Leukopenia

Leukopenia - What is Leukopenia?

White blood cells are the soldiers that constitute the immune system of the human body. In leukopenia there is a diminished white blood cell count. When this happens, the immunity is severely weakened and the individual is at a greater risk of infections. Leukopenia may be caused by diseases, medications, and genetic deficiencies.

White blood cells

White blood cells are also termed leukocytes. The Greek word ‘leuko’ means white and ‘cyte’ means cell. Normally there are around 7000 white blood cells per microliter of blood. This forms around 1% of the total blood volume in healthy adult individuals. A decrease below the lower limit is called leukopenia.

Leukocyte classification

Leukocytes are classified according to the presence of granules within them. The ones with granules are the granulocytes while the ones without are the agranulocytes.

Granulocytes

Granulocytes are also called polymorphonuclear leukocytes. These possess granules which are actually membrane-bound enzymes acting on the invading organisms that have been engulfed by the cell.

There are three types of granulocytes that are named according to their staining properties:

  • neutrophils
  • basophils
  • eosinophils

Agranulocytes

Agranulocytes are also called mononuclear leukocytes and do not have granules in their cytoplasm. These contain some azurophilic granules, which are actually lysosomes that help in killing the invading organism. The cells include lymphocytes, monocytes, and macrophages.

Leukopenia forms

The most common form of leukopenia is neutropenia. Normally Neutrophils comprise about 45 to 75 percent of the total white blood cell count. These are the most important initial fighters of the immune system. They are responsible for fighting bacterial, fungal, viral, and parasitic infections.

Neutropenia raises the risk of bacterial infections. If the condition is not treated early this may lead to life threatening infections, septic shock and even death.

Diagnosis of leukopenia and neutropenia

A complete blood count helps in diagnosis of leukopenia and neutropenia. Neutropenia in adults is defined as an absolute neutrophil count of less than 500 cells per microliter (µL) of blood. Counts less than 1000 cells/µL are dangerous and may raise the risk of infections.

Management of leukopenia

Treatment of leukopenia depends on the cause of the condition. For example, if there is a bone marrow suppression due to medications like anti-cancer chemotherapy, stopping the drug may often cause recovery in the white blood cell counts.

Neutropenia is also associated with radiation treatment affecting the bone marrow. Once the therapy is stopped the counts may recover. Leukopenia caused due to bacterial or fungal infections may be treated with appropriate antibiotics and antifungals respectively.

Those with genetic conditions leading to leukopenia may need granulocyte colony-stimulating factor and other bone marrow–derived growth factors to stimulate production of the WBCs.

Leukopenia Causes

Leukopenia refers to the decrease in the number of white blood cells (WBC) in blood. This may be caused due to certain medications, chemotherapy for cancer, radiation therapy for cancer, surgery, stem cell transplant, bone marrow transplant, steroids, cancer itself, some genetic conditions as well as autoimmune diseases. This is called immunosuppression as leukopenia leads to a weakened immunity.

Normal WBC counts

Leukopenia is caused due to decrease in number of WBCs, particularly neutrophils. For normal adult males the WBC counts range between 4500 and 11000 per cubic millimetre of blood. This is slightly higher in children.

Causes of Leukopenia

Leukopenia may be caused by various diseases and drugs. Some of these are outlined here:-

Bone marrow damage or suppression

This is caused due to exposure to certain chemicals or toxins, cancer chemotherapy, radiation therapy and certain drugs. These agents cause a decrease in production of all the cells of the bone marrow leading to leukopenia, anemia (low number of red blood cell production and platelets).

Bone marrow diseases

In these conditions the bone marrow does not produce sufficient WBCs or selectively produces excess of one type of WBCs leading to a lack of other types. The causes include myelodysplastic syndrome, leukemia, myeloproliferative syndrome, myelofibrosis (bone marrow replaced by fibrous tissues), vitamin B12 or folate deficiency etc.

Cancers that have spread to the bone marrow

Cancers when they have spread to the bone marrow may lead to leukopenia. This is seen in lymphomas and other cancers.

Autoimmune disorders

This occurs when the body fails to recognise its own cells and begins to attack them. In cases of leukopenia the body’s WBC’s are perceived as foreign and attacked. The condition is called lupus or Systemic lupus erythematosus (SLE).

Severe infections

Severe infections that deplete the body of WBCs may lead to leukopenia. This is called sepsis.

Diseases of the immune system

Diseases of the immune system, such as HIV, which destroy T lymphocytes

Hypersplenism

This is caused by enlargement of spleen that destroys the blood cells leading to leukopenia as well as anemia.

Other conditions

Other conditions like thyroid disorders (particularly over active thyroid glands), aplastic anemia, rheumatoid arthritis, parasitic infestations, vitamin deficiencies, mineral deficiencies of copper and zinc typhoid, malaria, influenza, dengue, Rickettsial infections, tuberculosis etc.

Pseudoleukopenia

This occurs at the initial phases of the infection. The leukocytes (predominately neutrophils) are responsible for the initial reaction to an infection. After an infection these cells gather around the margins of the blood vessels (marginalized) so that they can scan for the site of infection. Thus there is increased WBC production but it appears low from a blood sample, since the blood sample is of core blood and does not include the WBCs gathered to reach the site of infection.

Drugs causing leukopenia

Some drugs may lead to leukopenia. Medications which can cause leukopenia include:

  • clozapine, an antipsychotic medication
  • sodium valproate and lamotrigine - antiepileptic agents
  • immunosuppressive drugs, such as sirolimus, mycophenolate mofetil, tacrolimus, and cyclosporine that are used in transplant patients
  • interferons used in treatment of multiple sclerosis etc.

The antidepressant and smoking addiction treatment medication called Bupropion and antibiotic Minocycline and penicillin may also cause leukopenia.

The mechanism of leukopenia caused by drugs is mainly mediated by the immune system itself. Some agents like cancer chemotherapy drugs however cause leukopenia by suppressing the bone marrow.