*Address all correspondence to: [emailprotected]. Finally, the risk factors for post-transplant AIHA should be better addressed and prospective studies on therapeutic options for this treatment-resistant complication are warranted. Only in rare cases, platelet components have to be washed. Downstream hazards range from hemolytic disease of the newborn, to delays and difficulties sourcing antigen-negative blood (when the antibody is known), or an anamnestic response with higher odds of hemolysis on antigen re-exposure (when the antibody becomes unknown by evanescence and healthcare fragmentation). Complement activation appears to be the most important determining factor in these cases. %%EOF In general, intravascular haemolysis is called as an early acute haemolytic transfusion reaction. Data on the incidence of haemolytic transfusion reactions vary from country to country and change over time. They are usually IgM molecules, are rarely active at 37C and usually do not bind complement. IVIG formulations with low isohemagglutinin titers and/or adjustment of dosage can prevent IVIG-induced HA, especially for patients with blood group A. TMA describes a syndrome characterized by microangiopathic HA, thrombocytopenia due to platelet consumption, and microvascular thrombosis (Table 4).25 The formation of platelet-rich thrombi induces mechanical RBC damage and thus intravascular hemolysis. /N 3 Additionally, transplantation-associated thrombotic microangiopathy (TA-TMA) may occur and is associated with significant morbidity and mortality. {{{;}#tp8_\. As a consequence of antibody-dependent cell-mediated cytotoxicity (ADCC) haemoglobinemia and haemoglobinuria may occur similarly to intravascular haemolysis, although the antibodies that caused it do not bind complement components. In the presence of schistocytes and thus the suspicion of microangiopathy, measurement of ADAMTS13 should be considered. It allows to identify malfunctioning procedures leading to transfusion reactions. The macrophage cytotoxins are another mechanism that plays a role in the destruction of red blood cells. Contact our London head office or media team here. Some symptoms of hemolytic anemia are the same as those for other forms of anemia. An acute hemolytic reaction occurs during or shortly after the transfusion (we give some products pretty quickly depending on the case). How long does it take for a hemolytic transfusion to occur? DAT should be performed, although it can be negative in case of rapid clearance of isohemagglutinin-loaded recipient RBCs. endstream endobj 39 0 obj<> endobj 41 0 obj<> endobj 42 0 obj<>/Font<>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 43 0 obj<> endobj 44 0 obj<> endobj 45 0 obj[/ICCBased 50 0 R] endobj 46 0 obj<> endobj 47 0 obj<> endobj 48 0 obj<> endobj 49 0 obj<>stream It is a benign occurrence with symptoms that include fever but The type of laboratory tests performed for early transfusion haemolytic reactions is shown in Table 7. Alloantibodies responsible for haemolysis, needle diameter too small, haematocrit of transfused red blood cells too high, an inappropriate method of freezing/thawing red blood cells, mechanical damage to blood cells, artificial valves, Drug-induced haemolysis of red blood cells. See Table 3. 0000000576 00000 n Hemoglobin monitoring (sometimes repetitively in 1 day in case of severe hemolysis), a full blood count including reticulocytes, blood smear (schistocytes? If blood transfusions are indicated, crossmatching can be unable to identify compatible RBC units, as the autoantibodies are directed against highly prevalent antigens. Hypotension occurs in about 1in 10 cases of intravascular haemolytic transfusion reaction, but is also sometimes observed in extravascular haemolysis. 0000002721 00000 n Although pretransfusion prophylactic paracetamol and diphenhydramine are often routinely administered, there is little evidence to support this practice. WebHemolytic disease of the newborn (also known as HDN or erythroblastosis fetalis) Rh D hemolytic disease of the newborn (also known as Rh disease) ABO hemolytic disease of the newborn (the direct Coombs test may only be weakly positive) Anti-Kell hemolytic disease of the newborn Rh c hemolytic disease of the newborn It is known that a significant proportion of NO does not immediately bind to HbFe2+heme, instead it binds to cysteine, resulting in the formation of the S-nitrosothiol derivative Hb (SNO-Hb). Tests on the ABO system titre in group O apheresis concentrates of platelets show that 26% of samples have an anti-A or anti-A, B antibody titre of 64 or higher. In contrast to ABO incompatibility, donors and recipients lack naturally formed antibodies for non-ABO RBC antigens, occurring only after immunization. Antibodies destroying transfused blood cells are called clinically relevant antibodies that are active invitro at 37C. The recipients body immediately begins to destroy the donated red blood cells resulting in fever, pain, and sometimes severe complications such as kidney failure. A delayed hemolytic transfusion reaction occurs when the recipient develops antibodies to red blood cell antigens between 24 hours and 28 days after a transfusion. Table 1 shows the number of antigenic determinants on the cell surface for selected red blood cell antigens. EdwardB. Flink; The Distinction of Hemolytic and Nonhemolytic Transfusion Reactions. Acute transfusion reactions range from bothersome yet clinically benign to life-threatening reactions. Other antibodies cause intravascular haemolysis, but sometimes they may be accompanied by intravascular haemolysis. NO can bind to thiol groups and haemoglobin haeme [35]. However, the complement system does not work specifically. Other anti-RBC antibody mediated TRs included acute hemolytic transfusion reactions (AHTR) (both host-derived and passively-acquired [from products such as intravenous immunoglobulin]), and delayed hemolytic transfusion reactions (DHTR) occurring with or without serologic findings. Sickle cell disease (NORD) Hereditary spherocytosis. Intravascular haemolysis modulates blood pressure and local blood flow through changes in the metabolism of the physiological vasodilatornitric oxide (NO). However, in those with non-hemolytic ??accessibility.screen-reader.external-link_en_US?? Anti-A, anti-B and anti-AB antibodies are involved in causing an early intravascular transfusion reaction, and transfusion of incompatible blood in the ABO system poses a threat to the recipients life, especially when group A red blood cells are transfused to a patient with group O.Sixty-one (61%) of all haemolytic transfusion-related fatal reactions are associated with the ABO incompatibility [38, 39]. Publishing on IntechOpen allows authors to earn citations and find new collaborators, meaning more people see your work not only from your own field of study, but from other related fields too. Rarely, more severe reactions can Thus, clinical relevant and serious acute hemolytic reactions immediately after graft infusion are rare. It was found that when red blood cells became the bystander of leukocyte reactions and antibodies directed to them, they underwent haemolysis. However, it should be remembered that these difficulties must not cause risk of haemorrhage. On the one hand, these processes lead to the production of a large amount of thrombin that converts fibrinogen to fibrin. In comparison extravascular haemolysis is called delayed haemolytic transfusion reaction and usually occurs 24h or days after the end of the transfusion. Disturbances deemed unrelated to transfusion were excluded. Minor ABO-incompatible HSCT is characterized by the transfer of donor isohemagglutinins directed against the recipient's RBC antigens. For any urgent enquiries please contact our customer services team who are ready to help with any problems. The evaluation of haptoglobin and free hemoglobin in serum and urine can be helpful. Another method of treating early haemolytic transfusion reaction is to use a high dose of 0.4/kg intravenous immunoglobulin per 24h after blood transfusion. Impaired renal function is observed in both intravascular and extravascular haemolytic transfusion reactions, although definitely more frequently in the case of intravascular. It was estimated that the frequency of reactions resulting from the ABO incompatibility was 1:27,318, acute haemolytic transfusion reactions 1:14,901 and delayed haemolytic transfusion reactions 1:9313 per unit of transfused red blood cell concentrate [5]. Often the way out of this situation is transfusion of O RhD negative red blood cells. It enforces the introduction of procedures eliminating further errors. Latter is also supported by growing data on the use of eculizumab in TA-TMA.28-33, A high index of suspicion is required for the diagnosis of TA-TMA. These diseases may relapse and thus HA can be a possible clinical manifestation either of relapse or of graft failure. Reactions range from self-limited febrile reactions to life-threatening intravascular hemolysis. FNHTR manifests as fever and/or chills without Additionally, IgM isohemagglutinins are removed more efficiently than IgG isohemagglutinins, because IgG distributes in both the intravascular and extravascular spaces.14 Furthermore, no consensus on target titer values is available. Finally, current therapeutic approaches for both TA-TMA and post-HSCT autoimmune HA, which are associated with high morbidity and mortality, are discussed. Depending on the severity of the anaemia, transfusion of blood components should be avoided until the antibodies responsible for the reaction have been identified and the appropriate selection of blood cells has been made. We are a community of more than 103,000 authors and editors from 3,291 institutions spanning 160 countries, including Nobel Prize winners and some of the worlds most-cited researchers. WebTransfusion Reactions Allergic Hemolytic (Acute; Delayed) Bacterial Febrile non-hemolytic TRALI Volume Overload Transfusion Reactions: Signs & Symptoms Fever Hypotension Chest Tightness/Dyspnea Nausea/Vomiting etc Immuno-Hemolytic Transfusion Reactions Intravascular vs Extravascular Immediate vs Delayed RE: Is Whole Blood Poised for a Return in Civilian Trauma? Laboratory tests that help to differentiate haemolysis include determination of free haemoglobin in the blood and urine, haptoglobin and lactate dehydrogenase (LDH) and bilirubin. All rights reserved. Our team is growing all the time, so were always on the lookout for smart people who want to help us reshape the world of scientific publishing. In contrast, prospective studies also contain errors due to reaction symptoms often remaining unrecognised or masked by associated diseases, for example, bleeding or liver disease [1]. Copyright 2023 by American Society of Hematology, Prevention and management of HA due to blood group incompatibility, Thrombotic microangiopathic HA after HSCT, Other HAs after allogeneic stem cell transplantation, https://doi.org/10.1182/asheducation-2015.1.378. Transfusion reactions (TRs) occurring during inpatient admissions (excluding emergency room and outpatient visits) from 1/1/2010-31/12/2015 were included. Splenectomy can be recommended to patients without contraindications. Further studies to better understand the pathophysiology of TA-TMA are needed. A very important feature of all antibodies responsible for causing a haemolytic transfusion reaction is its invitro activity at 37C. Differential diagnosis of delayed haemolytic transfusion reactions includes latent sources of infection, autoimmune haemolytic anaemia, cold agglutinin disease, nocturnal paroxysmal haemoglobinuria, bleeding, mechanical destruction of red blood cells, for example, artificial heart valves and TTP. The safety of body cells is enabled by factors that regulate complement activity present in plasma and on cells of various tissues, including red blood cells. The specificity of the antibodies potentially responsible for intravascular and extravascular haemolysis is shown in Table 4. Therefore, HA can also occur as a consequence of alloantibodies against non-ABO RBC antigens and has the same pathophysiology as PLS.8,20,21 The Rhesus (Rh) system is the one most frequently described. This additional mechanism occurs when recipients red blood cells are destroyed by a reaction called bystander immune cytolysis. To exclude any underlying alloantibody, which carries the risk of delayed hemolytic transfusion reactions, time-consuming absorption techniques and/or knowledge of blood-group genotype are needed. Membrane inhibitor of reactive lysis (MIRL) (CD59) and decay accelerating factor (DAF) (CD55) are essential to protect red blood cells from haemolysis. To date our community has made over 100 million downloads. In the laboratory setting, anti-Jka antibodies are called insidious antibodies because they are often difficult to detect due to their low concentration, and yet they can cause a severe haemolytic complication [41]. Delayed immune Acute immune-mediated transfusion reactions occur immediately following, or within 24 hours of, transfusion. /CreationDate (D:20161012131918-04'00') Sometimes, isohemagglutinins against recipient ABO blood group antigens can be detected. /Producer (Apache FOP Version 1.0) Primarily, calcineurin inhibitors and/or sirolimus should be reduced in dose or discontinued if alternative drugs for the prevention or treatment of GVHD can be administered (eg, steroids, mycophenolate mofetil). However, it is worth noting that despite the low intensity of haemolysis, the survival time of red blood cells after transfusion is significantly reduced [2]. /Creator (Apache FOP Version 1.0) CP declares that he has no competing interests. Interesting clinical point of view are antibodies from the Kidd system. >> Haemolytic post-transfusion reaction is caused by accelerated destruction of erythrocytes by immunological incompatibility between the donor and the recipient. Clinically, this is manifested by unexpected bleeding and/or a decrease in blood pressure. Hemolytic transfusion reaction. A hemolytic transfusion reaction is a serious complication that can occur after a blood transfusion. The reaction occurs when the red blood cells that were given during the transfusion are destroyed by the person's immune system. When red blood cells are destroyed, the process is called hemolysis. There are other In contrast, extravascular haemolysis is less dramatic, with a rate of destruction of red blood cells of approximately 0.25ml/h/1kg of recipients body weight. Hemolytic disease of the fetus and newborn is an alloimmune hemolysis caused by maternal antibodies in the neonate's plasma, is most commonly anti-Rh, and are uncommon. 0 /Length 11 0 R * Conditions that can occur alone or in combination in HSCT recipients. CCL2 is mainly a chemotactic and activating factor for monocytes [1, 12]. A report issued by the Quebec Haemovigilance System covering 5 years of observation described 47 ABO incompatibility reactions, 55 cases of acute haemolytic transfusion reaction and 91 cases of delayed transfusion reaction in reference to 7059 all reported transfusion reactions. Additionally, RhD alloimmunization through platelet transfusions should be prevented either by choosing platelet concentrates from RhD-negative donors or through prophylaxis with anti-RhD immunoglobulins. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. London, SW7 2QJ, Receptors for complement activation products C3a and C5a are found on many cells: monocytes, macrophages, neutrophils, platelets, endothelium and smooth muscle. Why this happens isn't known. However, transfused blood is a foreign In general, AD can affect every organ and occur alone or in combination.42 Autoimmune cytopenias after HSCT (including AIHA, immune thrombocytopenia, and immune neutropenia, or a combination of them) occur frequently.45-47 Incidence ranges from 1.3% to 4.4% and the risk factors for the development of AIHA are transplantation from an unrelated donor, development of chronic GVHD and a nonmalignant primary disease.45 Disease course is variable, ranging from spontaneous remissions to life-threatening and even fatal hemolysis. However, transfusion requirement in acute AIHA can be a medical emergency and must not be delayed as RBC transfusions can be lifesaving. Identification is critical because of the high probability of a second patient receiving the wrong blood product at the same time. Its presence to some extent affects some clinical differences between extravascular and intravascular haemolysis [23]. Udani etal. In contrast to solid organ transplantation, donor-recipient ABO incompatibility is not an impediment for HSCT and occurs in 30%-50% of transplants.7,8 In major ABO-incompatible HSCT, the patient has preformed antibodies (ie, isohemagglutinins) against A and/or B antigens expressed on the donor's RBC. 0000000845 00000 n Antibodies that cause a delayed haemolytic transfusion reaction are IgG molecules that are binding or non-binding for complementary components. The presence of O2 leads to oxidation of NO to NO3 and oxidation of Fe2+to Fe3+and the formation of methaemoglobin. The reaction of anti-HLA antibodies with leucocytes caused complement activation, which resulted in haemolysis of the patients red blood cells sensitive to the complement [59]. WebIn immune hemolytic anemia, your immune system destroys your red blood cells. The presence of fibrinogen degradation products from an absorbing haematoma can be interpreted as a DIC symptom. Search for other works by this author on: 2016 by The American Society of Hematology. The three main types of immune hemolytic anemia are autoimmune, alloimmune, and drug-induced. DAF regulates C3a-converting activity. Table 2 presents the point algorithm for the diagnosis of acute disseminated intravascular coagulation. The effect of intravascular haemolysis described above may be very similar to the side effect caused by transfusion of first-generation stromal haemoglobin solutions. Laboratory testsmainly serologicalare crucial for the diagnosis of an early haemolytic reaction. 38 0 obj<> endobj The C4b2a complex has proteolytic properties and is called C3 convertase. 5 0 obj They can also be partially absorbed and then the integrity of the cell membrane is disturbed by the loss of proteins and lipids, which changes its osmotic properties. Frequency varies according to reports and may be seen in up to 35% of patients, depending on the diagnostic criteria and definitions.26-28 In contrast to thrombotic thrombocytopenic purpura (TTP), where an inborn or acquired deficiency of the von Willebrand factor multimer cleaving protease ADAMTS13 is the cause, the exact etiology and pathophysiology of TA-TMA remain unclear.25,28-30 Clinical presentation is heterogeneous and it is likely that TA-TMA represents a clinical syndrome that is a common end product of different pathophysiologic processes involving also the coagulation system. NH-DSTRs are associated with a longer LOS when compared with all other TRs. They are mediated by the interaction of recipient antibodies to foreign antigens contained in any allogeneic blood products. Platelets in additive solutions contain less donor plasma and thus less isohemagglutinins, and should therefore be preferred to standard plasma-suspended platelets. Haemoglobin released from red blood cells also reacts nephrotoxically with nitric oxide (NO), damaging the epithelial cells of the renal tubules and the stroma that remains after their breakdown [33, 34]. 0000000925 00000 n Additionally, each center should define policies and standard operating procedures for the prevention and management of complications after ABO-incompatible HSCT (Table 3).19 Definite ABO blood group assignment should be done after a transfusion-independent interval, full engraftment, remission of the underlying disease, and in close collaboration with the treating physicians. By Osaro Erhabor, Tosan Erhabor, Teddy Charles Adias By Vivian Gonzaga, Bruna Policiquio, Cristiane Wences By Vernica Valdivieso-Gmez, Javier Garrancho-Prez, IntechOpen Limited WebFebrile Non-Hemolytic Transfusion Reaction (FNHTR): FeverOR chills and rigors occurring within 4 hours of transfusion.Signs and symptoms include fever (greater than or equal to38C/100.4F oral and a change of at least 1C/1.8F) frompre-transfusion value) or chills/rigors.Acute Hemolytic Transfusion Reaction (AHTR): Hemolysisoccurring within Hemolysis ranges from being asymptomatic and harmless to therapy resistant, life threatening, and even fatal. Most often intravascular haemolysis is the result of the destruction of red blood cells by the complement system, stimulated by the presence of alloantibodies or autoantibodies. The above improvements, however, did not significantly affect the elimination of mistakes made in hospitals leading to transfusion of inappropriate blood to the patient. In different people, antibodies with a particular specificity most often occur in the same class of immunoglobulins and have a similar heat amplitude, for example, anti-A, anti-B and anti-AB from the ABO system often belong to both IgM and IgG classes, they bind complement and have an extended thermal amplitude of up to 37C. As opposed to other reviews of HAs, most often structured according to the pathophysiology of the hemolysis (ie, immune vs nonimmune), in this review, we have followed the timeline of the transplantation process and have discussed the investigation, differential diagnosis, and management at the time points during transplantation when HA most commonly occur. Table 5 presents features of delayed haemolytic transfusion reaction and the time of their occurrence. microspherocytes? However, this complication is rare and predominantly accompanies intravascular haemolysis, but in recipients who have received non-compliant blood in the ABO system, it occurs even in 25% of cases [1]. A negative DAT result does not exclude haemolysis, it may mean that the transfused blood cells have been destroyed by alloantibodies or the method used is not very sensitive. 40 0 obj<>stream The mechanism of bystander haemolysis is similar to the destruction of blood cells in patients with paroxysmal nocturnal haemoglobinuria [57, 58]. Search for other works by this author on: An Updated Report by the American Society of Anesthesiologists Task Force on Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration, A Tool to Screen Patients for Obstructive Sleep Apnea, ACE (Anesthesiology Continuing Education), https://doi.org/10.1097/00000542-194601000-00029, 2022 American Society of Anesthesiologists Practice Guidelines for Management of the Difficult Airway, 2023 American Society of Anesthesiologists Practice Guidelines for Preoperative Fasting: Carbohydrate-containing Clear Liquids with or without Protein, Chewing Gum, and Pediatric Fasting DurationA Modular Update of the 2017 American Society of Anesthesiologists Practice Guidelines for Preoperative Fasting, Practice Guidelines for Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration: Application to Healthy Patients Undergoing Elective Procedures, Reducing Noninfectious Risks of Blood Transfusion, Use of Uncrossmatched Erythrocytes in Emergency Bleeding Situations. Thereby, there is a transfer of plasma, red blood cells, and immunocompetent cells from the donor to the recipient, possibly leading to HA, due to red blood cell incompatibility. 0000000016 00000 n Bilirubin concentration depends on the severity of haemolysis and liver function. Causality is not established by this analysis, nor is there a biologic rationale for a NH-DSTR to directly impact LOS. [62]. These reactions can occur acutely or in a delayed timeframe, while the sensitizing antibody may derive from the host or be passively acquired. 0000007661 00000 n Factors that can affect the increase in the number of delayed haemolytic reactions include correctness in carrying out serological tests, longer survival of patients after transfusions and an increase in the number of transfused blood components. A retrospective review of a transfusion reaction database was undertaken at a large academic hospital in Toronto, Canada. However, clinicians should be aware that titer determination is not standardized and shows a wide intra-individual variability. Blood cells connected to this receptor are destroyed in the process of antibody-dependent cytotoxicity. In this condition, your immune system makes antibodies (proteins) that attack your red blood cells. The distribution of TRs (Figure 1) included 562 (71.8%) non-anti-RBC TRs and 221 (28.2%) anti-RBC TRs. Anti-erythroid antibodies are the classical marks of serologic and hemolytic transfusion reactions. [9] showed that the formation of warm autoantibodies after the onset of DHTR is relatively common. Since IL-1 and IL-6 affect proliferation and differentiation of -lymphocytes, the synthesis of these two cytokines enhances the synthesis of allo- and autoantibodies, which are often involved in the formation of delayed haemolytic transfusion reaction [1, 24, 25]. Copyright 2023 American Society of Anesthesiologists. How do I approach ABO-incompatible hematopoietic progenitor cell transplantation? They may be similar to delayed haemolytic reactions. This is defined as a combination of both major and minor ABO incompatibilities along with the risk of their consequences, and thus clinicians have to be aware of all the above-described complications. Some transfusion services measure anti-A and/or anti-B titers, and thus units with high titers of isohemagglutinins can be transfused to ABO-identical recipients. WebParticipation in the NHSN Hemovigilance Module requires reporting of all adverse transfusion reactions and reaction-associated incidents that occur for patients transfused at or by your facility as well as a monthly summary of components transfused or discarded and patient samples collected for type and screen or crossmatch. Hemolytic anemia (HA) is a condition in which the patient's red blood cells (RBCs) are prematurely destroyed. Asterisk with author names denotes non-ASH members. Management consists primarily of adequate supportive care with transfusions of RBCs compatible with both the recipient and the donor. Microangiopathic HA is characterized by the presence of anemia, low platelets, and schistocytes in a blood smear. The severity of this abnormality varies greatlyfrom asymptomatic increase in urea (BUN) and serum creatinine up to complete anuria. In refractory patients, rituximab and other immunosuppressive drugs including combinations can be added.45,47 Immunosuppression has to be balanced against the risks of disease relapse and infections. [60] compared the sensitivity of DAT performed by technique using monospecific IgG antiglobulin, flow cytometry and antibody elution. Concomitant hypotension and intravascular coagulation syndrome may increase renal impairment. If the activation of coagulation is not timely inhibited, the resulting clots will block the blood supply to vital organs, which will be manifested in their failure. In differential diagnosis, attention should also be paid to non-immune reasons related to improper blood storage, transfusion of red blood cells through a small needle diameter, etc. However, there is no accepted and clear definition for high-titer antibodies. When acute reactions occur they are typically mild, with the most common reactions including fever and rash. <<488cdda8e0677b47a7accfabb5999f1d>]>> WebFebrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reaction. Type of laboratory tests and the location of their performance in the case of early transfusion reaction. Schonewille etal. Patients have clinical and laboratory evidence of HA, a positive DAT (usually positive for IgG C3d in warm-type and positive for C3d in cold-type AIHA), and a positive, panreactive indirect antiglobulin test. The nature of the reaction may not be immediately apparent, It should be emphasised that in patients with an early reaction due to ABO incompatibility, exchange transfusion may reduce the risk of serious complications or death. 0000002243 00000 n HLA antigens found on leukocytes and plasma proteins), while red blood cells are only close to this immunological confusion [56]. Elevated LDH is always observed with intravascular haemolysis, not always with extravascular haemolysis. There is an association between TA-TMA and GVHD, although causality remains to be proven. Performing DAT in the red blood cell eluate, its sensitivity was 1%. We follow the timeline of the transplantation process and discuss investigations, differential diagnosis, and prophylactic measures including graft processing to avoid hemolysis in case of ABO incompatibility.
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