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 ??accessibility.screen-reader.external-link_en_US?? They have surface receptors that recognise antibody classes and subclasses, and complement components, of which the Fc R1 receptor is specific for red cells coated with antibodies [1]. Andreas Holbro, Jakob R. Passweg; Management of hemolytic anemia following allogeneic stem cell transplantation. [20] showed invitro that in the case of ABO incompatibility, monocytes are directly involved in the formation of acute haemolytic transfusion reaction [15]. Pyruvate kinase deficiency. In two countries, Sweden and Finland, which have implemented national identification systems, this frequency was 1 for 1986 samples [61]. Concomitant hypotension and intravascular coagulation syndrome may increase renal impairment. Positive reactions with allogeneic blood cells are accompanied by positive auto control of the patients red blood cells. Haemoglobinemia is not diagnosed in the serum of these patients due to jaundice, often direct antiglobulin reaction (DTA) is positive and elevated bilirubin and LDH are found. Steroids should be administered at a dosage of 1-2 mg/kg. WebThe Distinction of Hemolytic and Nonhemolytic Transfusion Reactions Edward B. Flink Anesthesiology January 1946, Vol. Intravascular hemolysis mediated by complement-fixing London, SW7 2QJ, How long does it take for a hemolytic transfusion to occur? The severity of this abnormality varies greatlyfrom asymptomatic increase in urea (BUN) and serum creatinine up to complete anuria. 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. /Producer (Apache FOP Version 1.0) It also occurs for non-immunological reasons: thermal, osmotic or mechanical damage and bacterial infection. WebTransfusion Reactions Also known as AHTR (acute hemolytic transfusion reaction) DHTR (delayed hemolytic transfusion reaction) FNHTR (febrile non-hemolytic /N 3 In this condition, your immune system makes antibodies (proteins) that attack your red blood cells. Such a blood cell, after being released from the macrophage, circulates in the blood as a spherocyte, whose survival is short. Catheterisation of the pulmonary artery helps to monitor the situation. Historical research results indicate that the frequency of haemolytic transfusion reactions falls between 1:10,000 and 1:50,000 transfused blood components [3, 4]. 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. 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. Further studies are needed to confirm this association. Identification is critical because of the high probability of a second patient receiving the wrong blood product at the same time. This mechanism is called the classic pathway for complement activation and is shown in Figure 1. [60] compared the sensitivity of DAT performed by technique using monospecific IgG antiglobulin, flow cytometry and antibody elution. When acute reactions occur they are typically mild, with the most common reactions including fever and rash. These errors are the most common cause of ABO incompatible transfusions, threatening the patients life. 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]. Delayed immune Haemolysis can be endogenous (usually acute) and exogenous with macrophages in the reticuloendothelial system of spleen or liver (delayed). A review of NH-DSTRs was thus performed in a large academic hospital (34,000 RBC dispensations annually). However, the symptoms in some recipients, or the occurrence of a reaction already during a blood transfusion and haemoglobinuria, indicate that the destruction of blood cells also takes place inside the vessel. 0000004992 00000 n Heparin is recommended because it additionally acts as an inhibitor of the complement activity and limits haemolysis. In some patient groups, it may be difficult to recognise a delayed haemolytic transfusion reaction. In case of preformed alloantibodies (through transfusions or pregnancy) and a major RhD incompatibility, delayed HA may result. <<488cdda8e0677b47a7accfabb5999f1d>]>> Sometimes, isohemagglutinins against recipient ABO blood group antigens can be detected. Infections, which occur frequently in HSCT recipients as a consequence of their disease, conditioning, and immunosuppression, may play an additional role in the pathogenesis of post-transplant ADs.42. Suggested transfusion guidelines for patients undergoing ABO-incompatible HSCT6,8. 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]. 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. Is Whole Blood Poised for a Return in Civilian Trauma? For example, for 70kg recipient, about 18ml of transfused red blood cells are destroyed per hour. 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. 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. One of them, which does not react with diagnostic antibodies, is the recipients autologous blood cells, the other population is antigenically incompatible transfused donor cells, not yet removed from the recipients circulation. 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]. Anti-erythroid antibodies are the classical marks of serologic and hemolytic transfusion reactions. Reduced haptoglobin levels usually occur in both types of haemolysis. It is defined as the immunological destruction of red blood cells by antibodies whose specificity corresponds to antigens found on other cells/blood cells (e.g. 5 0 obj 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 Its based on principles of collaboration, unobstructed discovery, and, most importantly, scientific progression. In a situation in which, despite activation of the complement system, through antigen-antibody reaction, there is no intravascular haemolysis, red blood cells with detectable C3b component remain in the circulation. Acute HA can occur during and immediately after graft infusion as a consequence of donor's RBC hemolysis. Finally, disease relapse needs to be considered and ruled out. Acute haemolytic transfusion reactions are most often the result of clerical error. The blood unit should be checked at the patients bedside, whether it was properly administered. Diagnosis and treatment of transplantation-associated thrombotic microangiopathy: real progress or are we still waiting? 0000002721 00000 n TNF- also stimulates endothelial cells to synthesise adhesion molecules and chemotactic cytokines [22]. stream Matthew Yan, Christine Cserti-Gazdewich; Inpatient Non-Hemolytic Delayed Serologic Transfusion Reactions and Hospital Length of Stay: Is There an Association?. Delayed red cell engraftment due to host anti-donor isohemagglutinins may occur. Compared with non-anti-RBC and other anti-RBC transfusion reactions, NH-DSTRs were significantly less frequently classified as severe (Table 1). No cases of acute haemolytic reaction caused by anti-Lua antibodies have been reported, delayed transfusion haemolytic reaction is rare and occurs only in mild form. Someone with more knowledge please free to jump in and add/correct. 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. Autoimmune hemolytic anemia. /CreationDate (D:20161012131918-04'00') Webhemolytic transfusion reaction: Transfusion medicine A therapy-related event mediated by 2 different mechanisms: 1. The number of reported cases of delayed haemolytic transfusion reaction was higher than in 2016, but comparable with previous years [6]. Minor ABO-incompatible HSCT is characterized by the transfer of donor isohemagglutinins directed against the recipient's RBC antigens. In general, switching to another calcineurin inhibitor or sirolimus is not recommended. In unconscious patients and patients under general anaesthesia, it may be difficult to recognise a haemolytic transfusion reaction, as some symptoms may go unnoticed (e.g. Therefore, prior to conducting laboratory tests of donor blood, bacteriological examination of the component remaining after the transfusion cessation should be conducted. 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. 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. In the case of minor incompatibility both immediate and delayed hemolysis can occur.21 In this case, management is similar to ABO-incompatibility. 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. There was no significant difference between groups when evaluating inpatient mortality. 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). AB plasma is the universal donor source. The most common cause is immunological incompatibility between a donor and a blood recipient. One of them was the use of improved techniques for detecting clinically relevant alloantibodies, which reduce the number of haemolytic transfusion reactions observed in blood recipients. found that, using current laboratory methods, 25% of red blood cell antibodies become indeterminate on average after about 10months from production [43]. Febrile nonhemolytic transfusion reactions (FNHTRs) are common, occurring with 13% of transfusions. The nature of the reaction may not be immediately apparent, In those with concurrent hemolysis, the red blood cell (RBC) breakdown may be severe enough to command supportive care. Hemoglobin monitoring (sometimes repetitively in 1 day in case of severe hemolysis), a full blood count including reticulocytes, blood smear (schistocytes? By making research easy to access, and puts the academic needs of the researchers before the business interests of publishers. *1 J "6DTpDQ2(C"QDqpIdy~kg} LX Xg` l pBF|l *? Y"1 P\8=W%O4M0J"Y2Vs,[|e92se'9`2&ctI@o|N6 (.sSdl-c(2-y H_/XZ.$&\SM07#1Yr fYym";8980m-m(]v^DW~ emi ]P`/ u}q|^R,g+\Kk)/C_|Rax8t1C^7nfzDpu$/EDL L[B@X! How do I approach ABO-incompatible hematopoietic progenitor cell transplantation? Hemolysis can be severe, even fatal, and persists until all the recipient RBCs are replaced by transfused or donor-derived RBCs. They activate the complement system to the stage of binding of the C3b component, causing extravascular haemolysis. 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. Massive immune haemolysis after allogeneic peripheral blood stem cell transplantation with minor ABO incompatibility, Transfusion policy in ABO-incompatible allogeneic stem cell transplantation, Immune hemolysis involving non-ABO/RhD alloantibodies following hematopoietic stem cell transplantation, Non-ABO red blood cell alloantibodies following allogeneic hematopoietic stem cell transplantation, ABO incompatibility as an adverse risk factor for survival after allogeneic bone marrow transplantation, ABO-incompatible bone marrow transplantation: the transfusion of incompatible plasma may exacerbate regimen-related toxicity, Adverse effects of immunoglobulin G therapy: thromboembolism and haemolysis, Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation, Validation of recently proposed consensus criteria for thrombotic microangiopathy after allogeneic hematopoietic stem-cell transplantation, Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. 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. In comparison extravascular haemolysis is called delayed haemolytic transfusion reaction and usually occurs 24h or days after the end of the transfusion. /Creator (Apache FOP Version 1.0) It enforces the introduction of procedures eliminating further errors. Flow cytometry proved to be a similarly sensitive method. Unfortunately, despite many studies, it has not been possible to determine the critical titre of anti-A and/or anti-B antibodies that would be safe in the event of transfusion of ABO incompatible platelet concentrates, and in many countries, proprietary haemolysis prevention programs have been developed for recipients of incompatible platelets [48, 49, 50, 53]. 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. For any urgent enquiries please contact our customer services team who are ready to help with any problems. 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]. Red blood cell transfusion can also stimulate the production of alloantibodies without the occurrence of haemolysis. In general, intravascular haemolysis is called as an early acute haemolytic transfusion reaction. Table 9 summarises the treatment options used in haemolytic transfusion reactions. %%EOF Transfusion of plasma, platelet or granulocyte concentrate from donors incompatible in the ABO system with the recipient may lead to acute haemolytic transfusion reaction and even death. In case of immune-mediated hemolysis, a direct antiglobulin test (DAT), elution (also against a non-O RBC panel in case of ABO incompatibility), isohemagglutinin titration, and absorption techniques are required. The most common reaction among the acute (approximately 30%) was haemolysis resulting from ABO incompatibility [5]. Splenectomy can be recommended to patients without contraindications. 0000001175 00000 n Although infrequent, non-immune transfusion reactions, including haemolysis, transfusion-associated sepsis, and circulatory overload, should be considered in the differential diagnosis. The occurrence and severity of individual clinical symptoms can vary widely and are often non-specific [1, 8]. As long as PRCA persists (usually weeks to months until the isohemagglutinins have been adsorbed), transfusion requirements are high with consequent iron overload and potentially negative impact on overall survival.16 Management of post-transplant PRCA may include (besides transfusions) rituximab, anti-thymocyte globulin, TPE or immunoadsorption, decrease/discontinuation of immunosuppression, and donor lymphocyte infusions.8 Although plausible from a pathophysiologic point of view, none of these practices have been proven to be effective. Membrane inhibitor of reactive lysis (MIRL) (CD59) and decay accelerating factor (DAF) (CD55) are essential to protect red blood cells from haemolysis. 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. Hemolytic anemia (HA) is a condition in which the patient's red blood cells (RBCs) are prematurely destroyed. NH-DSTRs are associated with a longer LOS when compared with all other TRs. 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. Low concentration cytokines include IL-1, IL-6 and TNF-. The underlying disease, drugs (particularly those used for conditioning and immunosuppressants), infections, graft-versus-host disease, and autoimmune diseases may all contribute to the clinical and laboratory picture of HA. Usually, plasma alloantibodies are detectable at 47days after the transfusion and reach maximum activity between 10 and 15days after the transfusion. 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. Brief introduction to this section that descibes Open Access especially from an IntechOpen perspective, Want to get in touch? Additional fluid and diuretic therapy are usually not necessary. Positive DAT with anti-IgG and anti-C3d reagents may persist for several months [9]. Thus, clinical relevant and serious acute hemolytic reactions immediately after graft infusion are rare. Hemolytic anemia conditions encountered before, during and after hematopoietic stem cell transplantation (HSCT). Other causes of HA should be excluded. 0000002464 00000 n 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]. Basic Science and Clinical Practice in Blood Transfusion: Poster II, https://doi.org/10.1182/blood.V128.22.2633.2633, transfusion associated circulatory overload. 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. Antibodies of the IgM and IgG class (outside the IgG4 subclass) bind the C1q protein in the initial stage of activation. * Conditions that can occur alone or in combination in HSCT recipients. The specificity of the antibodies potentially responsible for intravascular and extravascular haemolysis is shown in Table 4. Laboratory tests show anaemia, increased LDH and bilirubin, decreased haptoglobin and higher white blood cell counts in post-transfusion haemolytic reactions. Hemolytic conditions in allogeneic hematopoietic stem cell transplant recipients. All rights reserved. pain and nausea). 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. All other drugs have to be critically reviewed and withdrawn if appropriate. 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 Princes Gate Court, Blood clots that form in the renal arterioles cause cortical kidney attacks. The incidence of autoantibodies after DHTR may be even higher because autoantibodies may mimic the specificity of alloantibodies. These diseases may relapse and thus HA can be a possible clinical manifestation either of relapse or of graft failure. DAF regulates C3a-converting activity. << Only in rare cases, platelet components have to be washed. *All RBC concentrates should be -irradiated (25-30 Gy) and leukocyte reduced. The three main types of immune hemolytic anemia are autoimmune, alloimmune, and drug-induced. 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. No relevant conflicts of interest to declare. Sickle cell disease (NORD) Hereditary spherocytosis. HA in general is either inherited or acquired, intravascular or extravascular, and immune or nonimmune mediated. Clinically significant differences between the above mechanisms of red blood cells destruction are based on the time of onset of haemolysis and the destruction rate of red blood cells. 40 0 obj<>stream 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). Number of antigenic determinants on the cell surface of the red blood cell (according to [12, 13]). WebFebrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reaction. 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. Drop in blood pressure is much more common in patients with intravascular than extravascular haemolysis. CXCL8 and CCL2 produced in the blood during ABO incompatibility will appear later than TNF- in very high concentrations. @~ (* {d+}G}WL$cGD2QZ4 E@@ A(q`1D `'u46ptc48.`R0) Elevated unbound bilirubin, LDH and decreased haptoglobin are observed. Bilirubin concentration depends on the severity of haemolysis and liver function. 38 14 The results of these studies indicate a critical role of monocyte activation in the development of intravascular haemolytic transfusion reaction [15]. 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]. 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. Your comment will be reviewed and published at the journal's discretion. In addition, due to immunosuppression, patients are at a risk of various infections, which in turn can cause HA or result in the development of post-transplant lymphoproliferative diseases; the latter, in rare cases, can manifest as AIHA.48. We can see youre on your way to BMJ Best Practice for, Do you want to go to BMJ Best Practice for, No, Id like to continue to BMJ Best Practice for, bleeding from mucous membranes, GI tract, or urinary tract, exfoliative dermatitis with mucocutaneous involvement, visual inspection of post-transfusion blood sample, repeat ABO testing on post-transfusion blood sample, Gram stain and culture of component and post-transfusion recipient samples. 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. Therefore, discussion of immune and nonimmune causes of hemolysis follows the chronological order of transplantation, and management of blood group incompatibility is discussed before transplantation-associated thrombotic microangiopathy (TA-TMA) and this before post-transplant AIHA. Lua antigens have uneven distribution on red blood cells and are weakly immunogenic. Additionally, differential diagnosis is not always obvious and patients can present with several potential risk factors for TMA (Table 4). PLS is more common in patients with blood group A, with a donor of group O, and cyclosporine A (CYA) alone as GVHD prophylaxis. In the population, delayed haemolytic transfusion reactions occur with a frequency of 1.69/100,000 per year [7]. Hematopoietic stem cell transplantation (HSCT) is unique because it is performed across the ABO blood group barrier. Currently, the incidence of haemolytic transfusion reactions is difficult to estimate. ?:0FBx$ !i@H[EE1PLV6QP>U(j {{{;}#tp8_\. >> The evaluation of haptoglobin and free hemoglobin in serum and urine can be helpful. Prospects through stem cell manipulation and graft processing have to be followed in the future. In case of relapse, isohemagglutinins produced from surviving recipient plasma cells can drive HA through destruction of donor RBCs. 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]. 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. However, transfusion requirement in acute AIHA can be a medical emergency and must not be delayed as RBC transfusions can be lifesaving. HA in general is either inherited or acquired, intravascular or extravascular, and immune or nonimmune mediated. Schonewille etal. 0000001590 00000 n 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. 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]. A test should be performed for the presence of antibodies in the recipient before and after the transfusion. WebGlucose-6-phosphate dehydrogenase (G6PD) deficiency. Alloantibody testing should be performed in the intermediate antiglobulin test (IAT) and enzyme test. @Rt CXCP%CBH@Rf[(t CQhz#0 Zl`O828.p|OX In the presence of schistocytes and thus the suspicion of microangiopathy, measurement of ADAMTS13 should be considered. Andreas Holbro, Division of Hematology, Department of Internal Medicine, University Hospital, Petersgraben 4, 4031 Basel, Switzerland; Phone: 0041-61-265-25-25; Fax: 0041-61-265-44-50; e-mail: andreas.holbro@usb.ch. Some symptoms of hemolytic anemia are the same as those for other forms of anemia. Therapeutic options in haemolytic transfusion reactions [1]. Unrelated donors in general have no history of transfusions; in related donors, where donor eligibility is less rigorous, careful transfusion and exposure history are important. Monitoring for clinical and laboratory signs of hemolysis is mandatory and in case of massive hemolysis frequent hemoglobin measurements should be performed.

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