Dosing and uses of neutrophils (granulocytes)
Neutropenia & Refractory Bacterial or Fungal Infection
The standard dose in adults is one apheresis unit per day (~300-400 mL). The amount 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 infection resolves or absolute neutrophil count remains >500/uL for 48 hours.
Other Information & Uses
Please read entire monograph if you are considering granulocyte transfusion.
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 the day of transfusion.
Neutropenia (<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.
Pediatric dosage forms and strengths
Neutropenia & Refractory Bacterial or Fungal Infection
Infants and small children should receive 1-2 x 109 granulocytes/kg per day. The volume will vary based on granulocyte concentration of 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 infection resolves or absolute neutrophil count remains >500/uL for 48 hours.
neutrophils (granulocytes) adverse (side) effects
Frequency not defined
Fevers, chills, and allergic reactions are not uncommon with granulocyte transfusions. Patients should be closely monitored during transfusion. Premedication with antihistamines, corticosteroids, and mild antipyretics such as acetaminophen may be considered to minimize mild reactions. If severe reactions such as marked dyspnea or hypotension occur the transfusion should be discontinued, the patient assessed and stabilized, the blood bank notified, and transfusion reaction investigation initiated.
Hemolytic Transfusion Reactions
Febrile Non-Hemolytic Reactions
Allergic Reactions ranging from urticaria to anaphylaxis
Septic Reactions
Transfusion Related Acute Lung Injury (TRALI)
Circulatory Overload
Transfusion Associated Graft Versus Host Disease
Postransfusion Purpura
If the reaction seems mild to moderate and you are uncertain about the best course of action, pause the transfusion and immediately page the transfusion medicine physician.
Warnings
Contraindications
Granulocyte transfusion is a supportive adjuvant therapy to manage infections uncontrolled by standard medical therapy and thus should not be used as first line treatment or as the sole treatment of infection.
Cautions
There have been reports of severe pulmonary reactions when given concomitantly with amphoterecin. Infusion of amphoterecin and granulocytes should be spaced as far apart as reasonably possible.
Granulocyte products typically contain a large amount of red blood cells and thus should be ABO and Rh compatible and require RBC crossmatching to be issued. Some institutions have policies and procedures in place to reduce the amount of RBCs enough to transfuse ABO incompatible units.
Granulocytes begin to lose function within 6 hours of collection and have an expiration of 24 hours after collection. This usually requires special consent by the physician and/or patient to receive units before all infectious disease testing is complete. Collection centers have various strategies to ensure product safety such as utilizing frequent platelet donors or getting infectious disease testing 1-2 days prior to collection to help ensure the likelihood that the donor will be negative at the time of collection and be able to tolerate a large blood volume process.
Often times granulocyte donors are friends and family of the recipient because of the commitment needed to be a granulocyte donor. Granulocyte donors are almost always given medication regimens to increase the circulating granulocyte counts to improve collection. Corticosteroids when given alone can achieve around 1 x 1010 PMNs/unit. More currently, donors are given a combination of G-CSF and corticosteroids improving yield to 4-8 x 1010 PMNs/unit. Because of the potential adverse effects of the steroids, donors who have a history of diabetes, severe hypertension, cataracts, or peptic ulcer are generally not selected as granulocyte donors. Since there were case reports of severe reactions, including deatch, in persons with sickle cell trait who were given G-CSF, donors are also required to be tested for hemoglobinopathy before administration of G-CSF. Likewise, donors with a history of thrombosis or coronary artery disease, and donors with inflammatory states such as uveitis may also be deferred from receiving G-CSF to prevent possible complications.
It is best to have multiple donors as collections/transfusion should occur daily until resolution of the infection. If the recipient is a candidate for transplantation, family members should be avoided as donors since family members are often optimal candidates for transplant donation and HLA sensitization prior to transplantation can either be a barrier to transplantation or cause accelerated graft failure. HLA sensitization may also lead to refractoriness to platelet transfusions.
Due to the large number of lymphocytes in granulocyte collections, all granulocyte units should be irradiated to prevent GVHD. Additionally, patients that are most likely to require granulocyte transfusions also are at greater risk of GVHD due to their underlying condition or due to the fact that many are related directed donations.
Granulocytes must never be transfused via a leukocyte reduction filter.
CMV naïve patients should receive CMV seronegative granulocytes since CMV is carried in white cells.
All transfusions must be given via blood administration sets containing 170- to 260-micron filters or 20- to 40-micron microaggregate filters. No other medications or fluids other than normal saline should be simultaneously given through the same line without prior consultation with the medical director of the blood bank.
Patient’s should be monitored for signs of a transfusion reaction including vitals pre, during, and post transfusion.
Non-septic infectious risks include transmission of HIV (~1:2 mill), HCV (~1:1.5 mill), HBV (1:300k), HTLV, WNV, CMV, parvovirus B19, lyme disease, babesiosis, malaria, chaga’s disease, vCJD.
Consult with blood bank medical director or hematologist if you have questions regarding special transfusion requirements.
Pregnancy and lactation
CMV-seronegative donors should be used for pregnant women who are CMV naïve or whose CMV status is unknown.
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of neutrophils (granulocytes)
Granulocytes begin to lose function by 6 hours after collection and expire 24 hours after collection.
Transfused viable granulocytes have normal chemotactic and phagocytic functions; however their effectiveness in controlling infection is variable.
Post transfusion WBC counts do not indicate therapeutic effectiveness and the patient’s clinical condition should be used to determine effectiveness.
Mechanism of action
Granulocytes play a major role in fighting bacterial and fungal infections.
