granulocytes

Granulocytes are types of white blood cells (leukocytes) that are part of the immune system and help fight infections. Granulocyte transfusions are administered to patients with low neutrophil count (neutropenia) and refractory bacterial or fungal infection.

Granulocytes are immune cells with granules containing enzymes that are released during infections, as well as in allergic reactions and asthma, causing the symptoms associated with these conditions. The four types of granulocytes are neutrophils, basophils, mast cells, and eosinophils.

Granulocytes engulf the disease-causing bacteria or parasites and release enzymes that break down and kill them. They also release inflammatory proteins (cytokines) that signal to and recruit other immune cells to fight infection. Granulocytes start the inflammation process but are also involved in resolving the inflammation, and healing. Neutrophils are the most abundant immune cells and among the first to arrive at the site of injury or infection. Granulocytes are transfused when neutrophils are low and the infection does not respond to medications.

Granulocytes have a very short span of life and survive only for 6-8 hours in peripheral blood and for 1-2 days in the injured or infected tissue. The bone marrow continually produces granulocytes to maintain the necessary count and the numbers normally go up during infections or injury. In patients who have neutropenia for any reason, the capacity to fight infection is lower and the infection can spread and become life-threatening if it is not resolved with medications.

Granulocytes are collected from suitable healthy donors, by a process known as apheresis, in which the donor’s blood passes through a medical device and may take 4-5 hours. The device separates granulocytes by centrifugal process and the red blood cells, platelets, and plasma are infused back into the donor. A day prior to collection, the donor, with their consent, may be administered granulocyte colony-stimulating factor (G-CSF) and dexamethasone, a corticosteroid, to stimulate growth of new white cells and to prolong their life.

Granulocyte concentrates are usually heavily contaminated by red blood cells and must be matched for ABO group and Rh factor, and/or undergo red cell depletion process. The granulocytes are further irradiated to prevent the lymphocytes from dividing and attacking the recipient’s tissue and causing graft-versus host disease (GVHD). The collected granulocytes must be transfused as soon as possible because of their short shelf life. Granulocytes are transfused daily for 5 days or longer until the infection is resolved or neutrophil count remains above 500/uL for 48 hours.

• Granulocyte transfusion should not be used as first-line treatment or as a single agent to treat the infection. Granulocyte transfusion is an additional supportive therapy intended for the management of infections that are not controlled by standard therapy.
• Granulocytes start losing function in 6 hours and expire in 24 hours. Screening the donor for infectious disease 1-2 days prior to collection and transfusion can provide the time required to ensure that the donor is negative for infectious diseases and is able to tolerate the apheresis process.
• Donors are most often administered granulocyte colony-stimulating factor (G-CSF) and a corticosteroid to increase granulocyte yield:
• Donors who have a history of diabetes, severe hypertension, cataracts, or peptic ulcer are generally not selected because of the potential side effects from corticosteroids.
• Donors should be screened for hemoglobinopathies such as sickle cell disease, a history of thrombosis or coronary artery disease, and inflammatory conditions such as uveitis. C-CSF should not be administered to donors with any of the above conditions.
• It is best to have multiple donors because of the necessity for daily collection and transfusion of granulocytes for several days until the infection is resolved.
• Granulocyte recipients may develop human leukocyte antigen (HLA) antibodies. Family members should be avoided as granulocyte donors if the recipient is a candidate for transplant. Family members are usually the optimal donors for transplants and the development of HLA antibodies can be a barrier for transplantation or accelerate graft failure, and may also lead to refractoriness to platelet transfusions.
• All granulocyte transfusions must be given using blood administration sets containing 170- to 260-micron filters or 20- to 40-micron microaggregate filters. Granulocytes must never be transfused via a leukocyte reduction filter.
• No other medications or fluids other than normal saline should be simultaneously given through the same line as granulocytes without prior consultation with the medical director of the blood bank.
• Monitor patients for signs of transfusion reaction, including vital signs, before, during, and after transfusion. If transfusion reaction is suspected, stop the transfusion, assess and stabilize the patient, and notify the blood bank to initiate an investigation.
• Granulocyte transfusion can cause severe pulmonary reactions if given concurrently with amphotericin antifungal medication. The two should be spaced as far apart as feasible.
• Granulocytes are usually heavily contaminated by red blood cells and must be matched for ABO group and Rh factor, and/or undergo the red cell depletion process.
• Granulocyte products have a large number of lymphocytes and must undergo irradiation to prevent graft-versus-host disease (GVHD). Patients most likely to require granulocyte transfusions are also at greater risk of GVHD due to their underlying condition.
• Cytomegalovirus (CMV) naive patients should receive CMV seronegative granulocytes since CMV is carried in white cells.
• Granulocyte transfusions carry the risk for non-septic infections including human immunodeficiency virus (HIV) hepatitis B and C viruses (HBV and HCV), human T-lymphotropic virus (HTLV), cytomegalovirus (CMV), West Nile virus (WNV), parvovirus B19, Lyme disease, babesiosis, malaria, Chagas disease and variant Creutzfeldt-Jakob disease (vCJD).
• Consult with the blood bank medical director or a hematologist if you have questions regarding special transfusion requirements.

Common side effects of granulocytes include:

• Fever
• Chills
• Allergic reactions such as:
  • Hives (urticaria)
  • Itching (pruritus)
  • Wheezing
  • Shortness of breath (dyspnea)
  • Low blood pressure (hypotension)
• Serious allergic (anaphylactic) reactions including:
  • Swelling under the skin and mucous membrane (angioedema)
  • Respiratory distress
  • Shock
• Hemolytic transfusion reactions that destroy red blood cells 
• Feverish (febrile) non-hemolytic reactions
• Transfusion-associated circulatory overload (TACO)
• Transfusion-related acute lung injury (TRALI)
• Transfusion-associated graft-versus-host disease (TA-GVHD)
• Transfusion-transmitted infections and septic reactions
• Post-transfusion bruising (purpura)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Neutropenia and Refractory Bacterial or Fungal Infection

Adult:

• The standard dose in adults is one apheresis unit per day (300-400 mL). The number of granulocytes per dose can vary greatly (from 1-8 x 1010 granulocytes/collection) based on the donor and mobilization regimen given to the donor. Granulocytes are typically transfused daily for 5 or more consecutive days and should be continued until the infection resolves or the absolute neutrophil count remains above 500/uL for 48 hours.

Pediatric:

• Infants and small children should receive 1-2 x 109 granulocytes/kg per day. The volume will vary based on granulocyte concentration of the donor but usually ranges from 10-20 mL/kg.
• Larger children can be dosed as an adult and receive one full apheresis unit per day.
• Granulocytes are typically transfused daily for 5 or more consecutive days and should be continued until the infection resolves or the absolute neutrophil count remains above 500/uL for 48 hours.

Other Information and Uses

• The decision to transfuse granulocytes should be made in consultation with the transfusion medicine physician because of a lack of established efficacy in randomized controlled trials and the coordination required to provide granulocytes as they must be collected on the day of transfusion.
• Neutropenia (below 500 PMNs/uL) and documented refractory bacterial or fungal infection failing to respond to appropriate antimicrobial therapy for more than 24 to 48 hours may be considered for granulocyte transfusion if the neutropenia is due to reversible myeloid hypoplasia.
• Congenital neutrophil defects (i.e., chronic granulomatous disease) and documented refractory bacterial or fungal infection failing to respond to appropriate antimicrobial therapy for more than 24 to 48 hours may be considered for granulocyte transfusion.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Granulocytes have no known interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Cytomegalovirus-seronegative donors should be used for pregnant women who are CMV-seronegative or whose CMV status is unknown.
• Nursing mothers undergoing granulocyte transfusion should check with their physician before breastfeeding.