pathogens.
• Basophils – Histamine-releasing cells that provide non-specific defense against the pathogens.
• Eosinophils – Responsible for allergic reactions usually but these cells also function against microbial infection.
• Monocytes – These cells help to remove the inactivated pathogens.

Types Of Leukocytosis

Leukocytosis is a broad term that refers to the elevated numbers of WBCs. However, depending on the number of specific cells, leukocytosis can result in various white blood cell disorders, which include:

• Neutrophilia

An increase in the number of neutrophils, above the normal range is referred to as neutrophilia. An Absolute Neutrophil Count (ANC) ranges from 2500 to 7000 neutrophils/µl in an adult. ANC is the percentage of neutrophils found in the blood and is the neutrophil count reference interval. Neutrophilia is the most common form of leukocytosis and neutrophil count>7700 neutrophils/µl in an adult is considered as neutrophilia. Inflammation, infection, or any neoplasm may result in neutrophilia. Neutrophilia is also seen in sickle cell disease.

• Lymphocytosis

An increased count of lymphocytes is referred to as lymphocytosis. In terms of the Absolute Lymphocyte Count (ALC), lymphocytes >4000 lymphocytes/ µl, in an adult is referred to as lymphocytosis. However, the type of lymphocyte that has increased, i.e., T-, B- Lymphocyte, will depend on the cause of the lymphocytosis. In diseases like tuberculosis, Grave’s disease, and Crohn’s disease, lymphocytosis is observed.

• Monocytosis

An increased count of monocytes is referred to as monocytosis. Monocyte count can increase in case of an infection, autoimmune disorder, use of certain drugs, and blood disorder.

• Eosinophilia

An increase in the count of eosinophils, as seen in the case of an allergy, is referred to as Eosinophilia. In the case of Eosinophilia, eosinophil count> 500/µL.

• Leukostasis

It is an extreme emergency condition wherein the WBC count is>100,000 µL and is usually seen in the case of acute myeloid leukemia.

Symptoms Of Leukocytosis

A person having leukocytosis may exhibit all or some of the following symptoms:

• Pain
• Easy bruising
• Fever
• Wheezing
• Breathing difficulty
• Itching/hives
• Night sweats
• Weight loss

Causes Of Leukocytosis

Leukocytosis can be malignant or non-malignant. The causes of leukocytosis can be:

• Infection, which can be viral infection (Cytomegalovirus, HIV Epstein-Barr Virus (EBV), influenza, measles, etc.), bacterial infection (tuberculosis, Bartonella henselae, Bordetella pertussis, etc.) or parasitic infections (Babesiosis, Toxoplasma gondii)
• Smoking
• Obesity
• Genetic disorders like Down’s syndrome
• Chronic inflammation in diseases like Inflammatory bowel disease, Rheumatoid arthritis, Chronic hepatitis
• Certain drugs like vancomycin, allopurinol, sulfa drugs, and carbamazepine, can cause eosinophilia. Leukocytosis may also be due to the glucocorticoid treatment
• Emotional stress and physical stress
• Asplenia – Post splenectomy may exhibit lymphocytosis
• Leukocytosis is also seen in the case of pregnancy, wherein the WBC count varies between 5,800 and 13,200 /µL.

Diagnosis

Diagnosing leukocytosis involves taking a medical history, physical examination (for checking enlargement of lymph nodes, spleen, liver, etc.), and detailed analysis of diagnostic tests prescribed by the healthcare provider.

• Leukocyte counts

• » White Blood Cell count between 4,500 and 11,000/µL of blood in a non-pregnant adult – Normal Adult
• » WBC counts between 50,000 and 100,000 /µL of blood- Severe infection/ solid tumor or organ rejection and blood cultures are required to establish the serious bacterial infections.
• » White blood cell (WBC) count >100,000 /µL of blood- Leukemia/ blood cancers or bone marrow cancer or organ rejection

Some of the common diagnostic tests carried out include:

• » Complete Blood Count (CBC) – Complete Blood Count (CBC) is the most common and primary test carried out to profile blood cells and their count. White blood cell differential is carried out for a detailed analysis and diagnosis.
• » Peripheral blood smear – Herein the blood smear on the glass slide is observed under the microscope. It is usually carried out in case of neutrophilia or lymphocytosis. However, this test can not differentiate different types of leucocytes.
• » Bone marrow biopsy – A bone marrow test is used to establish bone marrow involvement and differentiate benign and malignant, i.e., malignant or benign leukocytosis cause for diseases like leukemia/blood cancer. Herein, the blood samples from bone marrow are taken from the center of the bone marrow and the sample is then observed under a microscope and checked for abnormal cells.

Special Laboratory Tests:

• » Flow Cytometry: Flow cytometry of the peripheral blood sample is evaluated for differentiating the proliferating monoclonal cells to determine the abnormal cells present in the blood sample. Certain cases may need bone marrow stimulation to understand the cause.
• » Fluorescence in situ hybridization (FISH), karyotype, along with mutation analysis: These analyses are utilized to diagnose and risk screening for blood malignancy cases like Chronic Lymphocytic Leukemia (CLL) and lymphoma.

Treatment For Leukocytosis

Management of leukocytosis involves finding the reason for leukocytosis and then treating it accordingly. Some of these approaches are:

• In case of eosinophilia or allergic reaction, treatment with anti-histamine
• Antibiotics for the treatment of infectious diseases like Bartonella henselae, MTB, HIV, or toxoplasmosis. Colony-stimulating factors may also be administered to fight the infection.
• For asthmatic attack, use of inhalers and nebulizers
• Radiation, stem cell transplant therapy, and chemotherapy for cancer. For the management of CLL, targeted treatments using BCL-2 inhibitor (Venetoclax), PI3K inhibitors (Idelalisib), and BTK inhibitors (Ibrutinib) are given. For Myeloproliferative Neoplasms, that exhibit neutrophilia, a cytoreductive drug, like hydroxyurea is given.
• Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids for inflammatory disorders. Acute infectious mononucleosis is an inflammatory condition that requires the use of NSAIDs and Corticosteroids.
• Use of intravenous fluids for hyperviscosity syndrome

Note that the information contained here is only for educational purposes only. Seek medical/healthcare professionals for accurate and detailed information on any of these conditions.

Prevention Of Leukocytosis

Quick identification of leukocytosis can help in suitable treatment and management of leukocytosis. A detailed analysis of CBC is crucial for the management of leukocytosis. In cases of hyperleukocytosis (leukocytes>100,000/µL) can be indicative of serious emergency medical conditions like, malignancy or myeloproliferative disease. Lymph node analysis, genetic profile, and analysis of organs involved is required in such emergency condition.

Apart from medical approaches, the following approaches are needed to be acquired to prevent leukocytosis

• Active and healthy lifestyle
• Avoiding exposure to allergens
• Practicing and maintaining clean and hygienic habits
• Reducing stress
• Avoiding smoking
• Taking suitable treatment for anxiety and psychological disorders
• Routine blood analysis

Complications Of Leukocytosis

An early identification of acute leukocytosis and its suitable management does not result in any complications. Chronic leukocytosis in itself is not fatal, however, identification of its cause and treatment of the underlying cause is pertinent to avoid any complications.

Patients with acute myeloid leukemia exhibit Hyperleukocytosis (>100,000 cells/µL), which can lead to leukostasis. WBC lowering drugs like, hydroxyurea are given in such a case to improve blood flow. However, leukocytosis wherein, the WBC count is > 25 X 109/mL can result in complications and fatal conditions. At such a high WBC count, hyperviscosity syndrome sets in, which is usually seen in cases of lymphoma, leukemia, and myeloproliferative disorders. The complications in such a condition range from visual disturbances to multiple organ failure. Hence, suitable treatment of such a condition is necessary.

Patients with CLL are at a potentially high risk of developing secondary malignancy. Drug reaction with eosinophilia and systemic symptoms (DRESS) can result in involvement and complications of multiple organs like the liver, kidney, and lungs.

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References

1. Abramson, N., & Melton, B. (2000). Leukocytosis: basics of clinical assessment. American family physician, 62(9), 2053–2060.
2. Chabot-Richards, D. S., & George, T. I. (2014). Leukocytosis. International journal of laboratory hematology, 36(3), 279–288. https://doi.org/10.1111/ijlh.12212
3. George T. I. (2012). Malignant or benign leukocytosis. Hematology. American Society of Hematology. Education Program, 2012, 475–484. https://doi.org/10.1182/asheducation-2012.1.475
4. Mank, V., Azhar, W., & Brown, K. (2023). Leukocytosis. In StatPearls. StatPearls Publishing.

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