What Is Leukopenia?

Overview

Leukopenia is a condition where the total circulating white blood cell (WBC) count is abnormally low. This can be a reduction in any of the major WBC subtypes (neutrophils, lymphocytes, monocytes, eosinophils, or basophils) but is most commonly associated with reductions in neutrophils (causing neutropenia) and lymphocytes.¹ As a result, the terms leukopenia and neutropenia are often used interchangeably. However, in actuality, neutropenia is a subset of leukopenia. The causal factors of leukopenia show great variety, with acquired forms being the most common and congenital forms of leukopenia being the rarest. The dramatic loss of WBC could be the result of reduced production or increased utilisation/destruction; though leukopenia itself does not have any symptoms, the major danger posed is the risk of secondary infections.² In many cases, WBC levels can return to normal levels on their own; however, in severe leukopenia cases, treatments in the form of antibiotics or growth factors are often administered. 

Causes of leukopenia

The pathogenesis of leukopenia is the result of either:

1. Reduced production of WBC
2. Increased utilisation/destruction of WBC
3. Sequestration of WBC outside of circulating blood pool

The pathogenesis of leukopenia increases the susceptibility of an individual to develop secondary infections. However, the causal factors inducing leukopenia and neutropenia can vary. Some factors are outlined in the table below:

The major causes of leukopenia include:

• Chemotherapy/Radiation- Chemotherapy may damage normal cells like neutrophils in the process. When WBCs are destroyed at a rate faster than the bone marrow can produce new ones, neutropenia is induced.
• Drug-induced causes- The pathogenesis of different drug-induced neutropenia is heterogeneous; however, two categories of drug-induced neutropenia have been recognised:
  • Predictable reactions: Characterised by immune destruction. Drugs such as cancer chemotherapeutic agents will interfere with cell production by either injuring stem cells or slowing down cell division, thus inducing consistent neutropenia.
  • Idiosyncratic reactions: Characterised by direct marrow suppression. These are more prevalent in the elderly, women, and patients with a strong history of allergies. Here, bone marrow aplasia occurs when the bone marrow is either empty or contains very few blood cells. 

• Infections- Viral infections are a common cause of neutropenia due to bone marrow suppression or peripheral destruction. For example, approximately 70% of HIV patients are neutropenic during their illness; the disease not only suppresses WBC production but increases the risk of acquiring other infections.³ Any bacterial infection can also cause neutropenia, though neutropenia in fungal infections is more unusual. 
• Blood cancers- Benign and malignant hematopoietic (formation of new blood cells) diseases may cause neutropenia.³ This is because of the suppression of normal myelopoiesis. This is the process by which myeloid cells are produced in the bone marrow, which differentiate and mature into immune cells like neutrophils. 

Signs and symptoms of leukopenia

The degree of severity of neutropenia (a major factor causing leukopenia) is often graded and, as a result, has differential functional consequences:⁴

• Mild- Absolute neutrophil count below 1.0-1.5 x 10^9/L 

Does not impair host defence, but it is worth investigating the underlying cause.

• Moderate- Absolute neutrophil count 0.5-1.0 x 10^9/L 

Slightly increases the risk of infections, more so in individuals who have a slightly weakened immune system.

• Severe- Absolute neutrophil count 0.2-0.5 x 10^9.L or less 

Risk of severe life-threatening infections.

The symptoms of neutropenia also vary according to the casual type of neutropenia:

Though the manifestation of symptoms varies, common leukopenia symptoms include:

• Nausea
• Fatigue- Extreme tiredness
• Infections that go on for a long time/keep coming back
• Painful mouth ulcers
• Loss of appetite

Management and treatment for leukopenia

• Antibiotics- Broad-spectrum antibiotics are used for acutely ill patients with neutropenia.
• G-CSF administration- Granulocyte-colony stimulating factor is a manufactured version of the natural hormone that stimulates the bone marrow to produce neutrophils.⁵ G-CSF is able to mimic this and is recommended in patients with severe congenital neutropenia or with any form of severe chronic neutropenia.
• Bone marrow transplantation- Used to treat patients with severe chronic neutropenia where chemotherapy is administered to destroy existing bone marrow that is then replaced with bone marrow from a donor through intravenous infusion. 
• Genetic counselling- This can be sought out by individuals with a familial form of chronic neutropenia to understand their own risks of neutropenia.

Diagnosis

The diagnosis and investigations of leukopenia involve the following:

• Family history- Leukopenia/Neutropenia can be heritable so the understanding of family medical history is an important initial step in a patient’s assessment for neutropenia.
• Blood cell counts- Blood counts should be taken 3 times per week over 21-day cycles to establish the absolute neutrophil counts and whether or not the neutropenia is acute (days to weeks) or chronic (months to years).⁴ For autoimmune neutropenia, antibody levels to neutropenia may be measured. 
• Clinical context- Understand the context of the patient, whether it is a newborn, anyone undergoing chemotherapy, is a reaction to new medications, or a secondary response to other inherited diseases.
• Physical examination- Examination of any physical manifestations of the disease, such as mouth ulcers, abscesses, cellulitis, or gingivitis. 

Complications

Chemotherapy/radiation treatment is a common causal factor for neutropenia. This means that patients may have to delay treatment or reduce treatment dosage to prevent further neutropenia or to prevent the condition from worsening. 

FAQs

How can I prevent leukopenia?

Leukopenia is not a condition that can be prevented. However, action can be taken to prevent infections when your WBC count is low, for example, maintaining a good hygiene routine, proper storage and preparation of food, and avoiding close contact with people who are sick. 

How common is leukopenia?

Primary neutropenia, particularly in children, is very rare and is usually associated with heredity. However, leukopenia is more common in patients undergoing chemotherapy/radiation.

Who is at risk of leukopenia?

Individuals who have autoimmune diseases, certain infections such as HIV, are taking certain medications, or undergoing chemotherapy/radiation are at an increased risk of leukopenia. 

What can I expect if I have leukopenia?

Leukopenia itself does not have any symptoms, but as it increases your risk of developing infections, symptoms such as fevers, nausea, and mouth ulcers are not uncommon. Depending on the reason why you have contracted leukopenia, you can expect your WBC to return to normal levels or you may be given treatment and carefully managed by your doctors. 

When should I see a doctor?

If you have a family history of leukopenia, are experiencing any of the symptoms outlined above, are undergoing chemotherapy, or are taking medications which may increase your risk of leukopenia, then it is best to seek out your healthcare provider. 

Summary

Leukopenia is a disorder that is most commonly acquired from triggers such as chemotherapy, certain medications, viral infections, or autoimmune diseases. Though congenital forms of leukopenia exist, they are rare. Leukopenia itself does not exhibit any symptoms; however, the dramatic loss of WBC via bone marrow suppression or immune destruction increases the risk of developing and sustaining infections. Management of Leukopenia is dependent on what caused the leukopenia, with treatments ranging from self-remitting, antibiotics, and growth factor stimulants to bone marrow transplantation.