Leukopenia – What the diagnosis means

Causes, symptoms and course

Leukopenia or leukocytopenia refers to a lack of white blood cells. It occurs when there is an increased consumption of white blood cells or reduced production in the bone marrow . We explain the most important causes that can trigger leukopenia.

Leukopenia Causes: Different leukocytes, different forms

Leukocytes , the white blood cells, are the front line of our immune system. Therefore, the leukocyte blood level LEUK or WBC ( white blood cells ) is an important parameter for the functionality of the body’s defenses . The reference range for the leukocyte blood value is the same for men and women:

Reference range for leukocytes in blood (LEUK, WBC): 3.8 – 10.5 thousand/µl (microliter).

By definition, one speaks of leukopenia when the leukocyte blood value falls below 3,500 per microliter.

Leukopenia becomes critical when the value is below 800 per microliter. Then more infections occur, which quickly end fatally.

Depending on which type of white blood cell is reduced, one can further differentiate

  • Lymphopenie (Lymphozytopenie)
  • Granulopenia ( granulocytopenia ) – usually in the form of a
    • Neutropenia , since the neutrophils make up the majority of the granulocytes . Reduced numbers of the other, rarer granulocytes, i.e. one, are clinically irrelevant
    • eosinopenia or
    • Basopenia.
  • Monocytopenia with reduced monocytes also plays no clinical role.

Key facts at a glance!

  1. Leukopenia or leukocytopenia refers to a lack of white blood cells (leukocytes).
  2. Since the leukocytes are responsible for the immune system, leukopenia is associated with an increased risk of infection.
  3. Infections with bacteria, viruses and protozoa are among the causes of high consumption of white blood cells in leukopenia.
  4. Other defense tasks such as autoimmune diseases or withdrawal due to an enlarged spleen also lead to a reduction.
  5. Likewise, reduced formation of white blood cells is one of the causes of leukopenia, as is damage to the bone marrow during cancer treatment.

Increased consumption of white blood cells due to infections

Bacteria, viruses and protozoa are attacked and eliminated by white blood cells as they enter the body . Since the blood cells themselves perish in the process, a deficiency in the form of leukopenia quickly occurs in the event of an extensive infection.

  • bacterial infections
    • Blood poisoning (sepsis) – prime example of a trigger for leukopenia
    • Typhus
    • Brucellosis
    • Rickettsial infections
    • Parrot Disease (Psittacosis)
    • Lyme-Borreliose
  • The viral infection
    • Flu
    • measles
    • Mumps
    • rubella
    • Dengue fever
  • parasites
    • Malaria
    • Typhus

Leukopenia when white blood cells are deprived by an enlarged spleen

The spleen is a temporary storage facility for all types of blood cells. In the case of a severely enlarged spleen (hypersplenism, splenomegaly ), many blood cells disappear here and are therefore no longer available for their tasks in the periphery. This applies to all blood cells and thus also to the leukocytes and the resulting leukopenia.

Leukopenia: Increased consumption of white blood cells by autoimmune diseases (autoimmune leukopenia)

In fact, inflammation causes the body to produce more white blood cells. However, especially in the case of autoimmune diseases, he cannot keep up with it quickly enough , so that a lack of white blood cells occurs.

These autoimmune diseases include

    • allergic rhinitis like
      • Hay fever from pollen
      • Allergy to house dust mites
      • Allergy to animal hair
    • Hashimoto – Thyroiditis, in which the thyroid gland is destroyed by immune cells
    • HIV infection/acquired immunodeficiency syndrome (AIDS)
    • systemic lupus erythematosus (butterfly itch)
    • Sjogren’s syndrome (autoimmune disease of the salivary and lacrimal glands)
    • Scleroderma (a pathological hardening of the skin with connective tissue with changes in internal organs)
    • CREST syndrome (a special form of scleroderma)
    • Polymyositis and dermatomyositis (systemic, inflammatory diseases of the skeletal muscles)
    • rheumatic fever
    • rheumatoid arthritis
    • Sharp’s syndrome, a mixed collagen disease with components of lupus erythematosus, scleroderma, polymyositis and rheumatoid arthritis
    • Buschke-Ollendorff syndrome – a rare hereditary connective tissue disease with changes in the skin and skeleton
    • Sarcoidosis ( Boeck’s disease , Löfgren’s syndrome), a systemic connective tissue disease.

Leukopenia due to damage to blood formation caused by cancer therapy

Too few white blood cells are produced when there is damage to the bone marrow (myelosuppression) . Most often, this is the result of cancer treatment that damages all fast-growing cells . This includes not only the cancer cells, but also the blood-forming cells of the bone marrow.

Leukopenia due to damage to the bone marrow by radioactivity

Radioactive radiation also damages the blood-forming cells and leads to leukopenia . This became particularly clear with the radiation victims of atomic bombings and reactor accidents.

Leukopenia due to side effects of drugs

Similarly, some medicines can adversely affect blood formation in the bone marrow. This includes

  • clozapine (a neuroleptic used to treat psychosis)
  • Valproate (valproic acid, against epilepsy)
  • Bupropion (for depression and smoking cessation)
  • Sulfasalazine (an anti-inflammatory drug used in chronic inflammatory bowel disease (IBD) such as Crohn’s disease and ulcerative colitis wodiw in chronic polyarthritis)
  • thiamazole (a drug used to treat an overactive thyroid gland (hyperthyroidism))
  • Interferons (interferon β-1a and interferon β-1b)
  • Rituximab (an antibody against the surface molecule CD20, used as a drug for rheumatoid arthritis and for cancer immunotherapy in non-Hodgkin’s lymphoma)
  • Minocycline (an antibiotic)
  • if allopurinol (for hyperuricemia, gout) and azathioprine (for immunosuppression after organ transplantation) are taken at the same time

Leukopenia cause deficiency symptoms

There is also a reduced production of white blood cells if the body lacks the substances required for this. The vitamin B12 deficiency and a folic acid deficiency should be mentioned here in particular . The same also occurs with a copper deficiency or zinc deficiency .

Suppression of white blood cell formation by malignant disorders

In various types of blood cancer (leukaemia), so many other, mostly non-functional white blood cells are formed that the fully formed ones take a back seat.

In this case, too, one speaks of leukopenia, even if there appear to be a large number of white blood cells in the blood. Functionally, this also leads to a disrupted immune system, since the excess cells produced are unable to carry out their normal tasks.

  • Acute Lymphocytic Leukemia (ALL)
  • Acute myeloid leukemia (AML)
  • Myelodysplastische Syndrome (MDS)
  • Hodgkin’s disease (Hodgkin’s lymphoma)
  • Non-Hodgkin lymphomas (hairy cell leukemia and others).

Leukopenia due to severely reduced white blood cell count

Leukocytes go through different stages of development in the organism. The leukocytes find different names. The basic forms are granulocytopenia, also known as neutropenia, and lymphocytopenia.

It is well known that blood diseases have very different causes. Among them are cases in which the number of leukocytes has become dangerously low due to environmental factors. This applies in particular to contamination of the body with increased radioactive radiation or environmental toxins.

In addition, leukopenia is often the result of certain drug treatments. The occurrence of the disease after drug-based chemotherapy is known. Neuroleptics such as clozapine can also be the cause. Thiamazole, a drug used to regulate the thyroid in hyperthyroidism, may be a contributing factor.

leukocytopenia

Basically, doctors consider many blood and tissue diseases as the reason for this disease. Furthermore, ingested allergens are suspected of being associated with the occurrence of leukopenia.

This is particularly the case when the spleen is enlarged. Previous diseases such as measles, rubella or mumps are possible contributory causes of the disease. Such a strong reduction in granulocytes, as in leukopenia, is the consequence, particularly as a result of severe inflammation in the body.

leukopenia symptoms

Symptoms when there are too few leukocytes

If the number of white blood cells, known as leukocytes, is below the normal value, doctors speak of leukopenia. There are a variety of causes that cause a low concentration of white blood cells. In the case of leukopenia, it is mainly the granulocytes that decrease in number. Thus, if there are too few leukocytes, the symptoms initially appear as general signs of illness. If there is a reduced number of white blood cells in the organism, those affected suffer from an increased susceptibility to infections.

Summary of the symptoms of leukopenia

In the blood of leukopenia patients, the doctor finds a lower number of white blood cells than normal. For example, leukopenia occurs after a long-term infection because the body is unable to reproduce the leukocytes.

Due to the lack of white blood cells, there is a risk of a higher susceptibility to infection. In addition, too few leukocytes cause symptoms that are similar to general signs of illness. An example of an increased body temperature belongs in this area. The severity of the features depends on the duration of the leukopenia.

WBC count and symptoms are related

There are many reasons for a low white blood cell count. Viral infections mainly cause a temporary overproduction of leukocytes. As a result, there is no way for the organism to maintain the intensity of the formation of white blood cells over a longer period of time. This reduces the number of white blood cells. In this case, the leukopenia predominantly affects the granulocytes known as scavenger cells .

However, the concentration of granulocytes decreases at the same time when certain medications are administered. These are used, for example, in the course of chemotherapy. In order to stem the decline in granulocytes, doctors use active ingredients that stop leukopenia. In the study published by leucomax in 1998, the authors Feng and Zhou examined the rhGM-CSF factor. The aim was to treat cancer chemotherapy-induced leukopenia.

In addition to the causes of the low concentration of white blood cells, the resulting signs play a major role. As a rule, there is a close connection between too few leukocytes and the symptoms that arise as a result. The main focus is on the duration of the leukopenia.

If there is a short-term underproduction of white blood cells, the patients only suffer from weak characteristics. For example, they notice a slight fatigue. In addition, the low leukocyte count increases the susceptibility to infections. In some cases, patients feel feverish as inflammation builds up inside the body. As soon as the leukocytes reproduce, the symptoms decrease.

What are the signs of chronic leukopenia?

If the number of white blood cells falls permanently, the characteristics of the disease increase. The first symptoms include boils on the skin, which also indicate an inflammatory process within the organism. In addition, the lymph nodes of those affected swell noticeably, so that they feel hard when touched. Abscesses develop primarily in the area of ​​the mucous membranes. In the oral cavity of the sufferer, the doctor discovers:

  • periodontitis,
  • Stomatitis
  • and ulceration of the oral mucosa.

The inflammation of the gums and mucous membranes mainly occurs at the beginning of leukopenia. If there are fewer than 3,500 white blood cells in one microliter of blood, there is a severe undersupply of leukocytes. This makes the symptoms worse. Patients are increasingly suffering from sinusitis or otitis media (inflammation of the middle ear). Collateral angina, known as pharyngitis, also occurs at short intervals.

A symptom of leukopenia that affects the lungs is pneumonia. This is when pathogens enter the organ, causing an inflammatory reaction. If those affected are already weakened, the pneumonia can lead to death in the worst case.

Predominantly, neutrophilic granulocytes decrease

In the course of a decrease in white blood cells, the number of neutrophils primarily decreases. The doctors speak of neutropenia. Like the other forms of leukopenia, the disease is associated with specific symptoms. The risk of infection is of great importance. The more granulocytes are missing from the organism, the more pathogens get into the bloodstream.

The resulting disruption of the body’s immune system causes patients to develop bacterial and viral infections. To diagnose the leukopenia, the doctor uses a complete blood count . Here he can see at first glance whether the value of the white blood cells is low. With the help of a differential blood count, the doctor is able to find out which type of leukocytes is reduced.

The immune system does not reliably fight off bacteria. In the area of ​​the mouth, periodontitis and inflammation of the mucous membranes in the mouth are possible signs of recognition. Frequent and severe gingivitis, which can manifest itself in gum bleeding, is also particularly noticeable. As part of the increased susceptibility to infections, inflammation of the paranasal sinuses (sinusitis), inflammation of the middle ear (otitis media) and very painful inflammation of the pharynx often occur.

In more severe and acute cases, pneumonia is often the result. The skin may react to the disease with boils. These are painful excesses, which, however, can heal again with remaining scar tissue. These can appear on the entire thorax and on the groins, armpits and near the nose. Acute symptoms can also be fever or swelling of the lymph nodes.

Sequelae of leukopenia

The disease typically progresses rapidly. Therefore, many symptoms can also occur in other organs, since the deficiency may occur in the entire bloodstream. In general, leukopenia is diagnosed when there is an increased occurrence of symptomatic furuncles and chronic diseases of the respiratory tract and oral mucosa. In the case of an acute course, severe fever episodes are also a possible indication.

Leukopenia Diagnosis

To ensure the diagnosis, the doctor uses various diagnostic tools. First, a large blood count ordered by the doctor provides information about the number of leukocytes. The type of reduced leukocytes makes it clear which leukopenia is present.

The doctor examines the organs for possible subsequent symptoms of the disease. As already mentioned, he pays special attention to the size of the spleen and a possible expansion of the lymph node volume. A bone marrow biopsy is performed to definitively determine leukopenia.

leukopenia treatment

How can leukopenia be treated?

The disease manifests itself through a completely permeable immune system (similar to that of an HIV infection). Therefore, the patient must be shielded from external pathogens and viruses as best as possible.

Traditionally, this used to take place in an isolation ward. Both the hospital staff and visitors entered the patient’s room wearing only protective clothing and, in some cases, the air they breathed was filtered. This complete shielding is no longer common today. Rather, the doctor tries to substitute the immune activity with the administration of antibiotics.

Furthermore, in certain forms of leukopenia, the patient receives medication that increases the number of blood cells. Of these so-called hematopoietic growth factors, G-CSF is the most commonly used. It is particularly effective in neutropenia because it stimulates the formation of granulocytes.

Overall, with all types of leukopenia, compliance with hygiene regulations and special caution when dealing with physical contact must be observed. Targeted treatment of leukopenia, which has become established over the past 20 years, has reduced the mortality rate to around 5%.

General information and root cause analysis

The overall mechanisms that can lead to drug-induced leukopenia are still controversial. Some well-known pain relievers such as diclofenac, ibuprofen and especially Novalgin are under discussion as causes. With a differentiated diagnosis of a form of leukopenia, these potentially causative agents are replaced with harmless ones.

In the field of geriatrics, a mostly severe course is documented. This is due, for example, to the fact that older people are increasingly taking larger amounts of different drugs, which makes it difficult to identify a specific drug as the trigger.

With a differentiated diagnosis and targeted treatment of the symptoms, leukopenia is reversible. The risk of a new illness can be minimized for the future, for example by replacing the potentially causative medication or stabilizing the immune system.

Sources

  • Dietrich Reinhardt, Thomas Nicolai, Klaus-Peter Zimmer: Therapy of diseases in childhood and adolescence. 9th edition. Heidelberg: Springer Verlag (2014). ISBN-10: 3642418139.
  • Reinhard Andreesen, Hermann Heimpel: Clinical hematology. Munich 2009: Urban & Fischer/Elsevier-Verlag. ISBN-10: 343731498X.
  • Marlies Michl: BASICS Hematology. Munich 2016: Urban & Fischer/Elsevier-Verlag. ISBN-10: 3437421697.
  • Kurt Possinger, Anne Constanze Regierer: Specialist knowledge in hematology and oncology. 3. Edition. Munich 2015: Urban & Fischer/Elsevier-Verlag. ISBN-10: 3437212133.
  • Helga Donath: Internal medicine. Textbook for Nursing and Studies. 7th edition. Stuttgart 1993: Schattauer-Verlag. ISBN-10: 3794514963.

About Christina Jourdan

Welcome to my blog LeukocytesGuide dedicated to providing information about leukocytes, their functions, and diseases related to them. My name is Christina Jourdan, and I am a healthcare professional with extensive experience in the field of immunology. My passion for leukocytes began during my undergraduate studies, where I was fascinated by their role in the immune system. Leukocytes, also known as white blood cells, are an essential part of our body’s defense system. They protect us against infections and help us fight off harmful pathogens.

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