Granulocyte transfusion

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A granulocyte transfusion is a medical procedure in which granulocytes (a type of white blood cell) are infused into a person's blood. Granulocyte transfusions were historically used to prevent and treat infections in people with neutropenia (an abnormally low level of neutrophils), but the practice declined in popularity in the 1980s. Interest in the procedure increased in the 1990s due to the development of more effective methods for harvesting granulocytes and a growing population of people with severe neutropenia from chemotherapy. However, the treatment's efficacy remains poorly understood and its use is controversial. [1] [2] [3]

Contents

Granulocytes are most often collected through leukapheresis, a process that separates the donor's white blood cells from their red blood cells and plasma. Donors may be given corticosteroids or granulocyte colony-stimulating factor to increase their granulocyte count prior to the blood collection. Granulocytes have a short shelf life and it is recommended that they are transfused within hours of collection. Adverse effects from granulocyte transfusions include fever, chills, respiratory symptoms, transfusion-transmitted infections, and the development of antibodies against human leukocyte antigens, which can interfere with subsequent transfusions. [1]

Medical uses

A neutrophil seen in a blood smear Hem1SegmNeutrophile2.jpg
A neutrophil seen in a blood smear

Granulocytes are a category of white blood cells that includes neutrophils, eosinophils, and basophils. [4] : 99  Neutrophils are the most common type of granulocyte in normal blood, [5] : 82  and they play a major role in defending against infections, especially those caused by fungi and bacteria. [6] People with severe neutropenia, a low neutrophil count, have an increased risk of developing serious infections. One of the approaches to preventing and treating infections in people with neutropenia is to increase the neutrophil count, which is commonly done using drugs like G-CSF that stimulate the production of neutrophils in the bone marrow. [6] However, another approach is to directly transfuse granulocytes from a donor into the person's blood. [1]

As of 2015, there is some evidence that granulocyte transfusions may help to prevent bacteremia and fungemia in adults who have neutropenia caused by chemotherapy or hematopoietic stem cell transplantation. However, it is unclear whether this has any impact on mortality or major adverse events, [7] and the use of granulocyte transfusions to prevent infections is considered controversial because of the potential for serious side effects. [1] Although the studies performed to date have been low-quality, a 2016 review suggested that granulocyte transfusion may not be effective for treating infections in adults with neutropenia. [8] In both cases, the treatment is considered investigational. [7] [8]

Granulocyte transfusion is still used in some cases, such as when a person has severe neutropenia and an infection that is life-threatening or does not respond to antimicrobial treatment. [1] The treatment has also been studied in people with aplastic anemia (a condition in which a person's bone marrow does not produce enough blood cells) and chronic granulomatous disease (a disorder in which a person has a normal number of neutrophils, but they do not function correctly). Newborn babies who have neutropenia and sepsis are sometimes given granulocyte transfusions, [1] although a 2011 study found that there was insufficient evidence to determine whether or not this practice is effective. [9]

Donation

Prior to donating granulocytes, potential donors must undergo screening and testing procedures. They are required to meet the general criteria for blood donation. [1] Because the granulocyte concentrate also contains red blood cells, the donor's ABO blood type is usually matched to the recipient's. [note 1] If the recipient has antibodies against human leukocyte antigens (HLA), proteins found on the surface of white blood cells, the donor's cells need to be tested for compatibility, because antibodies against donor granulocytes can reduce the effectiveness of the transfusion and cause transfusion reactions. [10] : 630 

In order to collect enough granulocytes for the transfusion to be effective, donors are frequently given drugs to increase their neutrophil count prior to the blood collection. The treatment typically includes corticosteroids or G-CSF, often in combination. Before effective techniques were developed for increasing the neutrophil count and isolating granulocytes from other blood cells, granulocytes were sometimes collected from people with chronic myeloid leukemia, a disease that causes a very high neutrophil count. [2] [10] : 627  Donors may experience minor side effects from steroid and G-CSF treatment, including headaches, bone and joint pain, insomnia and fatigue. [1] During the blood collection, the donor's blood is mixed with hydroxyethyl starch, which helps separate the granulocytes from other blood components during sample processing. [1] [11] : 297 

The donor blood undergoes leukapheresis, a process by which white blood cells are separated from red blood cells and plasma. The other components of the blood are returned to the donor's circulation. [11] : 297  The process of collecting the granulocytes takes about four to five hours. [1] Because a large amount of blood (seven to ten litres) is processed during apheresis, donors may experience adverse effects from changes in fluid balance. [3] An alternative approach, more commonly used in the United Kingdom, is to combine the buffy coats (the fraction of blood containing white blood cells) from multiple routine blood donations to create a blood product containing a high amount of granulocytes. [12]

Once collected, granulocytes have a 24-hour shelf life. [12] It is recommended that they are transfused within a few hours of collection. [1] They cannot be frozen, as this severely inhibits the cells' functions. [10] : 628  The white blood cell concentrate obtained through leukapheresis contains a high number of active T lymphocytes, which can cause graft-versus-host disease in the recipient, so it is often exposed to radiation to inactivate these cells. [10] : 628 

Risks

Adverse effects are more common with granulocyte transfusions than with red blood cell transfusions. 25 to 50 percent of people who receive granulocyte transfusions experience mild to moderate side effects, while 1 percent experience severe complications. [1] Fever and chills are common side effects. [1] [2] Granulocyte transfusions may affect the lungs, causing cough, difficulty breathing, low oxygen levels, and abnormal chest X-rays. [1] These lung complications may potentially be fatal. [2] A review paper found that the frequency of lung-related side effects ranged from 0 to 53 percent. [13]

Recipients can develop transfusion-transmitted diseases if pathogens are present in the donor blood, which is a particular problem with granulocyte transfusions because of their short shelf life, which means they must be transfused before infectious disease testing is complete. [1] Infection with cytomegalovirus (CMV) is a concern, as this virus is found in white blood cells, so if the recipient is at risk of developing severe disease from CMV, it is recommended that granulocytes be collected from a CMV-negative donor. [2]

If the donor white blood cells are not irradiated, the recipient may be at risk of developing graft-versus-host disease. Finally, people who receive granulocyte transfusions may develop antibodies against the human leukocyte antigens found on the surface of white blood cells, which can predispose them to transfusion reactions, decrease the lifespan of donor white blood cells in their circulation, and reduce the efficacy of platelet transfusions and allogeneic stem cell transplants. [1] [2]

History

In a 1934 experiment, Strumia gave neutropenic patients intramuscular injections of neutrophils, but this proved ineffective in improving their neutrophil function. [14] [15] In 1953, Brecher et al. demonstrated the principle behind granulocyte transfusion by infusing neutrophils into dogs and showing that they travelled to sites of inflammation. [16] The first human granulocyte transfusions were carried out in the 1960s, using white blood cells harvested from people with chronic myeloid leukemia and concentrated using centrifugation. Steroid treatment and leukapheresis were later introduced, allowing granulocytes to be collected from healthy donors. However, these techniques were not very effective as they did not produce a high granulocyte count. Owing to poor efficacy, an undesirable side effect profile, and the impracticality of storing granulocytes for an extended period of time, the use of granulocyte transfusions declined. [3] Improvements in antimicrobial therapy and supportive care also played a role in the treatment's decreasing popularity. [1] However, the introduction of donor treatment with G-CSF in the 1990s allowed high numbers of granulocytes to be collected from healthy donors. This, combined with an increasing number of people with severe neutropenia as a result of chemotherapy and the growing prevalence of multidrug resistant infections, led to a renewal of interest in granulocyte transfusions. [3]

Notes

  1. ↑ If an ABO-compatible donor cannot be found, the granulocytes can undergo further processing to remove red blood cells. [10] : 630 

Related Research Articles

<span class="mw-page-title-main">Blood transfusion</span> Intravenous transference of blood products

Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but modern medical practice commonly uses only components of the blood, such as red blood cells, white blood cells, plasma, platelets, and other clotting factors.

Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count and thus causing neutropenia in the circulating blood. It is a severe lack of one major class of infection-fighting white blood cells. People with this condition are at very high risk of serious infections due to their suppressed immune system.

<span class="mw-page-title-main">Neutropenia</span> Abnormally low concentration of neutrophils (a type of white blood cell) in the blood

Neutropenia is an abnormally low concentration of neutrophils in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood. People with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening.

<span class="mw-page-title-main">Neutrophilia</span> Medical condition

Neutrophilia is leukocytosis of neutrophils, that is, a high number of neutrophils in the blood. Because neutrophils are the main type of granulocytes, mentions of granulocytosis often overlap in meaning with neutrophilia.

Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. The risk is especially high in cytotoxic chemotherapy for leukemia.

<span class="mw-page-title-main">Granulocyte colony-stimulating factor</span> Mammalian protein found in Homo sapiens

Granulocyte colony-stimulating factor, also known as colony-stimulating factor 3, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.

<span class="mw-page-title-main">Granulocyte</span> Category of white blood cells

Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They have varying shapes (morphology) of the nucleus ; and are referred to as polymorphonuclear leukocytes. In common terms, polymorphonuclear granulocyte refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types have varying morphology. Granulocytes are produced via granulopoiesis in the bone marrow.

<span class="mw-page-title-main">Apheresis</span> Medical techniques to separate one or more components of blood

Apheresis is a medical technology in which the blood of a person is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation. It is thus an extracorporeal therapy.

<span class="mw-page-title-main">Leukopenia</span> Medical condition

Leukopenia is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of infection.

Cytopenia is a reduction in the number of mature blood cells. It commonly occurs in people with cancer being treated with radiation therapy or chemotherapy.

Leukapheresis is a laboratory procedure in which white blood cells are separated from a sample of blood. It is a specific type of apheresis, the more general term for separating out one particular constituent of blood and returning the remainder to the circulation.

Cyclic neutropenia (CyN) is a rare hematologic disorder and form of congenital neutropenia that tends to occur approximately every three weeks and lasting for few days at a time due to changing rates of neutrophil production by the bone marrow. It causes a temporary condition with a low absolute neutrophil count and because the neutrophils make up the majority of circulating white blood cells it places the body at severe risk of inflammation and infection. In comparison to severe congenital neutropenia, it responds well to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count, shortens the cycle length, as well decreases the severity and frequency of infections.

<span class="mw-page-title-main">Fludarabine</span> Chemical compound

Fludarabine is a purine analogue and antineoplastic agent. It is generally used as its 5-O-phosphorylated form known as fludarabine phosphate, sold under the brand name Fludara among others. It is a chemotherapy medication used in the treatment of leukemia and lymphoma. These include chronic lymphocytic leukemia, non-Hodgkin's lymphoma, acute myeloid leukemia, and acute lymphocytic leukemia. It is given by injection into a vein or by mouth.

<span class="mw-page-title-main">Febrile neutrophilic dermatosis</span> Medical condition

Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is a skin disease characterized by the sudden onset of fever, an elevated white blood cell count, and tender, red, well-demarcated papules and plaques that show dense infiltrates by neutrophil granulocytes on histologic examination.

<span class="mw-page-title-main">Transfusion-related acute lung injury</span> Medical condition

Transfusion-related acute lung injury (TRALI) is the serious complication of transfusion of blood products that is characterized by the rapid onset of excess fluid in the lungs. It can cause dangerous drops in the supply of oxygen to body tissues. Although changes in transfusion practices have reduced the incidence of TRALI, it was the leading cause of transfusion-related deaths in the United States from fiscal year 2008 through fiscal year 2012.

<span class="mw-page-title-main">WHIM syndrome</span> Medical condition

WHIM syndrome is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia.

Febrile neutropenia is the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes in the blood. The term neutropenic sepsis is also applied, although it tends to be reserved for patients who are less well. In 50% of cases, an infection is detectable; bacteremia is present in approximately 20% of all patients with this condition.

Autoimmune neutropenia (AIN) is a form of neutropenia which is most common in infants and young children where the body identifies the neutrophils as enemies and makes antibodies to destroy them.

<span class="mw-page-title-main">White blood cell</span> Type of cells of the immunological system

White blood cells, also called leukocytes or leucocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells include three main subtypes; granulocytes, lymphocytes and monocytes.

<span class="mw-page-title-main">Toxic vacuolation</span> Inflammatory change in neutrophils

Toxic vacuolation, also known as toxic vacuolization, is the formation of vacuoles in the cytoplasm of neutrophils in response to severe infections or inflammatory conditions.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Goldfinger, D; Lu, Q (24 Jan 2020). "Granulocyte transfusions". UpToDate . Retrieved 27 May 2020.
  2. 1 2 3 4 5 6 Gea-Banacloche, Juan (2017). "Granulocyte transfusions: A concise review for practitioners". Cytotherapy. 19 (11): 1256–1269. doi:10.1016/j.jcyt.2017.08.012. ISSN   1465-3249. PMC   5716890 . PMID   28916227.
  3. 1 2 3 4 Klein K; Castillo B (2017). "Historical Perspectives, Current Status, and Ethical Issues in Granulocyte Transfusion". Ann Clin Lab Sci. 47 (4): 501–507. PMID   28801379.
  4. ↑ Bain, BJ (20 January 2015). Blood Cells: A Practical Guide. John Wiley & Sons. ISBN   978-1-118-81733-9.
  5. ↑ Barbara J. Bain; Imelda Bates; Mike A Laffan (11 August 2016). Dacie and Lewis Practical Haematology E-Book. Elsevier Health Sciences. ISBN   978-0-7020-6925-3.
  6. 1 2 Territo, M (July 2018). "Neutropenia – Hematology and Oncology". Merck Manuals Professional Edition. Archived from the original on 22 July 2019. Retrieved 28 May 2020.
  7. 1 2 Estcourt, Lise J; Stanworth, Simon J; Doree, Carolyn; Blanco, Patricia; Hopewell, Sally; Trivella, Marialena; Massey, Edwin (2015). "Granulocyte transfusions for preventing infections in people with neutropenia or neutrophil dysfunction". Cochrane Database of Systematic Reviews. 2018 (6): CD005341. doi:10.1002/14651858.CD005341.pub3. ISSN   1465-1858. PMC   4538863 . PMID   26118415.
  8. 1 2 Estcourt, Lise J; Stanworth, Simon J; Hopewell, Sally; Doree, Carolyn; Trivella, Marialena; Massey, Edwin (2016). "Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction". Cochrane Database of Systematic Reviews. 4 (7): CD005339. doi:10.1002/14651858.CD005339.pub2. ISSN   1465-1858. PMC   4930145 . PMID   27128488.
  9. ↑ Pammi, Mohan; Brocklehurst, Peter (2011). "Granulocyte transfusions for neonates with confirmed or suspected sepsis and neutropenia". Cochrane Database of Systematic Reviews. 2011 (10): CD003956. doi:10.1002/14651858.CD003956.pub2. ISSN   1465-1858. PMC   7104253 . PMID   21975741.
  10. 1 2 3 4 5 Harvey G. Klein; David J. Anstee (3 February 2014). Mollison's Blood Transfusion in Clinical Medicine. John Wiley & Sons. ISBN   978-1-4051-9940-7.
  11. 1 2 Denise M Harmening (30 November 2018). Modern Blood Banking & Transfusion Practices. F.A. Davis. ISBN   978-0-8036-9462-0.
  12. 1 2 West, Kamille A.; Conry-Cantilena, Cathy (2019). "Granulocyte transfusions: Current science and perspectives". Seminars in Hematology. 56 (4): 241–247. doi:10.1053/j.seminhematol.2019.11.002. ISSN   0037-1963. PMID   31836030.
  13. ↑ Yoshihara, Satoshi; Ikemoto, Junko; Fujimori, Yoshihiro (2016). "Update on granulocyte transfusions". Current Opinion in Hematology. 23 (1): 55–60. doi:10.1097/MOH.0000000000000203. ISSN   1065-6251. PMID   26554890. S2CID   29906057.
  14. ↑ Strumia, M.M. (1934). "The effect of leucocytic cream injections in the treatment of the neutropenias". American Journal of the Medical Sciences. 187 (4): 527–544. doi:10.1097/00000441-193404000-00010.
  15. ↑ Bishton, M.; Chopra, R. (2004). "The role of granulocyte transfusions in neutropenic patients". British Journal of Haematology. 127 (5): 501–508. doi: 10.1111/j.1365-2141.2004.05221.x . ISSN   0007-1048. PMID   15566353. S2CID   24079521.
  16. ↑ Brecher, G.; Wilbur, K. M.; Cronkite, E. P. (1953). "Transfusion of Separated Leukocytes into Irradiated Dogs with Aplastic Marrows". Experimental Biology and Medicine. 84 (1): 54–56. doi:10.3181/00379727-84-20539. ISSN   1535-3702. PMID   13120934. S2CID   38034154.
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