Although infrequent, non-immune transfusion reactions, including haemolysis, transfusion-associated sepsis, and circulatory overload, should be considered in the differential diagnosis. 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. It is mainly haemolysis that is responsible for the destruction of transfused donor blood cells by antibodies present in the recipient, but in rare cases, destruction may be caused in recipient blood cells by donor antibodies present in transfused plasma or platelet concentrate [1]. The type of laboratory tests performed for early transfusion haemolytic reactions is shown in Table 7. Most of the cells coated by the complement C3b component are destroyed by liver macrophages, that is, by Kupffer cells, while the cells coated with antibody molecules are mainly destroyed by spleen macrophages. 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). Nevertheless, major ABO-incompatibility needs to be considered and appropriately ruled out in case of acute reactions after transplantation. Another cause for haemolytic transfusion reaction may be a secondary immune response in patients who have developed alloantibodies during previous transfusions of blood components or pregnancy. Transfusion Reactions WebGlucose-6-phosphate dehydrogenase (G6PD) deficiency. 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. IL-1 concentration and IL-6 produced by monocytes in response to red blood cells coated with IgG antibodies increase progressively within 24h to a concentration of 100pg/ml. 5 0 obj 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]. However, this is rarely done and potential bleeding risks have to be balanced against the diagnostic benefits of this procedure.28 Unfortunately, there are no controlled trials and thus there is no consensus on the management of TA-TMA. Type of laboratory tests and the location of their performance in the case of early transfusion reaction. They activate the complement system to the stage of binding of the C3b component, causing extravascular haemolysis. Failure of central and/or peripheral tolerance is believed to be involved in the escape of auto-reactive lymphocytes, thus leading, if uncontrolled, to the development of ADs. Laboratory tests that help to differentiate haemolysis include determination of free haemoglobin in the blood and urine, haptoglobin and lactate dehydrogenase (LDH) and bilirubin. Transfusion reactions (TRs) occurring during inpatient admissions (excluding emergency room and outpatient visits) from 1/1/2010-31/12/2015 were included. Risk factors, including endothelial damage by conditioning agents (including irradiation), medications (immunosuppressants like calcineurin inhibitors and sirolimus), and viral infections have been identified. This process is reversible, so SNO-Hb releases NO, which is transported to endothelial receptors, where it participates in the regulation of vascular wall tone and blood flow. All rights reserved. Anemia, reticulocytopenia, and a bone marrow lacking erythroid precursors are clues for the diagnosis of PRCA in the setting of major ABO-incompatible HSCT. Hemolytic anemia (HA) is a condition in which the patient's red blood cells (RBCs) are prematurely destroyed. It is manifested by a rapid decrease in haemoglobin, haemoglobinemia and haemoglobinuria and can potentially be life threatening [2]. Only in the case of rare haemolytic reactions due to anti-Lea it was shown that the coated cells are destroyed by the spleen macrophages very slowly and in the event of transfusion of large volumes of red blood cells, they become inefficient. Within the anti-RBC TRs, 159 (71.9%) were classified as NH-DSTRs. Hemolytic Anemia: Evaluation and Differential Diagnosis In case of preformed alloantibodies (through transfusions or pregnancy) and a major RhD incompatibility, delayed HA may result. 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. DHTR can be identified in these patients by the presence of antigen on the transfused red blood cells to which the antibodies may be directed. Acute hemolysis may also rarely occur after minor ABO-incompatible HSCT through transfer of high-titer donor isohemagglutinins contained in the graft or in recipients with small blood volume (pediatric patients). Hematology Am Soc Hematol Educ Program 2015; 2015 (1): 378384. Catheterisation of the pulmonary artery helps to monitor the situation. Fibrin creates blood clots in the light of small vessels trapping the platelets. 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. ] _ZE|U m.=KAa M 3i4 d30qin [1 Z4L=x6lfpE FLbk 00 We also refer to other sources.2-4 Drug-induced HA should always be considered, especially due to antimicrobial agents (eg, dapsone, penicillins, and cephalosporins) and immunosuppressants [calcineurin-inhibitors and sirolimus, which are the most frequently used drugs for graft-versus-host disease (GVHD) prophylaxis].5 Hemolysis due to passive transfer of antibodies from a high-titer type O blood product and hemolytic transfusion reactions (acute and delayed) following transfusion errors or due to non-ABO-RBC alloantibodies need to be excluded. [62]. Transfusion Reactions: Practice Essentials, Pathophysiology, Etiology Febrile non-hemolytic transfusion reaction (FNHTR) Febrile non-hemolytic transfusion reactions are the most common reaction reported after a transfusion. FNHTR is characterized by fever or chills in the absence of hemolysis (breakdown of red blood cells) occurring in the patient during or up to 4 hours after a transfusion. Delayed immune CLL indicates chronic lymphocytic leukemia; CVID, common variable immunodeficiency syndrome; G6PD, glucose-6-phosphate dehydrogenase; GVHD, graft-versus-host disease; PNH, paroxysmal nocturnal hemoglobinuria; and SAA, severe aplastic anemia. Delayed red cell engraftment due to host anti-donor isohemagglutinins may occur. However, there is no accepted and clear definition for high-titer antibodies. Receptors for complement activation products C3a and C5a are found on many cells: monocytes, macrophages, neutrophils, platelets, endothelium and smooth muscle. This phenomenon is called delayed serologic transfusion reaction (DSTR) and should be differentiated from delayed haemolytic transfusion reaction [9]. Patients with liver failure are a special problem. Non-hemolytic normocytic anemia: Pathology review 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. However, there is a danger of bleeding. The test should be performed on serum/plasma samples taken before and after transfusion. Renal failure and DIC are also more commonly associated with intravascular haemolysis. Drop in blood pressure is much more common in patients with intravascular than extravascular haemolysis. Distinction of Hemolytic and Nonhemolytic Transfusion Reactions Red blood cells can be absorbed and completely digested inside the macrophage. Laboratory tests show anaemia, increased LDH and bilirubin, decreased haptoglobin and higher white blood cell counts in post-transfusion haemolytic reactions. It is worth noting that the estimation of the frequency of haemolytic reactions depends on the number of transfusions in a given centre. Hemoglobin monitoring (sometimes repetitively in 1 day in case of severe hemolysis), a full blood count including reticulocytes, blood smear (schistocytes? For exchange transfusion, red blood cells without an antigen should be used against which the patient has developed alloantibodies. They may be similar to delayed haemolytic reactions. 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. UR\#? hemolytic transfusion reaction - Medical Dictionary TRALI can be delayed by a few hours. In some patient groups, it may be difficult to recognise a delayed haemolytic transfusion reaction. DAF regulates C3a-converting activity. Why this happens isn't known. In those with concurrent hemolysis, the red blood cell (RBC) breakdown may be severe enough to command supportive care. After 24 incubations with incompatible red blood cells, monocytes show a significant increase in CD44 levels. %PDF-1.4 Similar reactions to anti-A and anti-B come from anti-PP1Pk, anti-P1 and anti-Vel. They are mediated by the interaction of recipient antibodies to foreign antigens contained in any allogeneic blood products. Membrane inhibitor of reactive lysis (MIRL) (CD59) and decay accelerating factor (DAF) (CD55) are essential to protect red blood cells from haemolysis. But until then, HTRs will remain the most important adverse post-transfusion reaction. Conflict-of-interest disclosure: Holbro has received research funding from CSL Behring and Novartis, and has consulted for Teva and Amgen; and Passweg declares no competing financial interests. D indicates donor ABO blood group; PLT, platelet; R, recipient ABO blood group; and RBC, red blood cell. In contrast, the presence of antigens from the Rh, Kell, Kidd and Duffy systems on the surface of red blood cells is determined in the range of 103104 per cell [12]. WebA hemolytic transfusion reaction is a serious complication that can occur after a blood transfusion. Treatment and prevention of DIC during haemolytic transfusion reaction is controversial. Red blood cell transfusion can also stimulate the production of alloantibodies without the occurrence of haemolysis. Platelets in additive solutions contain less donor plasma and thus less isohemagglutinins, and should therefore be preferred to standard plasma-suspended platelets. The starting point is the antigen-antibody complex present on the surface of the cell membrane [14, 15]. WebIn immune hemolytic anemia, your immune system destroys your red blood cells. MIRL inhibits membrane attack complex [15, 17]. AB plasma is the universal donor source. Hemolysis during and after HSCT can occur at different time points, ie, even weeks or months after transplantation, and may have several causes (Figure 1). 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. Prompt recognition of an immune-mediated transfusion reaction is fundamental to improving patient outcome. 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. In those with concurrent hemolysis, the red blood cell (RBC) breakdown may be severe enough to command supportive care. endobj However, transfusion requirement in acute AIHA can be a medical emergency and must not be delayed as RBC transfusions can be lifesaving. [51] carried out in pooled platelet concentrates of whole blood groups showed that 60% of them had anti-A titres of at least 64 [51]. 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: When acute reactions occur they are typically mild, with the most common reactions including fever and rash. Hemolysis ranges from being asymptomatic and harmless to therapy resistant, life threatening, and even fatal. Concentration of fibrinogen/fibrin degradation markers (FDP; D-dimery), Anti-A, -B, -AB, -H in the Bombay phenotype, Antibody titres below detection threshold, Acceleration of transfused blood cells destruction, Post-transfusion testing of blood samples: DAT and screen of antibodies positive, Increase in antibody titre; donated blood cells coated with antibodies, Destruction of donor blood cells in reticuloendothelial system and/or liver, DAT may be positive, eluate testing may show presence of alloantibodies or panagglutination, Alloantibodies not specifically associated with autologous red blood cells or produced warm antibodies, Increased bilirubin concentration medium/slow, The presence of haemoglobin in plasma and/or urine, Normal saline and/or 5% dextrose 200ml/m, Platelet1 unit platelet/10kg or 1 unit apheresis platelet, Intravenous immunoglobulin (not standard therapy). They may interact with CR1 and CR3 receptors on macrophages and consequently undergo phagocytosis. Blood Safety Basics | CDC *All RBC concentrates should be -irradiated (25-30 Gy) and leukocyte reduced. 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. One of the reasons for this haemolytic reaction is the binding of the C567 complement complex, activated in an immune reaction, to the membrane of red blood cells not participating in the reaction but located in the vicinity [56]. Adverse Effects of Blood Transfusion Transfusion Reactions trailer These diseases may relapse and thus HA can be a possible clinical manifestation either of relapse or of graft failure. The study showed that DAT could only indicate 10% of antibody coated cells [61]. MFk t,:.FW8c1L&9aX: rbl1 Table 8 presents changes in laboratory indicators in transfusion haemolytic reactions [56]. 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. For any urgent enquiries please contact our customer services team who are ready to help with any problems. The C3b and C3d components bind with the red blood cell membrane and in many cases the complement cascade process ends. Delayed reactions occur days to weeks after the transfusion and include delayed haemolytic transfusion reactions, transfusion-associated graft-versus-host disease, and post-transfusion purpura. Therefore, if possible, blood without this antigen should be selected [41]. Although the mechanism of the lectin route may be the reason for the invivo ineffectiveness of the use of monoclonal and recombinant antibodies, which are thus eliminated from the body before they fulfil their function, for example, anti-D Ig for prevention purposes in RhD maternal-foetal conflict [16]. In addition, their degradation products (fibrinogen/fibrin degradation products (FDP)) resulting from the breakdown of fibrinogen and fibrin exhibit anticoagulant properties, inhibit platelet function, act as cytotoxic vascular endothelium and increase capillary permeability, further disrupting haemostasis mechanisms [26]. Hemolytic anemia (HA) is a condition in which the patient's red blood cells (RBCs) are prematurely destroyed. Antibodies that cause a delayed haemolytic transfusion reaction are IgG molecules that are binding or non-binding for complementary components. In ABO incompatibility, in which anti-A, anti-B and anti-AB antibodies activate complement leading to intravascular haemolysis, a large amount of tumour necrosis factor- (TNF) and interleukins CXCL8 (IL-8) and CCL2 are released into the plasma (MCP-1) [19, 20, 21]. WebFebrile non-hemolytic transfusion reaction (FNHTR): This is defined as an acute increase in body temperature >1C within 4 hours of the end of a transfusion and a temperature of >39C or 102.5F that cannot be explained by other Haemolysis may also occur due to non-immunological reasons, such as thermal, osmotic or mechanical damage to the transfused blood; bacterial infection or extremely rare and blood transfusion from a donor with congenital haemolytic anaemia due to deficiency of glucose-6-phosphate dehydrogenase [2]. However, many studies show discrepant results regarding transplant outcomes and it is most likely that ABO blood-group incompatibility is not important for transplant outcome.7,8, Hemolytic complications due to ABO incompatibility. 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. The course is acute, dynamic, with thrombocytopenia, increased concentration of fibrin degradation products, prolonged prothrombin time (PT), extended partial thromboplastin time after activation (activated partial thromboplastin time (APTT)) and hypofibrinogenaemia. The alternative path of complement activation and the lectin path of complement activation do not play a role in the destruction of red blood cells. University of Alabama at Birmingham Hospital. Andreas Holbro, Jakob R. Passweg; Management of hemolytic anemia following allogeneic stem cell transplantation. How? Changes in laboratory indicators in haemolytic transfusion reactions [56]. This review highlights the current knowledge on HA after allogeneic HSCT, particularly due to ABO incompatibility. Clinically, this is manifested by unexpected bleeding and/or a decrease in blood pressure. Diagnosis of post-transplant AIHA has to be distinguished from disease relapse, graft failure, drug- and treatment-related toxicity, infection, and GVHD. No relevant conflicts of interest to declare. A contrasting example is the Lua antigen and anti-Lua antibodies. Finally, current therapeutic approaches for both TA-TMA and post-HSCT autoimmune HA, which are associated with high morbidity and mortality, are discussed. Non-immune Hemolysis: Diagnostic Considerations Acute transfusion reactions range from bothersome yet clinically benign to life-threatening reactions. 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 In case of a positive DAT, elution against group A and/or B reagent RBCs (instead of the usual O group panel) can be helpful to support the diagnosis. Initial symptoms of haemolytic transfusion reactions. To understand that hemolytic anemia (HA) is frequent after hematopoietic stem cell transplantation (HSCT), To discuss different etiologies of HA during and after allogeneic HSCT, To know how to approach and investigate HA in this situation for an accurate diagnosis, To know the prophylactic measures to reduce the extent of hemolysis in case of ABO-incompatible HSCT and to know currently available therapeutic options, To know the special transfusion requirements of patients before, during, and after HSCT, implying a close collaboration between clinicians, transplant physicians, and transfusion services. Approximately one-third of patients who were examined 25days after the onset of the reaction presented a positive DAT due to autoantibodies with broad specificity [9]. Frequency of transfusion reactions from January 1, 2010 to December 31, 2015. IL-1ra (receptor antagonist) is produced in extravascular haemolysis, which is an IL-1 receptor antagonist. The re-determination of the ABO and RhD blood group of the recipient before and after the transfusion and in the donors blood will exclude errors in the identification of the recipient or blood sample (wrong blood in tube (WBIT)). Therefore, prior to conducting laboratory tests of donor blood, bacteriological examination of the component remaining after the transfusion cessation should be conducted. @~ (* {d+}G}WL$cGD2QZ4 E@@ A(q`1D `'u46ptc48.`R0) The specificity of the antibodies potentially responsible for intravascular and extravascular haemolysis is shown in Table 4. 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]. Often, the clinical manifestations of haemolytic reactions are not clear, and the cause of the complication should be differentiated with bacterial infection. Its occurrence and severity, in addition to the class of antibodies, is also affected by the number of antigenic determinants with which the antibodies react. In addition, the widespread introduction of automation and computerisation to pre-transfusion studies, which significantly limits the possibility of errors in serology laboratories and blood banks. JAW declares that he has no competing interests. Hemolytic transfusion reaction: MedlinePlus Medical Splenectomy can be recommended to patients without contraindications. For patients with ongoing haemorrhage choosing a blood for transfusion may be difficult. WebFebrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reaction. The mechanism of appearance of intravascular symptoms has not been fully explained, because although some of the antibodies bind complement components, their reactions end with C3 components. Febrile non-hemolytic transfusion reaction - Wikipedia The increase in cytokine release may also be due to the interaction of Fc R1 receptors with IgG molecules associated with red blood cells. 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. 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. [20] showed invitro that in the case of ABO incompatibility, monocytes are directly involved in the formation of acute haemolytic transfusion reaction [15]. 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. Parvovirus B19 infection has to be excluded. 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. The effect of intravascular haemolysis described above may be very similar to the side effect caused by transfusion of first-generation stromal haemoglobin solutions. The patient's history, knowledge of the performed transplant procedure (type and intensity of conditioning, donor and recipient ABO blood group, graft source, and GVHD prophylaxis and therapy) and the patient's transfusion history are essential. Therefore, pre-transfusion tests may not always detect the presence of antibodies. Intravascular haemolysis is characterised by the destruction of red blood cells at a rate of about 200ml of transfused cells within 1h of transfusion. Haemolytic post-transfusion reaction is caused by accelerated destruction of erythrocytes by immunological incompatibility between the donor and the recipient. Hematopoietic stem cell transplantation (HSCT) is a potentially curative and increasingly used treatment approach for different malignant and nonmalignant diseases, including entities associated with HA, such as chronic lymphocytic leukemia with autoimmune HA (AIHA), paroxysmal nocturnal hemoglobinuria, and sickle cell disease.1 HA can develop after HSCT; however, HSCT can still be considered for the treatment of severe, therapy-resistant AIHA. The presence of these isohemagglutinins and the involvement of the donor's and recipient's immune system are responsible for hemolytic complications (Table 2). 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. Such a blood cell, after being released from the macrophage, circulates in the blood as a spherocyte, whose survival is short. Copyright 2023 American Society of Anesthesiologists. microspherocytes? Evidence for treatment of post-transplant AIHA is lacking and available data arise from single case reports or case series. The most common cause of haemolytic transfusion reactions is the immunological destruction of red blood cells resulting from the reaction of antibodies in the recipients blood and the antigens present on the transfused donors blood cells to which these antibodies are made. Microangiopathic HA is characterized by the presence of anemia, low platelets, and schistocytes in a blood smear. Hemolysis can be severe, even fatal, and persists until all the recipient RBCs are replaced by transfused or donor-derived RBCs. A characteristic feature of the cell membrane of these blood cells is the lack or weak expression of the CD55 (DAF) and CD 59 (MIRL) proteins, which are complement inhibitors. DICdisseminated intravascular coagulation; FFPfresh frozen plasma. Spath etal. Hemolysis in DHTR can be severe, because both the transfused and autologous red blood cells may be destroyed (so-called bystander hemolysis); DHTR In addition, hypertension and proteinuria can be the early signs of TA-TMA, although these manifestations are encountered frequently in patients after HSCT.26,27,34,35 Soluble membrane attack complex (sC5b-9) may be elevated and is associated with a poor prognosis.30 Diagnosis can be confirmed by renal biopsy, which shows typical histologic findings, although there is little correlation between clinical and pathologic diagnosis. In the annual report Serious Hazards of Transfusion (SHOT), published in England, in 2017, 42 haemolytic transfusion reactions were reported in reference to 3230 of all reactions observed following transfusion of blood components, of which 13 cases of acute haemolytic transfusion reaction and 29 cases of delayed haemolytic reaction (including 6 cases of hyperhemolysis) were reported. Positive DAT with anti-IgG reagents or with anti-IgG and anti-C3 reagents is generally seen as two red blood cell populations. In the case of minor incompatibility both immediate and delayed hemolysis can occur.21 In this case, management is similar to ABO-incompatibility. [9] showed that the formation of warm autoantibodies after the onset of DHTR is relatively common. Proinflammatory cytokines affect blood coagulation and fibrinolysis, for example, TNF- and IL-1 increase TF expression and inhibit thrombomodulin (TM) expression on vascular endothelial cells [28]. It should be noted that an increase in body temperature and white blood cell count, typical for DHTR, can be interpreted as a sign of infection. Licensee IntechOpen. Furthermore, transfusion of incompatible plasma is associated with increased transplant-related mortality due to an increased risk of infection, veno-occlusive disease, and multi-organ failure.22,23 Therefore, both donor- and recipient-compatible plasma should be transfused after HSCT to avoid hemolysis, due to the passive transfer of isohemagglutinins against recipient and/or donor RBC antigens (Table 3). In the case of haemolysis of red blood cells, the free haemoglobin released from them reacts with NO much faster and more strongly than Hb inside cells [35]. Search for other works by this author on: 2016 by The American Society of Hematology. {{{;}#tp8_\. /Length 11 0 R Bilirubin concentration depends on the severity of haemolysis and liver function. TNF- is released first, its elevated concentration is already detected within first 2h. It carries a pro-inflammatory potential that is responsible for fever, leukocyte activation, stimulation of procoagulant activity, increased antibody production and vascular wall permeability [22]. Investigation may be difficult because the differential diagnosis is often broad.
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hemolytic vs non hemolytic transfusion reaction