 Abstract | | |
In many fields of clinical medicine and blood transfusion, the human leukocyte antigen (HLA) system is crucial. Alloimmunization happens as a result of an immune response to foreign antigens encountered during blood transfusion. This gives rise to alloantibodies against red blood cells (RBCs), HLA, or human platelet antigen (HPA). HLA alloimmunization following allogeneic transfusion was shown to be a result of contaminating white blood cells (WBCs) present in the product. It is a common complication of transfusion therapy that leads to difficulties in clinical intolerance and refractoriness to platelet transfusion during patient management. Single-donor platelets, prophylactic HLA matching, leukoreduction, and irradiation of cellular blood products are some of the mechanisms to prevent HLA alloimmunization during a blood transfusion. Now, the best approach to reduce the occurrence of primary HLA alloimmunization is the removal of WBCs from the blood by filtration. Keywords: Blood transfusion, human leukocyte antigen alloimmunization, human leukocyte antigen matching, leukoreduction, pathogen reduction, single-donor platelets, ultraviolet irradiation
How to cite this URL:
Adane T, Enawgaw B. Human leukocyte antigen alloimmunization prevention mechanisms in blood transfusion. Asian J Transfus Sci [Epub ahead of print] [cited 2023 Mar 24]. Available from: https://www.ajts.org/preprintarticle.asp?id=356860 |
| Introduction | |  |
The human leukocyte antigen (HLA) system is a cluster of gene complex encoding the major histocompatibility complex (MHC) proteins located on the cell membrane of white blood cells (WBCs) in humans from which its name was derived.[1] The HLA system is controlled by genes on the short arm of chromosome 6. The HLA loci are part of the genetic region known as the MHC. The MHC has genes (including HLA) that are integral to the normal function of the immune response. The essential role of the HLA antigens lies in the control of self-recognition and defense against microorganisms.[2] Based on structure and function, HLA is categorized into three groups: classes I, II, and III.[3] HLA Class I antigens are expressed on the surface of most nucleated cells of the body including platelets and red blood cells (RBCs). HLA Class II molecules are expressed in B-lymphocytes, antigen-presenting cells (APCs), and activated T-lymphocytes.[2],[4] The structure and function of HLA Class III molecules are poorly defined. Their gene cluster is present between Class I and Class II molecules and encodes important molecules involved in inflammatory processes.[3]
Alloimmunization occurs as a result of an immune response after exposure to foreign antigens during blood transfusion, pregnancy, or tissue transplant. This gives rise to alloantibodies against RBCs, HLA, or human platelet antigen (HPA).[5] Blood recipients become alloimmunized to HLA on WBC and platelets, which can limit subsequent transfusion of these cellular products.[6] HLA immunization is a common complication of transfusion therapy that leads to clinical intolerance and refractoriness to platelet transfusion.[7],[8] HLA alloimmunization also causes Febrile nonhemolytic transfusion reactions (FNHTRs), immunological platelet refractoriness, transfusion-related acute lung injury, and transfusion-associated graft-versus-host disease (TA-GVHD).[9]
The main mechanism for alloimmunization involves the presentation of the donor antigen peptides by APCs to the T-cell receptor on recipient CD4+ T-cells. Presentation of alloantigens may involve two distinct routes, the direct and indirect pathway of allorecognition. These were first defined by Lechler and Batchelor.[10] In direct recognition, the donor Class II HLA antigens expressed on donor APCs are directly recognized by recipient CD4 T-cells.[11] This occurs mainly for foreign HLA antigens.[12] Since mature RBCs lack HLA Class II antigens, direct antigen presentation will not occur in these cells. The interaction of donor APCs with T-cells in the host may afford a route to the development of antibodies by host B-cells against these donor antigens. The second route for antigen presentation is indirect allorecognition. It needs uptake and processing of donor cell fragments by host APCs.[13]
| Mechanisms for Prevention of Human Leukocyte Antigen Alloimmunization | | |
The awareness that leukocytes are the major cause of HLA sensitization fostered the development of methods which either inactivated HLA bearing cells by ultraviolet B irradiation or which reduc ed the leukocytes in red cell concentrates and in platelets.[14] An additional method to further minimize the probability of HLA alloimmunization is to use platelet collected from single donors, prophylactic HLA matching, and pathogen inactivation of blood products.[15],[16] Leukoreduction (LR) has been considered as a protective intervention for TA-GVHD. However, TA-GVHD continues to be reported within the era of LR. The major technology for preventing TA-GVHD is irradiation of blood components to inactivate residual lymphocytes.[17] Currently, LR and/or irradiation are used to prevent TA-GVHD.[18] Filtration and irradiation brought a series of clinical benefit, such as preventing or delaying the FNHTR, reducing the risk of leukocyte-associated virus transmission, inhibition of cytokine generation, complement activation, and preventing TA-GVHD.[19] A study conducted by Nelson et al. on transfusion-related immunomodulation showed that LR decreased HLA alloantibody production in naïve recipients but did not reduce the immunosuppressive effects of transfusion. Meanwhile, LR irradiated blood reduces immunosuppression.[20]
| Leukocyte-Poor Packed Red Blood Cells and Platelet Concentrates | | |
LR is the reduction of WBC concentration in blood components, namely RBC concentrates, platelet concentrates (PCs), and plasma obtained from the fractionation of whole blood or apheresis. It has been estimated that the average content of WBCs in donated human whole blood is 109/unit. By the current standards, the total WBC content in a blood unit should be <5 × 106/unit after preparation and a minimum of 85% of whole blood or RBCs is retained.[21] LR reduces but does not entirely remove donor WBCs from blood products. Residual WBCs passed from donor to recipient have the capacity to induce complications in the recipient.[13]
Different methods are available to remove WBCs from the blood component. The methods include centrifugation, with or without cell washing, and blood filtration technology.[22] Centrifugation with buffy coat removal and/or automated cell washing is relatively inefficient, removing at best 1–2 logs of WBCs (90%–99%). However, this percentage of removal leaves 7–8 logs of WBCs in the RBC unit, a number which is probably sufficient to stimulate HLA antibody formation. Currently, the process of LR is performed using selective LR filters, which enable <1 × 106 residual WBCs to be obtained in a RBC or PC unit.[8] The first filters (first generation) had the capacity to hold approximately 1 log of WBCs. The second-generation filters arose encouraging holding of 3 logs with verified efficacy to prevent FNHTR.[23] These are 40 mm filters designed to remove microaggregates of fibrin, platelets, and WBCs from RBC concentrates.[24] Newly designed filters (third and fourth generation) are capable of removing up to 3 logs (99.9%) of contaminated WBCs.[25] They have pores ranging from 5 to 50 mm and are able to meet current hemocomponents' quality standards.[26]
The WBC removal filters contain multiple layers of synthetic polyester nonwoven fibers that selectively retain WBCs while allowing RBCs and/or platelets to flow through. Lymphocytes and monocytes are passively held in the filter, while granulocytes are trapped by adhesion. These filters are highly effective, easy to handle, and do not require transient inactivation of platelets before filtration. It has therefore emerged as an effective and reliable way for LR.[21],[27],[28] They can be used to perform leukodepletion before storage (online leukodepletion) or in the laboratory (prestorage), or it may even be carried out at the bedside during blood transfusion.[29],[30]
Formation of antibodies against histocompatibility antigens occurs if platelets are contaminated with WBCs. Platelets are only capable of inducing a secondary immune response. The induction of a primary immune response is dependent on the presentation of foreign Class I antigens by transfused WBCs. It intimates that alloimmunization against Class I antigens can be prevented by leucodepletion of PC.[12],[31] The current concept suggests that antigens on the platelets by themselves are not capable of initiating a primary immune response. However, even with their weaker antigenic capability, they can propagate a secondary immune response. Therefore, to avoid primary alloimmunization against the histocompatibility antigens, the total content of WBCs in a unit of RBCs should be less than the specified standard. The storage time plays a critical role in RBC transfusion. Although fresh donated RBCs seem to induce HLA alloimmunization, RBCs stored for at least 15 days pretend to induce immune tolerance against foreign HLA antigens.[25] For PCs derived from whole blood, the standard requires that each unit contains no more than 0.83 × 105 WBC per unit. Currently, the removal of WBCs from PCs by filtration (using third and fourth generation) is the best approach to reduce the incidence of primary HLA alloimmunization.[12],[32]
LR of RBCs and platelets has been shown to decrease the incidence of HLA alloantibody formation in transfusion recipients. This is of primary importance in patients who require ongoing platelet transfusion support, as anti-HLA antibodies can lead to platelet refractoriness by binding to the corresponding antigens (major histocompatibility complex) on transfused platelets.[33] After multiple transfusions, up to 20% of recipients became refractory because of an immune cause (alloantibodies against HLA Class I antigens). The use of leukocyte-depleted platelets had decreased the incidence of the alloimmune refractoriness to 5% or less.[34]
Introduction of universal LR in most high-income countries has resulted in a reduction of alloimmunization from 19%–45% to 9%–18%, and concomitant alloimmune refractoriness from 14% to 4%.[35],[36] Universal prestorage LR was introduced in Canada in the late 1990s. A subsequent randomized controlled trial by Seftel et al. showed that following implementation of LR policy, there was a significant reduction in both the incidence of alloimmunization (19% vs. 7%) and alloimmune refractoriness (14% vs. 4%) in chronically transfused hematological patients.[36] Another study conducted by Murphy et al. showed that the benefit of leukocyte depletion of blood components in reducing HLA alloimmunization was confirmed, with only 16% of patients developing lymphocytotoxic antibodies, as compared with 48% of patients in a control group receiving standard (nonleukocyte depleted) blood components.[37]
A study on platelet refractoriness and alloimmunization demonstrated that the routine use of leukocyte-depleted PC reduces the incidence of HLA alloimmunization in the general population from 70% to approximately 25%, and the frequency of alloimmune refractoriness from 15% to 5% among patients receiving chemotherapy when WBCs are removed or inactivated.[35]
Quality control to ensure adequate LR can be carried out by measuring WBC counts on every concentrate prior to release for transfusion, but this is labor intensive. It is equally acceptable to use statistical process control to ensure that the LR procedure remains within predetermined limits set after initial validation of each filter or other technologies.[38] Methods used to count residual WBCs are flow cytometry and large-volume microscopic chambers.[39] The following parameters should be assessed to assure an overall statistically based level of blood product conformance [Table 1]. | Table 1: Currently accepted standards for leukoreduction blood components
Click here to view |
| Ultraviolet-B Irradiation | | |
Another type of technology that prevents or delays the appearance of HLA alloimmunization in transfused patients is the use of UV-B radiation. Rather than removing Class II antigen-containing WBCs as filters, UV-B irradiation appears to inactivate Class II molecules present in donor APCs, thereby inhibiting recipient recognition of transfused donor cells as foreign. This UV-B irradiation process is sufficient for the inactivation of WBCs in PC units.
Since hemoglobin (Hgb) absorbs light in the UV-B spectral range, effective UV-B irradiation of the WBCs present in full units of RBC products cannot be achieved with existing technology. The UV-B cannot penetrate farther than a few mm into the RBCs, therefore, most of the unit fails to receive any radiation. To radiate whole blood effectively, a thin layer of blood is needed, and the cross-sectional diameter of the layer of blood to be irradiated should not exceed several mm. Thus, for full units of whole blood or RBC products, third-generation filters still must be used to remove the WBCs physically.[40]
The correct mechanism of UV-B inactivation is unclear. However, it relates to interference with movement of calcium in the cell membrane.[41] Initially, it had been thought that the protective effect was related to the loss or shedding of Class II antigens from the donor APC induced by the UV-B irradiation. This concept has been challenged by others and definitive studies are lacking. Recent work implicates there is loss of intracellular adhesion molecule 1 (ICAM-1) from the surface of APC monocytes following UV-B irradiation. The ICAM-1 is an accessory adhesive molecule involved in stabilization of the donor APC and recipient T-cell complex.[42]
UV-B illumination in vitro affected not only the ability of WBCs to produce cytokines but also their expression of adhesion and costimulatory molecules, which are essential for cell-to-cell communication and T-cell activation. UV-B-illuminated WBCs did not induce allogeneic T-cell proliferation in vitro.[43] UV radiation abrogates the ability of APCs to stimulate responder T-cells in the mixed lymphocyte reaction, and this inactivation is believed to prevent the induction of anti-HLA antibodies in vivo.[44] There is some evidence that UV-B irradiation of platelets prior to infusion reduces the development of alloantibodies and improves platelet count increments in lymphocytotoxic antibody-positive patients.[13]
The relatively high dose of UV-B used to inactivate WBCs in PCs may induce fragmentation of cells and alloimmunization according to the indirect pathway of allorecognition. Fragmentation of cells is associated with exposure to a wide range of UV-B energy, along with the wide distribution of UV-B-induced DNA damage.[44]
Lymphocytes can be rendered nonviable by exposure to irradiation. Irradiation at doses specified in the standards does not cause significant harm to other blood cells. Thus, an irradiated component can be administered safely to all the patients. However, the in vitro quality of irradiated RBCs deteriorates more rapidly during storage than the quality of nonirradiated red cell components. Therefore, irradiation reduces the shelf-life of RBC components.[45] UV-B irradiation techniques are useless in transfusion practice, and filtration remains a practical and effective means of reducing HLA immunization in humans.[7] The effects of radiation are most significant on RBC products and include an increase in extracellular potassium and a decreased survival of RBCs after transfusion. The in vivo viability of irradiated RBCs, evaluated after 2 h of recovery, is reduced by 3%–10% compared to nonirradiated RBCs. Irradiation also induces damage to the RBC membrane.[33] Another problem with UV-B radiation is the possibility of storage on PC. Platelets can be well stored for 5 days after UV-B irradiation at a low dose. At a higher dose, when platelets were stored for 4 days after UV-B irradiation, significant changes in platelet storage properties were observed.[40]
| Pathogen Reduction Technology | | |
The introduction of pathogen inactivation techniques increases the availability of UV illumination. Now, three systems have been introduced to improve the safety of blood transfusions; INTERCEPT, Theraflex (MacoPharma), and Mirasol. Although the illumination wavelengths differ and a photochemical agent may be added to induce DNA damage in the pathogens, all the techniques use UV light to induce DNA and/or RNA damage for pathogen inactivation.[46] The use of pathogen reduction technology (PRT) may not only provide a means to decrease or eliminate disease transmission via pathogens in blood but may also afford a means to eliminate complications due to residual donor WBCs that contaminate blood products.[13] Pathogen inactivation techniques provide safe transfusions by reducing infectious disease transmission and inactivating contaminating WBCs by providing pathogen-reduced blood components.[47]
INTERCEPT uses a synthetic psoralen compound, amotosalen, and UV-A light to prevent nucleic acid replication, thereby inactivating infectious agents and lymphocytes. Following INTERCEPT treatment, an adsorption step removes nearly all residual amotosalen.[48] Amotosalen penetrates the cellular membrane forming noncovalent links between pyrimidine residues in DNA and RNA. The UV illumination induces a photochemical reaction that transforms the preexisting link into an irreversible covalent bond, preventing DNA replication and RNA transcription.[49]
The THERAFLEX system uses UVC light in combination with strong agitation which facilitates light penetration and does not require a photosensitizer. UVC acts directly on nucleic acids to induce pyrimidine dimers to block DNA replication.[50] This technology is currently under evaluation in a Phase III clinical trial in Europe.[48]
The Mirasol pathogen inactivation process involves the addition of riboflavin (Vitamin B2) to the blood component, followed by UV-A and UV-B illumination. Riboflavin binds to nucleic acids, and after exposure to UV light, the activated nucleic acid bound riboflavin molecules react with nucleic acid bases, impairing cell replication.[51] Riboflavin associates with nucleic acids and mediates an oxygen-independent electron transfer process leading to the modification of nucleic acids, primarily on guanine residues, and the conversion of riboflavin to its photoproduct lumichrome.[52] The Mirasol system is capable of inactivating significant levels of pathogens and WBCs and is thus expected to reduce the risk of disease transmission and adverse events while maintaining acceptable quality of the treated blood products.[53] Mirasol-treated mononuclear cells were unable to induce proliferation of allogeneic responder peripheral blood mononuclear cells, suggesting that Mirasol treatment inhibited antigen presentation capabilities in the treated cells. This is different from isolated UV-B irradiation alone, which has been shown to prevent proliferation but leaves antigen presentation unaffected.[54] Compared to the use of UV light alone, which causes reversible nucleic acid damage, damage induced by riboflavin is irreversible since replication and repair processes are impaired due to the guanine base modification.[55]
A study conducted by Jackman et al. on understanding the loss of donor WBC immunogenicity after pathogen reduction showed that Mirasol-treated APCs have a markedly reduced survival, reduced surface expression of Class II HLA and costimulatory molecules, and defective cell-to-cell conjugation, and fail to effectively stimulate allogeneic cells. They also lose the capability of synthesizing new cytokines.[56] Recently introduced pathogen-inactivation techniques have been hypothesized to further reduce the risk of alloimmunization.[57] In contrast, in the recently published Pathogen Reduction Evaluation and Predictive Analytical Rating Score study, pathogen inactivation seemed not effective in protecting HLA Class I alloimmunization in humans.[35]
A prospective randomized multicenter trial study conducted by Saris et al. concluded that Mirasol pathogen inactivation does not prevent HLA Class I or II alloimmunization after platelet transfusions. According to this study, even though pathogen inactivation may improve blood transfusion safety, it did not protect against the formation of HLA Class I or II antibodies. The observed increase in HLA Class I alloimmunization by pathogen-reduced PCs is likely caused by a platelet-mediated indirect immunization pathway, possibly involving the enhanced development of platelet storage lesions after pathogen inactivation.[43]
During PRT technology, there is an increase in HLA Class I antibodies but a contradictory protection from HLA Class II alloimmunization with Mirasol treatment. Although WBCs express both HLA Class I and II, platelets express only Class I antigens. Accordingly, there is a speculation that PRT could protect from WBC alloimmunization, but platelets, which express only HLA Class I, could escape this protective effect. The treatment of RBCs or whole blood has been more challenging due to the absorption of light by Hgb. Although the peak absorption of Hgb (400–450 nm) is outside the spectral region of the Mirasol lamp output, the UV light energy dose delivered to units of whole blood is normalized for RBC volume. Generally, the effects of pathogen inactivation techniques on alloimmunization rates are incompletely understood.[16]
Disadvantages of PRT – the techniques could cause damage to the components, which could reduce the in vivo shelf life of RBCs or platelets, or reduce clotting proteins in fresh frozen plasma. Toxicities remain a concern.[58] Although PRTs are convenient to reduce the risk of transfusion-transmitted infections, they can affect platelets and derived microparticles properties and, thus, impact their functions.[59] Currently available PRTs, which have been validated for pathogen inactivation, are intended exclusively for use in plasma and platelets, while the PRTs for whole blood are still in the clinical trial phase. PRTs also have limitations related to their proven ineffectiveness against some pathogens and increased storage lesions.[60]
| Prophylactic Human Leukocyte Antigen-Matched Blood | | |
The most common cause of platelet refractoriness is the presence of HLA antibodies and it can be confirmed by detecting HLA antibodies.[61] Searching a compatible platelet unit for an alloimmunized patient depends on the available tests, the frequency of the patient's HLA type relative to the pool of HLA compatible donors, and the level of alloimmunization.[62] For patients with platelet refractoriness due to HLA alloimmunization, two main transfusion approaches are currently used: transfusion with crossed-match platelets or transfusion with HLA-compatible platelets.[63] Other alternative measures with varying degrees of efficacy include high-dose ABO-compatible platelet transfusion, intravenous gamma globulin, and plasmapheresis. Recently, the transfusion of platelets treated with specific acid dilutions to an alloimmunized patient had encouraging results.[64]
| Cross-Matched Platelets | | |
The cross-match approach is widely used because compatible units are usually available within 24 h, and both HLA and HPA compatibility issues are addressed without further testing.[65] Cross-match-compatible platelets are readily available, less expensive, and allow matching for platelet-specific antigens.[66] Platelet cross-matching assays are a rapid alternative to the HLA-matched approach to the management of platelet refractoriness.[67] The assays have been used for the identification of candidate platelet donors and may be beneficial for patients in whom refractoriness is due to HPA alloimmunization, thus HLA-compatible platelet transfusion is of no value.[68] In severely alloimmunized patients, this is quite problematic, which can make it difficult to find enough compatible unit.[65]
Ideally, ABO-identical platelet transfusions should be transfused, however, ABO nonidentical transfusions can be given if ABO-matched platelets are not available. Transfusion of ABO mismatched platelet leads to platelet refractoriness early during transfusion. Hemolysis due to anti-A and anti-B antibodies in the plasma of mismatched ABO platelet transfusions has also been reported.[69] A study conducted by Carr et al. evaluated 26 oncohematology patients who had not previously been transfused with blood platelets. In a first group, 13 patients were transfused with platelets from their ABO group, and in a second group, 13 patients received platelets with a large ABO mismatch. Nine patients who received ABO incompatible platelets showed refractoriness to platelet transfusion, whereas only one patient developed with ABO compatible platelets.[70]
A variety of methods have been used for platelet cross-matching. Enzyme-linked immunosorbent assay, flow cytometry, platelet immunofluorescence, and a solid phase red cell adherence (SPRCA) assay were the most widely used techniques. Platelet cross-match transfusion practice is primarily performed by SPRCA test.[63] In this assay, various donor platelets are mixed with the patient's serum. Antibodies to HLA or HPA that bind to platelets are visualized with indicator RBCs coated with anti-immunoglobulin G.[65]
| Human Leukocyte Antigen Matched Platelets | | |
Platelet or lymphocyte cross-matching techniques can be used to confirm the eligibility of an individual donor, but the frequency with which a single individual can provide platelets is limited. An alternative source is the HLA phenotype from a potential volunteer platelet bank for use in appropriate patients. The disadvantage of this approach is that the polymorphism of each of the HLA Class I allele systems results in little chance of finding HLA-compatible donors. Therefore, voluntary banks have to be large to have any chance of success. HLA matching can be done by searching for donors bearing the identical HLA-A and HLA-B antigens as the platelet recipients. An alternative strategy is to specify the HLA antibodies of the platelet recipient and to search for donors not bearing a corresponding HLA antigen. The latter strategy is able to identify much better-suited donors than the former.[71],[72]
HLA-specific antibody sensitization can be minimized and/or prevented by administration of HLA-selected units. The HLA matchmaker is based on the principle that every HLA molecule possesses a distinct array of polymorphic triplets and those that are present on antibody accessible portions of the molecule are immunogenic. Patients will not produce HLA-specific antibodies against self-antigenic epitopes but will form alloantibodies to HLA epitopes, which are foreign. By comparing the similarity between the HLA molecules of a potential donor and recipient, it is possible to determine how many immunogenic triplets that patient will encounter.[73] The algorithm assesses donor-recipient compatibility through intralocus and interlocus comparisons and determines what triplets in antibody-accessible positions on mismatched HLA molecules are different or shared between donor and patient.[74] There is marked reduction in the incidence of HLA antibodies in HLA-matched groups. The routine use of HLA-matched platelet donors would require facilities for plateletpheresis which are not available in all centers.[37] The method is also expensive and time consuming.[63] A study conducted by Pavenski et al. showed that HLA-matched platelets did not reduce alloimmunization and refractoriness rates beyond that offered by LR. HLA-matched platelets led to better count increments and percentage of platelet recovery in refractory patients1 h after transfusion.[75]
| Single-Donor Platelets | | |
Two types of PCs are available for transfusion; Random donor platelet (RDP) and Single-donor platelets (SDP). A SDP concentrate is prepared from a single donor with the help of an automated cell separator and contains approximately 3 × 1011 platelet suspended in 200–400 ml of plasma. It is expected to raise the platelet count by 30,000–60,000/μl. Platelets collected by apheresis are usually WBCs depleted. A single unit of apheresis platelets is equivalent to 4–6 units of RDP units.[76]
RDP is prepared from units of whole blood collected from random donors and contains at least 5.5 × 1010 platelets suspended in 40–70 ml of plasma.[77] It contains approximately 7 × 1010 platelets and increases the platelet count by 5000–10,000/μl in an average-sized adult.[78]
The use of SDP is preferred over RDP due to the following reasons. It is important in reduction of infectious complications and transfusion reactions, ease of leucodepletion, reduction in transfusion frequency, prevention of alloimmunization, treatment of alloimmunized recipients, enhancement of platelet quality, and elimination of the need to pool whole blood-derived platelets in transfusion service.[79] The most substantial advantage of SDP was the reduction of septic platelet transfusion reactions (SPTR) from bacterial contamination in stored platelets. Unfortunately, SDPs do not eliminate all SPTRs, which persist at a rate of 1 in 15,000 transfusion events with the exclusive use of SDPs.[80] Until more specific means to eliminate SPTR are developed, SDPs are a useful means of limiting their occurrence in transfused patients.[81]
SDP is also important for shielding the patients from multiple immunological allogenic exposures.[78] Besides, SDP prepared with the use of platelet additive solutions would seem to be less likely to provoke allergic transfusion reactions, but convincing evidence of the superiority of SDP is not abundant.[82] With some types of current apheresis technology, the number of WBCs in a SDP averages at least a log less than the number of WBCs in the equivalent pool of RDP. SDP transfusion still has an important advantage in bleeding prophylaxis during therapy for hematologic malignancies.[83]
However, recent evidence suggests that SDP may be associated with a higher rate of adverse reactions than RDP. Although transfusions with apheresis platelets may reduce exposure to different donors, apheresis platelets from an HLA-matched donor or a blood relative may increase the risk of TA-GVHD.[84] Currently, there is debate about which platelet product should be used. Largely because of the lower cost, many transfusion centers favor PC, with SDP reserved for patients who require HLA-matched platelets. SDP outperform RDP in ease of LR, decreasing the risk of SPTR, treating alloimmunization, and increasing the transfusion interval. SDP should be the platelet therapy of choice for hematologic patients.[81]
| Conclusion | | |
The use of LR, UV-B illumination, pathogen inactivation, HLA matched blood, and SDPs were the mechanisms to prevent HLA alloimmunization. Although UV-B irradiation technique is important in the prevention of HLA alloimmunization, it has several limitations. PRT is also important to minimize Class IIalloimmunization, but it seemed not effective in prevention of Class I HLA alloimmunization. LR of RBCs and platelets has been shown to decrease the incidence of HLA alloantibody formation in transfusion recipients. Generally, evidence-based comparative study is needed to explore the effectiveness of various mechanisms for the prevention of HLA alloimmunization in blood transfusion.
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Conflicts of interest
There are no conflicts of interest.
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Correspondence Address:
Tiruneh Adane,
Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar
Ethiopia
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ajts.ajts_144_21
[Table 1] |
