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.

• Gajic, Ognjen; Moore, S. Breanndan (2005). “Transfusion-Related Acute Lung Injury”. Mayo Clinic Proceedings. 80 (6): 766–770. doi:10.1016/S0025-6196(11)61531-0. PMID 15945528.
• U.S. Food and Drug Administration, Center for Biologics Evaluation and Research. Fatalities Reported to FDA Following Blood Collection and Transfusion: Annual Summary for Fiscal Year 2012. Bethesda, Md: U.S. Food and Drug Administration.

Incidents have also been reported with other blood products including “cryoprecipitate, granulocytes, intravenous immune globulin, allogeneic and autologous stem cells”.

• Cho MS, Modi P, Sharma S. Transfusion-related Acute Lung Injury. 2020 Jul 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID 29939623.

Signs and symptoms

It is often impossible to distinguish TRALI from acute respiratory distress syndrome (ARDS). The typical presentation of TRALI is the sudden development of shortness of breath, severe hypoxemia (O₂ saturation <90% in room air), low blood pressure, and fever that develop within 6 hours after transfusion and usually resolve with supportive care within 48 to 96 hours. Although low blood pressure is considered one of the important signs for diagnosing TRALI, in some cases high blood pressure can occur.

• Silliman, C. C.; Fung, Y. L.; Ball, J. B.; Khan, S. Y. (2009). “Transfusion-related acute lung injury (TRALI): Current Concepts and Misconceptions”. Blood Reviews. 23 (6): 245–255. doi:10.1016/j.blre.2009.07.005. PMC 3134874. PMID 19699017.

Delayed TRALI occurs 6 to 72 hours after transfusion completion. It is associated with a higher rate of mortality.

• Cho MS, Modi P, Sharma S. Transfusion-related Acute Lung Injury. 2020 Jul 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID 29939623

Cause

The cause of TRALI is currently not fully understood. 80–85% of cases are thought to be immune mediated. Antibodies directed toward human leukocyte antigens (HLA) or human neutrophil antigens (HNA) have been implicated, with transfused antibodies shown to bind antigens expressed on pulmonary endothelial cells to initiate acute inflammation in the lungs. Women who are multiparous (have carried more than one pregnancy to viable gestational age) develop these antibodies through exposure to fetal blood; transfusion of blood components obtained from these donors is thought to carry a higher risk of inducing immune-mediated TRALI. Previous transfusion or transplantation can also lead to donor sensitization. To be at risk of TRALI via this mechanism, the blood recipient must express the specific HLA or neutrophil receptors to which the implicated donor has formed antibodies. A two-hit hypothesis has been suggested wherein pre-existing pulmonary pathology (i.e., the first-hit) leads to localization of neutrophils to the pulmonary microvasculature. The second hit occurs when the aforementioned antibodies are transfused and attach to and activate neutrophils, leading to release of cytokines and vasoactive substances that induce non-cardiac pulmonary edema.

• “Transfusion-related acute lung injury (TRALI)”. Professional Education.
• Muller, J.Y. (2005). “Le TRALI : du diagnostic à la prévention” [TRALI: from diagnosis to prevention]. Transfusion Clinique et Biologique (in French). 12 (2): 95–102. doi:10.1016/j.tracli.2005.04.007. PMID 15894508. INIST 16924693.
• Cleary, Simon J.; Kwaan, Nicholas; Tian, Jennifer J.; Calabrese, Daniel R.; Mallavia, Beñat; Magnen, Mélia; Greenland, John R.; Urisman, Anatoly; Singer, Jonathan P.; Hays, Steven R.; Kukreja, Jasleen; Hay, Ariel M.; Howie, Heather L.; Toy, Pearl; Lowell, Clifford A.; Morrell, Craig N.; Zimring, James C.; Looney, Mark R. (5 October 2020). “Complement activation on endothelium initiates antibody-mediated acute lung injury”. Journal of Clinical Investigation. 130 (11): 5909–5923. doi:10.1172/JCI138136. PMC 7598054. PMID 32730229.
• Dykes, A.; Smallwood, D.; Kotsimbos, T.; Street, A. (June 2000). “Transfusion-Related Acute Lung Injury (Trali) In A Patient With A Single Lung Transplant: Correspondence”. British Journal of Haematology. 109 (3): 674–676. doi:10.1046/j.1365-2141.2000.01999.x. PMID 10886228. S2CID 42922617.
• Silliman, Christopher C. (2006). “The two-event model of transfusion-related acute lung injury”. Critical Care Medicine. 34 (5 Suppl): S124–131. doi:10.1097/01.CCM.0000214292.62276.8E. ISSN 0090-3493. PMID 16617256. S2CID 36068011.
• Harmening, Denise (2019). Modern Blood Banking & Transfusion Practices. Philadelphia: F.A. Davis Company. p. 381. ISBN 9780803668881.

A proposed mechanism for non-antibody-mediated TRALI involves the accumulation of bioactive lipids in stored blood components (red cells, platelets, or plasma) that are capable of priming neutrophils.

• Silliman, C. C.; Fung, Y. L.; Ball, J. B.; Khan, S. Y. (2009). “Transfusion-related acute lung injury (TRALI): Current Concepts and Misconceptions”. Blood Reviews. 23 (6): 245–255. doi:10.1016/j.blre.2009.07.005. PMC 3134874. PMID 19699017.

TRALI is typically associated with plasma products such as fresh frozen plasma. TRALI can also occur in recipients of packed red blood cells, whether adult or pediatric patients. Due to the higher risk of TRALI resulting from donations by females, the AABB (formerly the American Association of Blood Banks) has recommended that those blood components with a high volume of plasma not be used for transfusion, but for further processing into other therapeutic products.

• Cudilo, Elizabeth M.; Varughese, Anna M.; Mahmoud, Mohamed; Carey, Patricia M.; Subramanyam, Rajeev; Lerman, Jerrold (2015). “Case report of transfusion-related acute lung injury in a pediatric spine surgery patient transfused leukoreduced red blood cells”. Pediatric Anesthesia. 25 (12): 1294–7. doi:10.1111/pan.12696. PMID 26126598. S2CID 5106831.
• Association Bulletin #14-02. TRALI Risk Mitigation for Plasma and Whole Blood for Allogeneic Transfusion. Bethesda: AABB; 1/29/2014

Pathophysiology

In TRALI, first-hit risk factors include long-term excessive alcohol use, shock, liver surgery, current smoking, higher peak airway pressure while undergoing mechanical ventilation, positive intravascular fluid balance, low levels of interleukin-10, and systemic inflammation. Systemic inflammation may be reflected in the plasma cytokine profiles but also via increased levels of C-reactive protein (CRP), an acute-phase protein that rapidly increases during acute infections and inflammation and is widely used clinically as a biomarker of inflammation. CRP has been shown to be elevated in TRALI patients and, in a mouse model, to functionally enable the first hit in the development of TRALI by increasing the accumulation in the lungs of a neutrophil homologous to interleukin-8. Another factor that can predispose patients to TRALI is pre-existing lung injury, which causes white blood cells to localize in the lungs’ blood vessels. The second hit in TRALI may be conveyed by anti-leukocyte antibodies or other factors present in the transfusion product. In approximately 80% of cases, anti-HLA class I or II or anti-HNA antibodies are implicated as involved in triggering TRALI, although that figure may be even higher depending on the detection methods used. In the remaining 20% of TRALI cases, non–antibody factors or biological response modifiers are suggested to contribute the second hit, and these may possibly include lipid mediators, extracellular vesicles, and aged blood cells.

• Kleinman S, Kor DJ. “Transfusion-related acute lung injury (TRALI).” In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Last updated 5/11/17. Accessed via http://www.uptodate.com/contents/transfusion-related-acute-lung-injury-trali on 6/28/17.
• Semple, John W.; Rebetz, Johan; Kapur, Rick (April 25, 2019). “Transfusion-associated circulatory overload and transfusion-related acute lung injury”. Blood. 133 (17): 1840–1853. doi:10.1182/blood-2018-10-860809. ISSN 1528-0020. PMID 30808638.

Diagnosis

TRALI is defined as an acute lung injury that is temporally related to a blood transfusion; specifically, it occurs within the first six hours following a transfusion.

• Toy P, Popovsky MA, Abraham E, Ambruso DR, Holness LG, Kopko PM, McFarland JG, Nathens AB, Silliman CC, Stroncek D (2005). “Transfusion-related acute lung injury: definition and review”. Critical Care Medicine. 33 (4): 721–6. doi:10.1097/01.ccm.0000159849.94750.51. PMID 15818095.

It is typically associated with plasma components such as platelets and fresh frozen plasma, though cases have been reported with packed red blood cells since there is some residual plasma in the packed cells.

• Association Bulletin #14-02. TRALI Risk Mitigation for Plasma and Whole Blood for Allogeneic Transfusion. Bethesda: AABB; 1/29/2014

Incidents have also been reported with other blood products including “cryoprecipitate, granulocytes, intravenous immune globulin, allogeneic and autologous stem cells”.

• Cho MS, Modi P, Sharma S. Transfusion-related Acute Lung Injury. 2020 Jul 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID 29939623.

• Cryoprecipitate, also called cryo for short, is a frozen blood product prepared from blood plasma. Cross-matching (compatibility testing) is not necessary and all ABO groups are acceptable for transfusion to people of all ABO types.
  • Fung MK, Grossman BJ, Hillyer CD, Westhoff CM (2014). Technical manual (18th ed.). Bethesda, Md.: American Association of Blood Banks. ISBN 978-1563958885. OCLC 881812415.
  • Each unit (around 10 to 15 mL) typically provides:^[5]
    • Fibrinogen 150–250 mg with a half-life of 100–150 hours
    • Factor VIII 80–150 U with a half-life of 12 hours
    • Factor XIII 50–75 U with a half-life of 150–300 hours.
    • von Willebrand factor 100–150 U with a half-life of 24 hours
    • Cryoprecipitate also contains fibronectin; however there are no clear indications for fibronectin replacement.
      •  “CRYO (cryoprecipitate) pharmacology”. Medscape.
  • Adverse effects reported with the usage of cryoprecipitate include hemolytic transfusion reactions, febrile non-hemolytic reactions, allergic reactions (ranging from urticaria to anaphylaxis), septic reactions, transfusion related acute lung injury, circulatory overload, transfusion-associated graft-versus-host disease, and post-transfusion purpura.
    •  “CRYO (cryoprecipitate) Adverse Effects”. Medscape.
• 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, that is, they have varying shapes (morphology) of the nucleus (segmented, irregular; often lobed into three segments); and are referred to as polymorphonuclear leukocytes (PMN, PML, or PMNL). In common terms, polymorphonuclear granulocyte refers specifically to “neutrophil granulocytes”, the most abundant of the granulocytes; the other types (eosinophils, basophils, and mast cells) have varying morphology. Granulocytes are produced via granulopoiesis in the bone marrow.
  • WebMD (2009). “granulocyte”. Webster’s New World Medical Dictionary (3rd ed.). Houghton Mifflin Harcourt. p. 181. ISBN 978-0-544-18897-6.
  • WebMD (2009). “leukocyte, polymorphonuclear”. Webster’s New World Medical Dictionary (3rd ed.). Houghton Mifflin Harcourt. p. 244. ISBN 978-0-544-18897-6.
  • There are four types of granulocytes (full name polymorphonuclear granulocytes). Except for the mast cells, their names are derived from their staining characteristics; for example, the most abundant granulocyte is the neutrophil granulocyte, which has neutrally staining cytoplasmic granules.
    • Basophils
    • Eosinophils
    • Neutrophils
    • Mast cells
      • Breedveld A, Groot Kormelink T, van Egmond M, de Jong EC (October 2017). “Granulocytes as modulators of dendritic cell function”. Journal of Leukocyte Biology. 102 (4): 1003–1016. doi:10.1189/jlb.4MR0217-048RR. PMID 28642280.
  • Examples of toxic materials produced or released by degranulation by granulocytes on the ingestion of microorganisms are:
    • Antimicrobial agents (Defensins and Eosinophil cationic protein)
    • Enzymes
      • Acid hydrolases: further digest bacteria
      • Lysozyme: dissolves cell walls of some gram-positive bacteria
    • Low pH vesicles (3.5-4.0)
    • Toxic nitrogen oxides (nitric oxide)
    • Toxic oxygen-derived products (e.g., superoxide, hydrogen peroxide, hydroxy radicals, singlet oxygen, hypohalite)
  • Granulocytopenia is an abnormally low concentration of granulocytes in the blood. This condition reduces the body’s resistance to many infections. Closely related terms include agranulocytosis (etymologically, “no granulocytes at all”; clinically, granulocyte levels less than 5% of normal) and neutropenia (deficiency of neutrophil granulocytes). Granulocytes live only one to two days in circulation (four days in spleen or other tissue), so transfusion of granulocytes as a therapeutic strategy would confer a very short-lasting benefit. In addition, there are many complications associated with such a procedure.
  • Research suggests giving granulocyte transfusions to prevent infections decreased the number of people who had a bacterial or fungal infection in the blood. Further research suggests participants receiving therapeutic granulocyte transfusions show no difference in clinical reversal of concurrent infection.
    • Estcourt LJ, Stanworth S, Doree C, Blanco P, Hopewell S, Trivella M, Massey E (June 2015). “Granulocyte transfusions for preventing infections in people with neutropenia or neutrophil dysfunction”. The Cochrane Database of Systematic Reviews. 2018 (6): CD005341. doi:10.1002/14651858.cd005341.pub3. PMC 4538863. PMID 26118415.
    • Estcourt LJ, Stanworth SJ, Hopewell S, Doree C, Trivella M, Massey E (April 2016). “Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction”. The Cochrane Database of Systematic Reviews. 4 (7): CD005339. doi:10.1002/14651858.cd005339.pub2. PMC 4930145. PMID 27128488.
  • There is usually a granulocyte chemotactic defect in individuals suffering from type 1 diabetes mellitus.
• Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, Kawasaki disease, certain cases of HIV/AIDS and measles, Guillain-Barré syndrome, and certain other infections when a more specific immunoglobulin is not available. Depending on the formulation it can be given by injection into muscle, a vein, or under the skin. The effects last a few weeks.
  • Common side effects include pain at the site of injection, muscle pain, and allergic reactions. Other severe side effects include kidney problems, anaphylaxis, blood clots, and red blood cell breakdown. Use is not recommended in people with some types of IgA deficiency. Use appears to be relatively safe during pregnancy. Human immunoglobulin is made from human blood plasma. It contains antibodies against many viruses.
    • “Immune Globulin”. The American Society of Health-System Pharmacists. Archived from the original on 9 January 2017. Retrieved 8 January 2017.
    • British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. pp. 867–71. ISBN 9780857111562.
  • Human immunoglobulin therapy first occurred in the 1930s and a formulation for injection into a vein was approved for medical use in the United States in 1981.
    • Etzioni A, Ochs HD (2014). Primary Immunodeficiency Disorders: A Historic and Scientific Perspective. Academic Press. pp. 283–84. ISBN 9780124115545. Archived from the original on 9 January 2017.
  • Although immunoglobulin is frequently used for long periods of time and is generally considered safe, immunoglobulin therapy can have severe adverse effects, both localized and systemic. Subcutaneous administration of immunoglobulin is associated with a lower risk of both systemic and localized risk when compared to intravenous administration (hyaluronidase-assisted subcutaneous administration is associated with a greater frequency of adverse effects than traditional subcutaneous administration but still a lower frequency of adverse effects when compared to intravenous administration).
  • Local side effects of immunoglobulin infusions most frequently include an injection site reaction (reddening of the skin around the injection site), itching, rash, and hives. Less serious systemic side effects to immunoglobulin infusions include an increased heart rate, hyper or hypotension, an increased body temperature, diarrhea, nausea, abdominal pain, vomiting, arthralgia or myalgia, dizziness, headache, fatigue, fever, and pain.
    •  “Immune Globulin”. Dynamed. Archived from the original on 8 December 2015. Retrieved 23 November 2015.(Subscription may be required or content may be available in libraries.)
  • Serious side effects of immunoglobulin infusions include chest discomfort or pain, myocardial infarction, tachycardia, hyponatremia, hemolysis, hemolytic anemia, thrombosis, hepatitis, anaphylaxis, backache, aseptic meningitis, acute kidney injury, hypokalemic nephropathy, pulmonary embolism, and transfusion related acute lung injury. There is also a small chance that even given the precautions taken in preparing immunoglobulin preparations, an immunoglobulin infusion may pass a virus to its recipient. Some immunoglobulin solutions also contain isohemagglutinins, which in rare circumstances can cause hemolysis by the isohemagglutinins triggering phagocytosis.
    •  “Immune Globulin”. Dynamed. Archived from the original on 8 December 2015. Retrieved 23 November 2015.(Subscription may be required or content may be available in libraries.)
    • Daw Z, Padmore R, Neurath D, Cober N, Tokessy M, Desjardins D, et al. (August 2008). “Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis”. Transfusion. 48 (8): 1598–1601. doi:10.1111/j.1537-2995.2008.01721.x. PMID 18466176. S2CID 6010463.
  • Immunoglobulin therapy also interferes with the ability of the body to produce a normal immune response to an attenuated live virus vaccine for up to a year, can result in falsely elevated blood glucose levels, and can interfere with many of the IgG-based assays often used to diagnose a patient with a particular infection.
    • “Immune Globulin”. Dynamed. Archived from the original on 8 December 2015. Retrieved 23 November 2015.(Subscription may be required or content may be available in libraries.)
    • Lichtiger B (April 1994). “Laboratory Serologic Problems Associated with Administration of Intravenous IgG”. Current Issues in Transfusion Medicine. The University of Texas M. D. Anderson Cancer Center. 3: 1–7. Archived from the original on 5 March 2016. Retrieved 23 November 2015.
  • Routes of administration
    • 1950s – intramuscular
    • 1980s – intravenous
    • 1990s – subcutaneous
  • Hyperimmune globulins are a class of immunoglobulins prepared in a similar way as for normal human immunoglobulin, except that the donor has high titers of antibody against a specific organism or antigen in their plasma. Some agents against which hyperimmune globulins are available include hepatitis B, rabies, tetanus toxin, varicella-zoster, etc. Administration of hyperimmune globulin provides “passive” immunity to the patient against an agent. This is in contrast to vaccines that provide “active” immunity. However, vaccines take much longer to achieve that purpose while hyperimmune globulin provides instant “passive” short-lived immunity. Hyperimmune globulin may have serious side effects, thus usage is taken very seriously.^{[citation needed]} Hyperimmune serum and plasma contain high amounts of an antibody, as a consequence of disease convalescence or of repeated immunization. Hyperimmune plasma is used in veterinary medicine, and hyperimmune plasma derivatives are used to treat snakebite. It has been hypothesized that hyperimmune serum may be an effective therapy for persons infected with the Ebola virus.
    • Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, et al. (January 2015). “The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis”. The Journal of Infectious Diseases. 211 (1): 80–90. doi:10.1093/infdis/jiu396. PMC 4264590. PMID 25030060.
    • “Antivenoms”. www.who.int. Retrieved 23 May 2023.
    • “What is Hyperimmunized Plasma?”. Plasvacc USA. 20 May 2021. Retrieved 23 May 2023.
    • Dias da Silva W, De Andrade SA, Megale ÂA, De Souza DA, Sant’Anna OA, Magnoli FC, et al. (September 2022). “Antibodies as Snakebite Antivenoms: Past and Future”. Toxins. 14 (9): 606. doi:10.3390/toxins14090606. PMC 9503307. PMID 36136544.
    • Kudoyarova-Zubavichene NM, Sergeyev NN, Chepurnov AA, Netesov SV (February 1999). “Preparation and use of hyperimmune serum for prophylaxis and therapy of Ebola virus infections”. The Journal of Infectious Diseases. 179 (Suppl 1): S218–S223. doi:10.1086/514294. PMID 9988187.
• Allotransplant (allo- meaning “other” in Greek) is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, or homograft. Most human tissue and organ transplants are allografts.
  • Allografts can be referred to as “homostatic” if they are biologically inert when transplanted, such as bone and cartilage.
    • (W. P. Longmire, J. National Cancer Institute 14, 669: The term homostatic graft might be applied to inert tissues such as bone and cartilage when transferred from one individual to another of the same species; and the term homovital graft might be used in reference to grafts whose cells must continue to grow and reproduce for the graft to be effective after similar transplantation; H. Conway, The Bulletin of the Hong Kong Chinese Medical Association 13, 43: These grafts persist however as homostatic grafts and are completely replaced by host tissues in time.)
  • An immune response against an allograft or xenograft is termed rejection. An allogenic bone marrow transplant can result in an immune attack on the recipient, called graft-versus-host disease.
  • Material is obtained from a donor who is a living person, or a deceased person’s body receiving mechanical support or ventilation, or a deceased person’s body whose heart stopped beating.
  • As with many operations, allotransplantation risks some side effects. A limiting factor in tissue allotransplantation for reconstructive surgery deals with the side effects of immunosuppression (metabolic disorders, malignancies, opportunistic infections) which is a predominant issue. The risk of transmitting infection is high.
    • Petit, F.; Minns, A. B.; Dubernard, J. M.; Hettiaratchy, S.; Lee, W. P. (2003). “Composite Tissue Allotransplantation and Reconstructive Surgery”. Annals of Surgery. 237 (1): 19–25. doi:10.1097/00000658-200301000-00004. PMC 1513974. PMID 12496526.
• Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person (auto- meaning “self” in Greek).
  • A common example is the removal of a piece of bone (usually from the hip) and its being ground into a paste for the reconstruction of another portion of bone.
  • Autotransplantation, although most common with blood, bone, or skin, can be used for a wide variety of organs. One of the rare examples is autotransplantation of a kidney from one side of the body to the other. Kidney autotransplantation is used as a treatment for nutcracker syndrome.
    • Boodman, Sandra D. (October 24, 2020). “Stomach pain was ruining her life. Then a scan provided a life-changing clue”. Washington Post.
  • Blood donation prior to colorectal cancer surgery seemed causative for a worse overall and colorectal cancer specific survival.
    • Harlaar, JJ; Gosselink, MP; Hop, WC; Lange, JF; Busch, OR; Jeekel, H (November 2012). “Blood transfusions and prognosis in colorectal cancer: long-term results of a randomized controlled trial”. Annals of Surgery. 256 (5): 681–7. doi:10.1097/SLA.0b013e318271cedf. PMID 23095610. S2CID 35798344.
• Xenotransplantation (xenos- from the Greek meaning “foreign” or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another.
  • Xenotransplantation. Definition by the World Health Organization
    • enotransplantation is an artificial method of creating an animal-human chimera, that is, a human with a subset of animal cells. In contrast, an individual where each cell contains genetic material from a human and an animal is called a human–animal hybrid.
      • Sarah Taddeo, Jason S. Robert (2014-11-04). “”Hybrids and Chimeras: A Consultation on the Ethical and Social Implications of Creating Human/Animal Embryos in Research” (2007), by the HFEA”. The Embryo Project at Arizona State University.
    • It is common for patients and physicians to use the term “allograft” imprecisely to refer to either allograft (human-to-human) or xenograft (animal-to-human), but it is helpful scientifically (for those searching or reading the scientific literature) to maintain the more precise distinction in usage.^{[citation needed]}
    • To date,^{[citation needed]} no xenotransplantation trials have been entirely successful due to the many obstacles arising from the response of the recipient’s immune system. Xenozoonoses are one of the biggest threats to rejections, as they are xenogenetic infections. The introduction of these microorganisms are a big issue that lead to the fatal infections and then rejection of the organs. This response, which is generally more extreme than in allotransplantations, ultimately results in rejection of the xenograft, and can in some cases result in the immediate death of the recipient. There are several types of rejection organ xenografts are faced with, these include hyperacute rejection, acute vascular rejection, cellular rejection, and chronic rejection.^{[citation needed]}
      • Boneva, RS; Folks, TM; Chapman, LE (January 2001). “Infectious disease issues in xenotransplantation”. Clinical Microbiology Reviews. 14 (1): 1–14. doi:10.1128/CMR.14.1.1-14.2001. PMC 88959. PMID 11148000.
    • A rapid, violent, and hyperacute response comes as a result of antibodies present in the host organism. These antibodies are known as xenoreactive natural antibodies (XNAs).
      • Dooldeniya, M D; Warrens, AN (2003). “Xenotransplantation: where are we today?”. Journal of the Royal Society of Medicine. 96 (3): 111–117. doi:10.1177/014107680309600303. PMC 539416. PMID 12612110.
    • This rapid and violent type of rejection occurs within minutes to hours from the time of the transplant. It is mediated by the binding of XNAs (xenoreactive natural antibodies) to the donor endothelium, causing activation of the human complement system, which results in endothelial damage, inflammation, thrombosis and necrosis of the transplant. XNAs are first produced and begin circulating in the blood in neonates, after colonization of the bowel by bacteria with galactose moieties on their cell walls. Most of these antibodies are the IgM class, but also include IgG, and IgA.
      • Taylor, L. (2007) Xenotransplantation. Emedicine.com
    • The epitope XNAs target is an α-linked galactose moiety, galactose-alpha-1,3-galactose (also called the α-Gal epitope), produced by the enzyme alpha-galactosyltransferase. Most non-primates contain this enzyme thus, this epitope is present on the organ epithelium and is perceived as a foreign antigen by primates, which lack the galactosyl transferase enzyme. In pig to primate xenotransplantation, XNAs recognize porcine glycoproteins of the integrin family.
      • Taylor, L. (2007) Xenotransplantation. Emedicine.com
      • Candinas, D.; Adams, D. H. (2000). “Xenotransplantation: Postponed by a millennium?”. QJM. 93 (2): 63–66. doi:10.1093/qjmed/93.2.63. PMID 10700475.
    • The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a cascade of events leading to: destruction of endothelial cells, platelet degranulation, inflammation, coagulation, fibrin deposition, and hemorrhage. The result is thrombosis and necrosis of the xenograft.
      • Taylor, L. (2007) Xenotransplantation. Emedicine.com
• Synthetic and metal implants. Unlike allografts, such grafts do not corporate into the body.

Transfusion-related acute lung injury is a diagnosis upon examination of clinical manifestations that appear within 6 hours of transfusion, such as acute respiratory distress, tachypnea, hypotension, cyanosis, and dyspnea. TRALI is an uncommon syndrome, that is due to the presence of leukocyte antibodies in transfused plasma. It is believed to occur in approximately one in every 5000 transfusions.

• Silliman, C. C.; Fung, Y. L.; Ball, J. B.; Khan, S. Y. (2009). “Transfusion-related acute lung injury (TRALI): Current Concepts and Misconceptions”. Blood Reviews. 23 (6): 245–255. doi:10.1016/j.blre.2009.07.005. PMC 3134874. PMID 19699017.

Leukoagglutination and pooling of granulocytes in the recipient’s lungs may occur, with release of the contents of leukocyte granules, and resulting injury to cellular membranes, endothelial surfaces, and potentially to lung parenchyma. In most cases leukoagglutination results in mild dyspnea and pulmonary infiltrates within about 6 hours of transfusion, and spontaneously resolves.^{[citation needed]}

Occasionally more severe lung injury occurs as a result of this phenomenon and acute respiratory distress syndrome (ARDS) results. Leukocyte filters may prevent TRALI for those patients whose lung injury is due to leukoagglutination of the donor white blood cells, but because most TRALI is due to donor antibodies to leukocytes, filters are not helpful in TRALI prevention. Transfused plasma (from any component source) may also contain antibodies that cross-react with platelets in the recipient, producing usually mild forms of posttransfusion purpura or platelet aggregation after transfusion.^{[citation needed]}

Another nonspecific form of immunologic transfusion complication is mild to moderate immunosuppression consequent to transfusion. This effect of transfusion is not completely understood, but appears to be more common with cellular transfusion and may result in both desirable and undesirable effects. Mild immunosuppression may benefit organ transplant recipients and patients with autoimmune diseases; however, neonates and other already immunosuppressed hosts may be more vulnerable to infection, and cancer patients may possibly have worse outcomes postoperatively.^{[citation needed]}

Treatment

The mainstay of therapy in TRALI is supportive care. Oxygen supplementation is employed in all reported cases of TRALI, and 72% of patients require aggressive respiratory support. To support blood pressure, intravenous administration of fluids, as well as vasopressors, are essential. In treating TRALI, diuretics are to be avoided, although they are indicated in the management of transfusion associated circulatory overload. Corticosteroids can be beneficial.^{[citation needed]}

Epidemiology

The true incidence of TRALI is unknown because of the difficulty in making the diagnosis and because of underreporting. It is estimated to occur in 1:1300 to 1:5000 transfusions of plasma-containing products. TRALI is the leading reported cause of death related to transfusion in the United States; more than 20 cases were reported per year from 2003 to 2005.^{[citation needed]} The immune mediated form of TRALI occurs approximately once every 5000 transfusions and has a mortality of 6–9%.

• Bux, J. (2005). “Transfusion-related acute lung injury (TRALI): a serious adverse event of blood transfusion”. Vox Sanguinis. 89 (1): 1–10. doi:10.1111/j.1423-0410.2005.00648.x. PMID 15938734. S2CID 26023653.

See also

• Flash pulmonary edema

Flash pulmonary edema (FPE) is the name given to a clinical syndrome of acute heart failure that begins suddenly and accelerates rapidly. Frequently the most noticeable abnormality is edema of the lungs. Nevertheless it is a cardiovascular disease not a pulmonary disease. It is also known by other appellations including sympathetic crashing pulmonary edema. It is often associated with severe hypertension but may be precipitated by acute myocardial infarction or mitral regurgitation, but can be also caused by aortic regurgitation, heart failure, or almost any cause leading to elevated left ventricular filling pressures. Treatment of FPE should be directed at the underlying cause, but the mainstays are nitroglycerin, ensuring adequate oxygenation with non-invasive ventilation, and decrease of pulmonary circulation pressures while FPE stays. Recurrence of FPE is thought to be associated with hypertension and may signify renal artery stenosis. Prevention of recurrence is based on managing or preventing hypertension, coronary artery disease, renovascular hypertension, and heart failure.

• Siddiqua, Naazia; Mathew, Roshan; Sahu, Ankit Kumar; Jamshed, Nayer; Bhaskararayuni, Jyothiswaroop; Aggarwal, Praveen; Kumar, Akshay; Khan, Maroof Ahmad (2023-11-28). “High-dose versus low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised controlled trial”. Emergency Medicine Journal: emermed–2023–213285. doi:10.1136/emermed-2023-213285. ISSN 1472-0205.
• Gandhi, Sanjay K.; Powers, John C.; Nomeir, Abdel-Mohsen; Fowle, Karen; Kitzman, Dalane W.; Rankin, Kevin M.; Little, William C. (2001-01-04). “The Pathogenesis of Acute Pulmonary Edema Associated with Hypertension”. New England Journal of Medicine. 344 (1): 17–22. doi:10.1056/NEJM200101043440103. ISSN 0028-4793.
• Long, Brit; Koyfman, Alex; Gottlieb, Michael (2018). “Management of Heart Failure in the Emergency Department Setting: An Evidence-Based Review of the Literature”. The Journal of Emergency Medicine. 55 (5): 635–646. doi:10.1016/j.jemermed.2018.08.002. PMID 30266198. S2CID 52884356.
• Kramer K, Kirkman P, Kitzman D, Little WC (Sep 2000). “Flash pulmonary edema: association with hypertension and recurrence despite coronary revascularization”. Am Heart J. 140 (3): 451–5. doi:10.1067/mhj.2000.108828. PMID 10966547.
• Pickering TG, Herman L, Devereux RB, Sotelo JE, James GD, Sos TA, Silane MF, Laragh JH (1988). “Recurrent pulmonary oedema in hypertension due to bilateral renal artery stenosis: treatment by angioplasty or surgical revascularisation”. Lancet. 332 (8610): 551–2. doi:10.1016/S0140-6736(88)92668-2. PMID 2900930. S2CID 36141498.

Main Article References

1. Gajic, Ognjen; Moore, S. Breanndan (2005). “Transfusion-Related Acute Lung Injury”. Mayo Clinic Proceedings. 80 (6): 766–770. doi:10.1016/S0025-6196(11)61531-0. PMID 15945528.
2. U.S. Food and Drug Administration, Center for Biologics Evaluation and Research. Fatalities Reported to FDA Following Blood Collection and Transfusion: Annual Summary for Fiscal Year 2012. Bethesda, Md: U.S. Food and Drug Administration.
3. Silliman, C. C.; Fung, Y. L.; Ball, J. B.; Khan, S. Y. (2009). “Transfusion-related acute lung injury (TRALI): Current Concepts and Misconceptions”. Blood Reviews. 23 (6): 245–255. doi:10.1016/j.blre.2009.07.005. PMC 3134874. PMID 19699017.
4. Cho MS, Modi P, Sharma S. Transfusion-related Acute Lung Injury. 2020 Jul 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID 29939623
5. “Transfusion-related acute lung injury (TRALI)”. Professional Education.
6. Muller, J.Y. (2005). “Le TRALI : du diagnostic à la prévention” [TRALI: from diagnosis to prevention]. Transfusion Clinique et Biologique (in French). 12 (2): 95–102. doi:10.1016/j.tracli.2005.04.007. PMID 15894508. INIST 16924693.
7. Cleary, Simon J.; Kwaan, Nicholas; Tian, Jennifer J.; Calabrese, Daniel R.; Mallavia, Beñat; Magnen, Mélia; Greenland, John R.; Urisman, Anatoly; Singer, Jonathan P.; Hays, Steven R.; Kukreja, Jasleen; Hay, Ariel M.; Howie, Heather L.; Toy, Pearl; Lowell, Clifford A.; Morrell, Craig N.; Zimring, James C.; Looney, Mark R. (5 October 2020). “Complement activation on endothelium initiates antibody-mediated acute lung injury”. Journal of Clinical Investigation. 130 (11): 5909–5923. doi:10.1172/JCI138136. PMC 7598054. PMID 32730229.
8. Dykes, A.; Smallwood, D.; Kotsimbos, T.; Street, A. (June 2000). “Transfusion-Related Acute Lung Injury (Trali) In A Patient With A Single Lung Transplant: Correspondence”. British Journal of Haematology. 109 (3): 674–676. doi:10.1046/j.1365-2141.2000.01999.x. PMID 10886228. S2CID 42922617.
9. Silliman, Christopher C. (2006). “The two-event model of transfusion-related acute lung injury”. Critical Care Medicine. 34 (5 Suppl): S124–131. doi:10.1097/01.CCM.0000214292.62276.8E. ISSN 0090-3493. PMID 16617256. S2CID 36068011.
10. Harmening, Denise (2019). Modern Blood Banking & Transfusion Practices. Philadelphia: F.A. Davis Company. p. 381. ISBN 9780803668881.
11. Cudilo, Elizabeth M.; Varughese, Anna M.; Mahmoud, Mohamed; Carey, Patricia M.; Subramanyam, Rajeev; Lerman, Jerrold (2015). “Case report of transfusion-related acute lung injury in a pediatric spine surgery patient transfused leukoreduced red blood cells”. Pediatric Anesthesia. 25 (12): 1294–7. doi:10.1111/pan.12696. PMID 26126598. S2CID 5106831.
12. Association Bulletin #14-02. TRALI Risk Mitigation for Plasma and Whole Blood for Allogeneic Transfusion. Bethesda: AABB; 1/29/2014
13. Kleinman S, Kor DJ. “Transfusion-related acute lung injury (TRALI).” In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Last updated 5/11/17. Accessed via http://www.uptodate.com/contents/transfusion-related-acute-lung-injury-trali on 6/28/17.
14. Semple, John W.; Rebetz, Johan; Kapur, Rick (April 25, 2019). “Transfusion-associated circulatory overload and transfusion-related acute lung injury”. Blood. 133 (17): 1840–1853. doi:10.1182/blood-2018-10-860809. ISSN 1528-0020. PMID 30808638.
15. Toy P, Popovsky MA, Abraham E, Ambruso DR, Holness LG, Kopko PM, McFarland JG, Nathens AB, Silliman CC, Stroncek D (2005). “Transfusion-related acute lung injury: definition and review”. Critical Care Medicine. 33 (4): 721–6. doi:10.1097/01.ccm.0000159849.94750.51. PMID 15818095.
16. Cho MS, Modi P, Sharma S. Transfusion-related Acute Lung Injury. 2020 Jul 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID 29939623.
17. Bux, J. (2005). “Transfusion-related acute lung injury (TRALI): a serious adverse event of blood transfusion”. Vox Sanguinis. 89 (1): 1–10. doi:10.1111/j.1423-0410.2005.00648.x. PMID 15938734. S2CID 26023653.

External links

• Transfusion Related Acute Lung Injury – US Food and Drug Administration (FDA).
• Neutrophil Antigens and Antibodies – American Society of Histocompatibility and Immunogenetics.

Blood transfusion and transfusion medicine

Categories: 

• Complications of surgical and medical care
• Intensive care medicine
• Lung disorders
• Transfusion reactions
• Transfusion medicine