What to Know About Agranulocytosis

Medically Reviewed by Jabeen Begum, MD on August 25, 2022
Written by Parang Mehta
5 min read

Granulocytes are white blood cells that contain granules. There are three types — neutrophils, basophils, and eosinophils. These granules contain enzymes that enable these cells to kill bacteria and other disease-causing organisms. Granulocytes are formed in the bone marrow and are a vital part of the body's immune defense. 

Agranulocytosis is a reduction in the number of granulocytes in the blood. It leaves you susceptible to infections and can lead to frequent, dangerous infectious diseases.

Among the granulocytes, the most abundant cells are the neutrophils. These cells play an important role in defending against infections. Agranulocytosis is diagnosed based on the neutrophil count.

Granulocytes are a vital part of your body's infection defense. Not having enough in the blood places you at risk of infections. Once the white blood cells are less than 500 per microliter, the risk of infections is drastically increased. Resulting infections frequently affect the skin, mouth and throat, lungs, anal canal, or vagina, but other organs can also be involved.

Agranulocytosis is the severe reduction of granulocytes in the circulating blood. It is a more severe form of neutropenia, a condition that involves low numbers of white blood cells. People over 10 years old with less than 1,800 white blood cells per microliter of blood are said to have neutropenia. When the count falls below 500 per microliter, that is agranulocytosis. 

The two agranulocytosis types are congenital and acquired. Congenital agranulocytosis is caused by genetic disorders. Infantile genetic agranulocytosis, also called congenital agranulocytosis or Kostmann syndrome, affects how the bone marrow produces white blood cells. Children with this rare inherited disorder have frequent fevers, infections, and bone problems. 

Other conditions causing agranulocytosis in childhood are the Shwachman-Diamond syndrome, congenital amegakaryocytic thrombocytopenia, ataxia-pancytopenia, Dubowitz syndrome, reticular dysgenesis, and Seckel syndrome. Many of these disorders necessitate bone marrow transplantation to correct the agranulocytosis.

Acquired agranulocytosis happens later in life and can be caused by:

  • Medicines
  • Infections
  • B12 deficiency
  • Folate deficiency
  • Alcohol dependency
  • Anorexia nervosa.
  • Bone marrow diseases
  • Bone marrow transplants
  • Autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis

Medicines are the most frequent cause of acquired agranulocytosis. Many types of medicines can cause the bone marrow to stop making granulocytes. Others cause increased destruction of granulocytes, depleting their numbers.

Some medicines have a marrow-suppressing action and cause neutropenia or agranulocytosis in every person taking them. Others are safe in most people but cause marrow suppression in a few people:

  • Medicines working through the immune system. These drugs create antibodies that attack the granulocytes. Antithyroid drugs, quinidine, and certain drugs used in chemotherapy appear to cause agranulocytosis by this mechanism.
  • Medicines suppressing the bone marrow. These drugs interfere with granulocyte colony formation in the bone marrow. Some drugs that do this are valproic acid, carbamazepine, and beta-lactam antibiotics (such as amoxicillin). 
  • Medicines destroying granulocyte precursors, special cells that would mature into granulocytes in the bone marrow. Such medicines include phenytoin, methotrexate, cytarabine, and pyrimethamine. 
  • Anti-cancer drugs and anti-psychotic drugs. These drugs often cause agranulocytosis, making treatment of the original condition difficult.
  • Anti-inflammatory drugs such as aminopyrine, phenylbutazone, and salazopyrine.

Several infections can affect the bone marrow and suppress white cell production:

Agranulocytosis is often discovered when a blood test is done for another reason. It often has no symptoms of its own but leaves you susceptible to infections. These infections cause symptoms such as:

  • Fever
  • Chills and shivering
  • Mouth ulcers
  • Headache
  • Sweating
  • Swollen lymph nodes
  • Liver or spleen enlargement
  • Tiredness

Infections can progress rapidly to sepsis, a dangerous disorder characterized by widespread infection and a fall in blood pressure. The body is unable to fight the infecting organisms, and there are widespread metabolic abnormalities. Mortality is high.

Agranulocytosis is more likely to cause dangerous sepsis in people over 65. People with agranulocytosis and other health problems like kidney disease or heart disease are also more likely to have severe complications.  

The treatment of agranulocytosis should always begin with a diligent search for the cause. Removing or treating the cause is crucial to treating this dangerous condition. Agranulocytosis caused by medicines usually reverses 2 to 3 weeks after the medicine is stopped.

Treatment of agranulocytes is aimed at:

Stimulating the production of white blood cells. Your doctor may treat you with filgrastim, a drug used to treat severe, long-lasting neutropenia. This drug stimulates the formation and proliferation of neutrophils. Other agents being tried are colony-stimulating factors that stimulate the production of granulocytes. 

Treating any infections. If you have a bacterial infection because of agranulocytosis, your doctor will prescribe antibiotics to cure it. You may need antiviral or antifungal medicines if you have such infections. Your doctor will usually prescribe antibiotics for 7 to 10 days. You may have to take low-dose antibiotics by mouth for a prolonged period to avoid infections, but this can lead to infections by antibiotic-resistant bacteria or opportunistic organisms like cytomegalovirus.  

Infections can rapidly increase in severity. If you have an infection, your doctor may hospitalize you to give intensive treatment with intravenous injections. 

Your doctor may advise a bone marrow transplant if agranulocytosis persists. You will receive bone marrow from a matched donor so that you can produce white blood cells.

If you have agranulocytosis, you are at high risk of catching any infection to which you are exposed. Infections are the chief complication of this disorder, and their occurrence depends on its duration and its severity. People whose neutrophil count stays below 100 per microliter for more than 3 or 4 weeks have an almost 100% incidence of infection.

Some precautions can help you stay safe, though:

  • Eat only well-cooked food. Avoid salads, sauces, and undercooked or raw food like meat, shellfish, and eggs.
  • Store and prepare food carefully.
  • Avoid going to crowded places.
  • Only eat fruits and vegetables that can be thoroughly washed or peeled.
  • Avoid working with soil and animals.
  • Wash hands frequently and maintain good personal hygiene.
  • Use an electric shaver instead of razors.
  • Don't swim in ponds and rivers and avoid shared hot tubs.
  • Avoid close contact with sick people.

Agranulocytosis is a dangerous condition and can cause severe, life-threatening infections. Your doctor will try to find the cause, but many causes of agranulocytosis are reversible. 

Watch out for the signs of agranulocytosis if you know you have a condition associated with it. Your doctor will warn you before prescribing any medicines known to cause agranulocytosis. 

If you are affected by this disorder, treating infections early is vital to prevent them from escalating out of control. Alertness for signs of infection and quick action can save you from complications and life-threatening situations.