White blood cells make up our defense against foreign organisms and inner diseases, including autoimmune disease and cancer. They are produced by the bone marrow and have a lifespan of a few weeks. White blood cell count is flexible, and although it has a normal range of 4000-11000 per cubic milliliter, they can change their numbers and increase in response to infections, allergy or cancers. An increased number doesn’t mean that all is well, and a cause has to be sought. The same applies in decreased count, which is called leukopenia.
What can cause leukopenia?
Many causes can lead to a fall in white blood cell count. We will classify them according to the origin of such a low count:
Viral infections
Viral infections have different mechanisms to cause leukopenia. The mechanism depends on the type of virus and the organ it affects. For example, the most common viral infection associated to leukopenia is Epstein-Barr virus, which causes what we call infectious mononucleosis or “kissing fever”. It causes leukopenia through a strong immune response in the T- lymphocytes that are followed by a strong suppression. Epstein-Barr is not the only virus that causes leukopenia through this mechanism, however, and many others have the same mechanism, including herpes, cytomegalovirus, hepatitis C and even HIV.
Other mechanisms by which viruses cause leukopenia may be related to directly shutting down the bone marrow, which is the main manufacturing plant for white blood cells. The most famous is perhaps the Parvovirus B19. Others don’t just affect bone marrow nor on the immune system directly, but have some drug regimens that cause such a condition especially hepatitis C.
Some viruses can also cause cancers that affect white blood cell count negatively, Epstein-Barr virus is linked to many cancers, especially nasopharyngeal cancer, but cancer that causes leukopenia, in this case, is Hodgkin’s lymphoma. The mechanism by which lymphoma can cause leukopenia will be explained later in the article. Hepatitis C virus can also cause leukopenia through inducing acute myeloid leukemia.
Malnutrition and vitamin deficiencies
White blood cells, like all other cells, need proper nutrition to divide and differentiate, and any change of raw materials to produce them will cause a fall in their numbers. Protein malnutrition, which is usually found in poor countries or some vitamin deficiencies as vitamin B12, vitamin d and folic acid, and some minerals as zinc and copper are linked to leukopenia.
Congenital conditions
Some conditions present at birth may cause leukopenia, including infections transmitted from an infected mother such as HIV, or other genetic conditions such as Fanconi’s anemia, Schwachman-Diamond syndrome, severe congenital neutropenia, myelokathexis and Chediak-Higashi syndrome.
Cancers
Some cancers can cause leukopenia, especially if they involve the bone marrow. The most common culprit in acutely developing leukopenia is acute myeloid leukemia. When the diagnosis is suspected, acute myeloid leukemia patients should undergo a blood film analysis. This is a manual examination of the blood because the automated analyzer may falsely think that they have an elevated white blood cell count. The reason behind this is the presence of huge numbers of immature cells in their blood called blast cells. These cells invade the bone marrow and hinder the division and differentiation of other cells of the bone marrow causing deficiencies of all cells in the blood.
Another cancer that can cause the same problem is lymphoma. Lymphomas may also invade the bone marrow resulting in reduced formation of blood cells.
Autoimmune diseases
Autoimmune diseases have a common mechanism: the immune system goes mad and starts attacking the body cells. What is strange about these diseases is that sometimes the immune system targets cells of the immune system, including white blood cells, causing a fall in their numbers. This may be significant in some diseases, such as systemic lupus, where a decreased white blood cell count is considered an important criterion for the diagnosis.
Other autoimmune diseases associated to leukopenia are rheumatoid arthritis and Sjogren syndrome. What is even worse is that the treatment of such conditions starts with immune suppression, causing further deterioration of white blood cells in many cases.
Hypersplenism
Hypersplenism is a condition that results from many infectious and hematological conditions. It involves an abnormal enlargement of the spleen, and this organ starts eating up blood cells excessively and indiscriminately. This causes anemia, leukopenia and increased bleeding tendency because of decreased platelet count. The only option for such cases is the surgical removal of the spleen “splenectomy”. It causes a rapid resolution of the symptoms in most cases.
Drug-induced
Some drugs can cause a fall in the leukocyte count, especially neutrophils. Chemotherapy drugs are the most that can cause leukopenia, and it is dose-related. In other words, the higher the dose, the greater the effect on the number of cells. Other drugs can also affect leukocyte count, including antiepileptic drugs as lamotrigine, antibiotics as penicillin, vancomycin and trimethoprim-sulfamozxazole, antimalarials such as hydroxychloroquine, and even some thyroid medications as methimazole. It is worth noting, however, that the risk of having leukopenia due to non-chemotherapy drugs is minimal and much less compared to chemotherapy.
Granulomatous diseases
Granulomatous diseases are a large group of diseases which share in the process of forming granulomas. These are immune reactions against something foreign which take a specific globular shape of cells. Examples of such conditions include tuberculosis, sarcoidosis, leprosy and cat-scratch disease.
The mechanism by which such diseases can cause leukopenia is quite complex, and although some rare diseases exist where both conditions are independent, such as chronic granulomatous disease, the main mechanism of action in most cases is through the invasion of the bone marrow by such granulomas. In such a case, they act in a similar way to cancer.
Radiation
If you ever heard that a cancer patient received radiotherapy or radiation and wondered why? it is because ionizing radiation is lethal to cells. That’s why we limit the amount of radiation we expose patients to. This includes X-rays and CT scans. Radiation has an especially harmful effect on rapidly dividing cells, including hair cells, nails, skin, testes, ovaries and blood cells. That’s why leukopenia is a common finding in cancer patients exposed to radiation therapy or even in case of radiation sickness. A stark example of this was seen in survivors of the bombing of Hiroshima and Nagasaki, and those who lived in the vicinity of the Chernobyl reactor.
Symptoms of leukopenia
Leukopenia is not an independent entity, and by itself is usually symptomless. However, the cause of leukopenia may also give its own symptoms. Commonly associated symptoms include:
- Symptoms of infection: Infection is the commonest complication of leukopenia, and if you leave a treasure without a guardian, it will be stolen overnight. Your body will quickly catch an infection if your white blood cells fall rapidly. It is worth noting, however, that the symptoms of infection in such cases may be subtle owing to the fact that most symptoms are in fact a result of the immune system fighting disease rather than the disease itself. The fever, fatigue and sore throat that we feel is less due to the effect of the bacteria or the virus and more due to the crossfire that occurs between the immune system and these organisms.
- Enlarged lymph nodes: Enlarged lymph nodes are seen in many conditions that cause leukopenia, including cancers, granulomatous diseases and autoimmune diseases.
- Fatigue and breathlessness: They are not due to the leukopenia but the anemia that may be associated with leukopenia in infections, cancers, autoimmune diseases and some drugs especially chemotherapy.
- Enlarged spleen: The spleen may be enlarged, especially when it is the main cause of leukopenia, as in hypersplenism or if it is equally affected as in leukemias and lymphomas.
- Skin rash: Skin rash can be due to a multitude of causes, from bleeding into the skin due to deficiency of platelets to a manifestation of autoimmune diseases.
Should I be worried if I am diagnosed with leukopenia?
There are two factors to consider when you’re diagnosed with leukopenia. Firstly, the severity of the condition because a chronic low-grade leukopenia isn’t as severe as acute leukemia, and the risk of infection from the former is very low. The second factor is the cause of leukopenia, which is the main determinant of the outcome. A leukopenia due to a previous infection or malnutrition can be managed easily, and correction of the main problem is not challenging, while a leukopenia due to cancer or autoimmune diseases can prove troublesome both in treatment and complications of the original condition.