Transfusion-related acute lung injury

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Transfusion-related acute lung injury
Other namesTRALI
Hyaline membranes - very high mag.jpg
Micrograph of diffuse alveolar damage, the histologic correlate of TRALI; H&E stain
Specialty Pulmonology

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. [1] 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. [2]

Contents

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. [3]

Delayed TRALI occurs 6 to 72 hours after transfusion completion. It is associated with a higher rate of mortality. [4]

Cause

The cause of TRALI is currently not fully understood. 80–85% of cases are thought to be immune mediated. [5] [6] 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. [7] [8] 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. [6] 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 [9] 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. [10]

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. [3]

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. [11] 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. [12] To mitigate the risk of TRALI, female donors are excluded from fresh frozen plasma donation in Germany as of 2009 if they have a history of pregnancy and there are no HLA/HNA screening results available, which has resulted in a significant reduction of TRALI reports. [13]

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. [14] 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. [15]

Diagnosis

Chest X-ray of transfusion-related acute lung injury (TRALI) compared to chest X-ray of the same person after treatment Transfusion-related acute lung injury chest X-ray.gif
Chest X-ray of transfusion-related acute lung injury (TRALI) compared to chest X-ray of the same person after treatment

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. [16]

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. [12] Incidents have also been reported with other blood products including "cryoprecipitate, granulocytes, intravenous immune globulin, allogeneic and autologous stem cells". [17]

It 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. [3] 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%. [18]

See also

Related Research Articles

<span class="mw-page-title-main">Blood type</span> Classification of blood based on antibodies and antigens on red blood cell surfaces

A blood type is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system. Some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens can stem from one allele and collectively form a blood group system.

<span class="mw-page-title-main">Inflammation</span> Physical effects resulting from activation of the immune system

Inflammation is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function.

<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, plasma, platelets, and other clotting factors. White blood cells are transfused only in very rare circumstances, since granulocyte transfusion has limited applications. Whole blood has come back into use in the setting of trauma.

<span class="mw-page-title-main">Platelet</span> Component of blood aiding in coagulation

Platelets or thrombocytes are a blood component whose function is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm derived from the megakaryocytes of the bone marrow or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates, thrombocytes circulate as intact mononuclear cells.

<span class="mw-page-title-main">Blood plasma</span> Liquid component of blood

Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but which contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intravascular part of extracellular fluid. It is mostly water, and contains important dissolved proteins, glucose, clotting factors, electrolytes, hormones, carbon dioxide, and oxygen. It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood-related disorders.

<span class="mw-page-title-main">Neutrophil</span> Type of white blood cell

Neutrophils are a type of white blood cell. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in different animals.

<span class="mw-page-title-main">Pulmonary edema</span> Fluid accumulation in the tissue and air spaces of the lungs

Pulmonary edema, also known as pulmonary congestion, is excessive fluid accumulation in the tissue or air spaces of the lungs. This leads to impaired gas exchange, most often leading to shortness of breath (dyspnea) which can progress to hypoxemia and respiratory failure. Pulmonary edema has multiple causes and is traditionally classified as cardiogenic or noncardiogenic.

<span class="mw-page-title-main">Transplant rejection</span> Rejection of transplanted tissue by the recipients immune system

Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant.

<span class="mw-page-title-main">Graft-versus-host disease</span> Medical condition

Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.

<span class="mw-page-title-main">Plateletpheresis</span> Method of collecting platelets from blood

Plateletpheresis is the process of collecting thrombocytes, more commonly called platelets, a component of blood involved in blood clotting. The term specifically refers to the method of collecting the platelets, which is performed by a device used in blood donation that separates the platelets and returns other portions of the blood to the donor. Platelet transfusion can be a life-saving procedure in preventing or treating serious complications from bleeding and hemorrhage in patients who have disorders manifesting as thrombocytopenia or platelet dysfunction. This process may also be used therapeutically to treat disorders resulting in extraordinarily high platelet counts such as essential thrombocytosis.

Intraoperative blood salvage (IOS), also known as cell salvage, is a specific type of autologous blood transfusion. Specifically IOS is a medical procedure involving recovering blood lost during surgery and re-infusing it into the patient. It is a major form of autotransfusion.

Hemolytic disease of the newborn (anti-Rhc) can range from a mild to a severe disease. It is the third most common cause of severe HDN. Rh disease is the most common and hemolytic disease of the newborn (anti-Kell) is the second most common cause of severe HDN. It occurs more commonly in women who are Rh D negative.

Hemolytic disease of the newborn (anti-RhE) is caused by the anti-RhE antibody of the Rh blood group system. The anti-RhE antibody can be naturally occurring, or arise following immune sensitization after a blood transfusion or pregnancy.

A panel-reactive antibody (PRA) is a group of antibodies in a test serum that are reactive against any of several known specific antigens in a panel of test leukocytes or purified HLA antigens from cells. It is an immunologic metric routinely performed by clinical laboratories on the blood of people awaiting organ transplantation.

<span class="mw-page-title-main">Diffuse panbronchiolitis</span> Inflammatory lung disease

Diffuse panbronchiolitis (DPB) is an inflammatory lung disease of unknown cause. It is a severe, progressive form of bronchiolitis, an inflammatory condition of the bronchioles. The term diffuse signifies that lesions appear throughout both lungs, while panbronchiolitis refers to inflammation found in all layers of the respiratory bronchioles. DPB causes severe inflammation and nodule-like lesions of terminal bronchioles, chronic sinusitis, and intense coughing with large amounts of sputum production.

Febrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reaction. It is a benign occurrence with symptoms that include fever but not directly related with hemolysis. It is caused by cytokine release from leukocytes within the donor product as a consequence of white blood cell breakdown .These inflammatory mediators accumulate during the storage of the donated blood, and so the frequency of this reaction increases with the storage length of donated blood. This is in contrast to transfusion-associated acute lung injury, in which the donor plasma has antibodies directed against the recipient HLA antigens, mediating the characteristic lung damage.

An acute hemolytic transfusion reaction (AHTR), also called immediate hemolytic transfusion reaction, is a life-threatening reaction to receiving a blood transfusion. AHTRs occur within 24 hours of the transfusion and can be triggered by a few milliliters of blood. The reaction is triggered by host antibodies destroying donor red blood cells. AHTR typically occurs when there is an ABO blood group incompatibility, and is most severe when type A donor blood is given to a type O recipient.

Plasma frozen within 24 hours after phlebotomy, commonly called FP24, PF‑24, or similar names, is a frozen human blood plasma product used in transfusion medicine. It differs from fresh-frozen plasma (FFP) in that it is frozen within 24 hours of blood collection, whereas FFP is frozen within 8 hours. The phrase "FFP" is sometimes used to refer to any frozen blood plasma product intended for transfusion.

Serious Hazards of Transfusion (SHOT) is the United Kingdom's haemovigilance scheme.

A granulocyte transfusion is a medical procedure in which granulocytes are infused into a person's blood. Granulocyte transfusions were historically used to prevent and treat infections in people with neutropenia, 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.

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. 1 2 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. 1 2 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. 1 2 Association Bulletin #14-02. TRALI Risk Mitigation for Plasma and Whole Blood for Allogeneic Transfusion. Bethesda: AABB; 1/29/2014
  13. ↑ Berg, P; Heiden, M; Müller, S; Meyer, B; Witzenhausen, C; Ruppert‐Seipp, G; Kehr, S; Funk, MB (2024-06-18). "A national surveillance system for continuous monitoring of blood transfusion safety: German haemovigilance data". Vox Sanguinis. doi:10.1111/vox.13694.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
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