Red blood cell transfusions are associated with HLA class I but not H‐Y alloantibodies in children with sickle cell disease

Blood transfusions can induce alloantibodies to antigens on red blood cells (RBCs), white blood cells and platelets, with these alloantibodies affecting transfusion and transplantation. While transfusion‐related alloimmunization against RBC antigens and human leucocyte antigens (HLA) have been studied, transfusion‐related alloimmunization to minor histocompatibility antigens (mHA), such as H‐Y antigens, has not been clinically characterized. We conducted a cross‐sectional study of 114 children with sickle cell disease (SCD) and tested for antibodies to 5 H‐Y antigens and to HLA class I and class II. Few patients had H‐Y antibodies, with no significant differences in the prevalence of any H‐Y antibody observed among transfused females (7%), transfused males (6%) and never transfused females (4%). In contrast, HLA class I, but not HLA class II, antibodies were more prevalent among transfused than never transfused patients (class I: 33% vs. 13%, P = 0·046; class II: 7% vs. 8%, P = 0·67). Among transfused patients, RBC alloantibody history but not amount of transfusion exposure was associated with a high (>25%) HLA class I panel reactive antibody (Odds ratio 6·8, 95% confidence interval 2·1–22·3). These results are consistent with immunological responder and non‐responder phenotypes, wherein a subset of patients with SCD may be at higher risk for transfusion‐related alloimmunization.     

Early occurrence of red blood cell alloimmunization in patients with sickle cell disease

Red blood cell (RBC) alloimmunization is a major complication of transfusion therapy in sickle cell disease (SCD). Identification of high‐risk patients is hampered by lack of studies that take the cumulative transfusion exposure into account. In this retrospective cohort study among previously non‐transfused SCD patients in the Netherlands, we aimed to elucidate the association between the cumulative transfusion exposure, first alloimmunization and independent risk factors. A total of 245 patients received 11 952 RBC units. Alloimmunization occurred in 43 patients (18%), half of them formed their first alloantibody before the 8th unit. In patients with exposure to non‐extended matched transfusions (ABO and RhD) the cumulative alloimmunization risk increased up to 35% after 60 transfused units. This was significantly higher compared to a general transfused population (HR 6.6, CI 4.2–10.6). Receiving the first transfusion after the age of 5 was an independent risk factor for alloimmunization (HR 2.3, CI 1.0–5.1). Incidental, episodic transfusions in comparison to chronic scheme transfusions (HR 2.3, CI 0.9–6.0), and exposure to non‐extended matched units in comparison to extended matching (HR 2.0, CI 0.9–4.6) seemed to confer a higher alloimmunization risk. The majority of first alloantibodies are formed after minor transfusion exposure, substantiating suggestions of a responder phenotype in SCD and stressing the need for risk factor identification. In this study, older age at first transfusion, episodic transfusions and non‐extended matched transfusions appeared to be risk factors for alloimmunization. Am. J. Hematol. 91:763–769, 2016. © 2017 Wiley Periodicals, Inc.     

Alloimmunization is associated with older age of transfused red blood cells in sickle cell disease

Red blood cell (RBC) alloimmunization is a significant clinical complication of sickle cell disease (SCD). It can lead to difficulty with cross‐matching for future transfusions and may sometimes trigger life‐threatening delayed hemolytic transfusion reactions. We conducted a retrospective study to explore the association of clinical complications and age of RBC with alloimmunization in patients with SCD followed at a single institution from 2005 to 2012. One hundred and sixty six patients with a total of 488 RBC transfusions were evaluated. Nineteen patients (11%) developed new alloantibodies following blood transfusions during the period of review. The median age of RBC units was 20 days (interquartile range: 14–27 days). RBC antibody formation was significantly associated with the age of RBC units (P = 0.002), with a hazard ratio of 3.5 (95% CI: 1.71–7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66–35.97) for a unit that was 35 days old, 28 days after the blood transfusion. No association was observed between RBC alloimmunization and acute vaso‐occlusive complications. Although increased echocardiography‐derived tricuspid regurgitant jet velocity (TRV) was associated with the presence of RBC alloantibodies (P = 0.02), TRV was not significantly associated with alloimmunization when adjusted for patient age and number of transfused RBC units. Our study suggests that RBC antibody formation is significantly associated with older age of RBCs at the time of transfusion. Prospective studies in patients with SCD are required to confirm this finding. Am. J. Hematol. 90:691–695, 2015. © 2015 Wiley Periodicals, Inc.     

Clinical aspects of platelet transfusions

Refractoriness is the most important complication of platelet transfusion therapy, occurring in about 50% of patients receiving repeated transfusions. The major causes are HLA alloimmunization and non-immune platelet consumption associated with clinical factors such as septicaemia. DIC and splenomegaly. Initial management of alloimmunized patients who are refractory to platelet transfusions from random donors is the use of HLA-matched platelet transfusions, which improve responses to transfusions in about 65% of patients. It may be difficult to provide effective platelet transfusion support for alloimmunized patients not responding to HLA-matched transfusions. There has been much interest in methods for the prevention of HLA alloimmunization. Primary HLA alloimmunization is dependent on the presence of HLA class II antigen-bearing cells in transfusions; pure platelet transfusions are non-immunogenic as platelets only express HLA class I antigens. The use of leucocyte-depleted blood components in multitransfused patients has resulted in a reduction in HLA alloimmunization and platelet refractioness. Improvements in the techniques for leucocyte-depletion of red cell and platelet concentrates and the possibility of inactivation of HLA class II antigen-bearing cells by UV irradiation makes prevention of alloimmunization an attainable goal.     

Bleeding risk and platelet transfusion refractoriness in patients with acute myelogenous leukemia who undergo autologous stem cell transplantation

Therapy for acute myelogenous leukemia can be complicated by alloimmunization to histocompatibility antigens (HLA), with resultant refractoriness to platelet transfusions. Autologous peripheral blood or bone marrow stem cell transplantation (referred here collectively as 'autoBMT') is emerging as a standard consolidative strategy in acute myelogenous leukemia (AML). We had noted life-threatening bleeding associated with platelet transfusion refractoriness following autoBMT; we therefore retrospectively analyzed 39 AML patients for this complication following BMT. All patients received high-dose chemoradiotherapy, followed by infusion of allogeneic sibling donor (n = 12, alloBMT) or autologous (n = 27, autoBMT) stem cells. HLA alloimmunization was assessed if patients were suspected of immune refractoriness to random donor platelet transfusions. Within 100 days of stem cell infusion, one of three alloBMT and six of 12 autoBMT recipients tested were HLA alloimmunized (not statistically significant, NS). Five of six HLA alloimmunized autoBMT patients experienced delayed bleeding, which contributed to their demise while still in remission (P < 0.001). Increased platelet requirements in HLA alloimmunized autoBMT recipients were observed between days 61 and 100 post-BMT, at a median of 211 platelet transfusions vs 0 in non-alloimmunized autoBMT patients (P < 0.01) and 17 in alloBMT patients. Our data suggest that platelet transfusion refractoriness, when associated with HLA alloimmunization, is a risk factor for increased platelet transfusion requirements, delayed bleeding, and poor outcome following autoBMT for AML.     

Platelet Alloimmunization after Transfusion

Background and objectives: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. Materials and methods: We studied the frequency of alloimmunization against platelet antigens in 117 patients who received a single series of blood transfusions. They received mostly saline-adenine-glucose + mannitol red blood cell components (poor in leukocytes and platelets) in connection with cardiac surgery. Platelet-specific antibodies were detected with the platelet ELISA and the monoclonal-antibody-specific immobilization of platelet antigen assay. HLA antibodies were detected by the standard lymphocyte cytotoxicity techniques. Results: We found platelet-specific anti-HPA-5b (anti-Br^a) in 2 cases (1.7%). One antibody was the result of de novo immunization. We detected lymphocytotoxic HLA antibodies in 21 patients (17.9%), of whom 18 (15.4%) had had no detectable antibodies before transfusion. There was a positive correlation between the transfused load of immunogenic materials and the frequency of alloimmunization against HLA antigens. In one third of the immunized patients, there was no history of previous immunization. Conclusion: There was a low incidence of platelet-specific antibodies after one series of blood transfusions in this group of patients. This is similar to the results of some previous studies in multiply transfused patients, but not with those of others who found a higher incidence.     

Use of leukocyte-depleted platelet concentrates for the prevention of refractoriness and primary HLA alloimmunization: a prospective, randomized trial

Compared with conventional transfusion regimes a strong reduction in HLA alloimmunization and refractoriness to platelet transfusions is obtained when both red blood cell concentrates (RBCs) and platelet concentrates (PCs) are depleted of leukocytes by filtration. Because most of the leukocyte contamination is introduced by transfusion of RBCs, filtration of RBCs appears rational, but uncertainty exists regarding the degree of leukocyte-depletion of PCs needed for the prevention of HLA alloimmunization and refractoriness. We conducted a prospective trial and randomized patients with acute leukemia to receive leukocyte-depleted PCs prepared either by centrifugation (mean leukocyte count 35 x 10(6)/PC of 6 U) or by filtration (mean leukocyte count less than 5 x 10(6)/PC of 6 U). Both groups received RBCs that were filtered after prior removal of the buffy coat. Clinical refractoriness occurred in 46% (12 of 26) of the evaluable patients that were transfused with centrifuged PCs and only in 11% (3 of 27) in the filtered group (P less than .005). De novo anti-HLA antibodies were detected in 42% (11 of 26) patients in the centrifuged group and only in 7% (2 of 27) of the patients receiving filtered PCs (P less than .004). In 8 of 11 alloimmunized patients in the centrifuged group antibodies were detected in the first 4 weeks of transfusion therapy while none of the patients in the filtered group became immunized against HLA antigens during that period. We conclude that for the prevention of HLA alloimmunization and refractoriness to platelet transfusions from random donors, both RBCs and PCs have to be leukocyte-depleted by filtration.     

Human leucocyte antigen alloimmunization after bone marrow transplantation: an association with chronic myelogenous leukaemia

Platelet refractoriness due to human leucocyte antigen (HLA) alloimmunization is a significant risk to allogeneic bone marrow transplant recipients. To identify factors contributing to this risk, we reviewed the records of 317 consecutive, paediatric, allogeneic bone marrow transplant recipients at a single institution. The 6-year estimated cumulative incidence of platelet refractoriness due to HLA alloimmunization was 2.6% +/- 0.9%. The incidence among patients with chronic myelogenous leukaemia (CML) 12.5% +/- 5.3% was significantly greater than that of other patients (1.1% +/- 0.6%, P < 0.001). Graft rejection (P = 0.003) and the number of platelet transfusions during the first 90 d after bone marrow transplantation (BMT) (P = 0.0025) were also significantly associated with alloimmunization. The association with CML and with graft rejection was not seen among patients alloimmunized before transplantation. Eight patients developed alloimmunization, of whom three had mismatched grafts and four had unrelated grafts. Alloantibody specificities, identified in seven patients, were unrelated to host or graft major histocompatibility complex (MHC). Host recognition of alloantigens in transfused blood products, not graft-host recognition, therefore seems predominantly responsible for the alloimmunization. These results show that paediatric CML patients have a significantly increased risk of platelet refractoriness due to HLA alloimmunization after BMT. Identifying the mechanism for the increased alloimmunization risk may assist in the development of therapies to prevent platelet refractoriness.     

Immunophenotypic parameters and RBC alloimmunization in children with sickle cell disease on chronic transfusion

Alloimmunization against red blood cell (RBC) antigens is a cause of morbidity and mortality in transfused patients with sickle cell disease (SCD). To investigate distinguishing characteristics of patients who develop RBC alloantibodies after transfusion (responders) versus those who do not (non‐responders), a cross‐sectional study of 90 children with SCD on chronic RBC transfusion therapy at a single institution was conducted in which 18 immune parameters (including T and B cell subsets) were tested via flow cytometry, and medical records were reviewed. RBC alloimmunization was present in 26/90 (29%) patients, with anti‐E, K, and C among the most commonly detected alloantibodies despite prophylactic matching for these antigens at the study institution. In addition, RBC autoantibodies had been detected in 18/26 (69%) of alloimmunized versus 7/64 (11%) of non‐alloimmunized patients (P < 0.0001). Alloimmunized patients were significantly older (median 13.0 years vs. 10.7 years, P = 0.010) and had more RBC unit exposures (median 148 U vs. 82 U, P = 0.020) than non‐alloimmunized patients. Sex, age at initiation of chronic transfusion, splenectomy, stroke, and transfusion outside of the study institution were not significantly associated with RBC alloimmunization. Alloimmunized patients had a significantly increased percentage of CD4+ T memory cells compared to non‐alloimmunized patients (57% vs. 49%, P = 0.0047), with no other significant differences in immune cell subsets or laboratory values detected between these groups. Additional research of RBC alloimmunization is needed to optimize transfusion therapy and to develop strategies to prevent alloimmunization. Am. J. Hematol. 90:1135–1141, 2015. © 2015 Wiley Periodicals, Inc.     

Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA-matched haematopoietic cell transplant for sickle cell disease

The relevance of donor-specific human leukocyte antigen (HLA) antibodies in HLA-mismatched haematopoietic cell transplant (HCT) is known, but the importance of HLA antibodies in HLA-matched HCT is unclear. We hypothesized that HLA antibodies detected before HCT would cause platelet transfusion refractoriness during HCT and investigated this in a multi-centre study. Pre-HCT samples from 45 paediatric patients with sickle cell disease (SCD) undergoing HLA-matched HCT were tested for HLA class I antibodies. The number of platelet transfusions received before day +45 was compared between those with and without antibodies. Thirteen of 45 (29%) patients had a positive HLA class I antibody screen, and these patients received significantly more platelet transfusions than patients without antibodies (median 19 vs. 7·5, P = 0·028). This platelet transfusion association remained significant when controlling for conditioning regimen. Among alloimmunized patients, there was no association between the panel-reactive antibody and the number of platelet transfusions. Patients with HLA class I antibodies also had a higher incidence of acute graft-versus-host disease (GVHD): 6/13 (46%) vs. 3/32 (9%), P = 0·011. Pre-HCT HLA class I alloimmunization is associated with increased platelet transfusion support and acute GVHD in paediatric HLA-matched HCT for SCD. Further studies are needed to investigate the pathobiology of this association.     

Partial dysfunction of Treg activation in sickle cell disease

Sickle cell disease (SCD) is a chronic inflammatory disease associated with multiple organ damage, chronic anemia, and infections. SCD patients have a high rate of alloimmunization against red blood cells (RBCs) following transfusion and may develop autoimmune diseases. Studies in mouse models have suggested that regulatory T cells (Treg) play a role in alloimmunization against RBC antigens. We characterized the phenotype and function of the Treg cell population in a homogeneous cohort of transfused SCD patients. We found that the distribution of Treg subpopulations differed significantly between SCD patients and healthy blood donors. SCD patients have a particular Treg phenotype, with strong CTLA‐4 and CD39 expression and weak HLA‐DR and CCR7 expression. Finally, we show that this particular phenotype is related to SCD rather than alloimmunization status. Indeed, we observed no difference in Treg phenotype or function in vitro using autologous feeder cells between strong and weak responders to alloimmunization. Am. J. Hematol. 89:261–266, 2014. © 2013 Wiley Periodicals, Inc.     

Red blood cell alloimmunization in sickle cell disease: The influence of racial and antigenic pattern differences between donors and recipients in Brazil

Red blood cell (RBC) transfusions are widely used in the management of patients with sickle cell disease (SCD). However, repeated RBC transfusions are often complicated by RBC alloimmunization. To investigate whether the frequency of RBC alloimmunization could be accounted for by racial and RBC phenotype differences between donors and recipients in Brazil, in this study we compared the RBC phenotype of 100 SCD patients with that observed in 120 randomly selected blood donors. A comparison of the RBC phenotype between the two groups revealed a statistically significant increase in the frequency of the C antigen in the donor population (P < 0.01), but no significant difference was observed for the A, B, D, c, E, e, K, k, Fy^a, M, N, S, s, and Jk^a antigens. Using standard techniques (indirect antiglobulin test, enzyme treatment, and low-ionic-strength solution) we observed an RBC alloimmunization rate of 12.9% (11/85) in the SCD patients. Fifteen alloantibodies were detected in 11 patients, and most (80%) involved antigens in the Rhesus and Kell systems. This observed RBC alloimmunization rate in SCD patients in Brazil is lower than that reported by studies from North America, suggesting that the requirement for extended antigen-matched RBC transfusion for SCD patients in the setting of a RBC phenotype concordant donor-recipient population may not be cost-effective in some countries. © 1996 Wiley-Liss, Inc.     

Glucose‐6‐phosphate‐dehydrogenase deficient red blood cell units are associated with decreased posttransfusion red blood cell survival in children with sickle cell disease

Chronic transfusion therapy (CTT) for sickle cell disease (SCD) reduces disease morbidity by suppressing the amount of circulating hemoglobin S (HbS)‐containing red blood cells (RBC). The effectiveness of CTT depends on the rate of RBC clearance. Glucose‐6‐phosphate dehydrogenase (G6PD) deficient donor RBC may exhibit increased hemolysis, but it is unknown if transfusion of these units results in less effective transfusion outcomes in SCD. Children with SCD on CTT were followed prospectively for multiple transfusions. G6PD activity of transfused units was measured prior to expiration date. HbA clearance (ΔHbA) was calculated as the difference of estimated posttransfusion HbA to the pretransfusion HbA of the subsequent transfusion episode. Sixty‐two patients received 388 transfusions. Of 755 RBC units, 687 (91%) had normal G6PD (>60% activity), 38 (5%) had moderately low G6PD (10‐60% activity), and 30 (4%) had severely low G6PD (<10% activity). Of 358 evaluable transfusions, 54 (15%) included ≥1 G6PD deficient units, and 22 (6%) had ≥1 severely deficient units. The proportion of the transfusion episode consisting of G6PD deficient units was associated with increased ΔHbA for all G6PD deficient units (P = .05) and for severely G6PD deficient units (P = .0070). In multivariate mixed effects modeling, ΔHbA was positively associated with severely G6PD deficient units (P = .0074) and RBC alloimmunization (P = .03) and negatively associated with recipient splenectomy (P = .015). Higher ΔHbA was associated with higher HbS and reticulocyte counts at the subsequent transfusion episode. In conclusion, G6PD deficient RBC transfusions may have shorter in vivo survival and adversely affect the suppression of sickle erythropoiesis.     

Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease

Sickle cell disease (SCD) patients are at increased risk of red blood cell (RBC) alloimmunization. Recipient inflammatory state at time of transfusion has been shown to regulate alloimmunization in murine models, but evidence is lacking in SCD patients. We retrospectively studied a cohort of alloimmunized SCD patients to determine the influence of pro‐inflammatory SCD‐related complications at time of transfusion on alloimmunization. For each transfusion, the presence of pro‐inflammatory state, degree of RBC antigen matching, unit age, storage solution and alloantibody detection date were ascertained. Transfusion‐associated pro‐inflammatory events were compared between transfusions resulting and not resulting in new alloantibodies. Univariate analysis and multivariate logistic regression were performed. Fifty‐two patients received 3166 pre‐storage leuco‐reduced transfusions of which 128 resulted in alloantibodies. Transfusions during inflammatory events were associated with increased alloantibody risk on univariate and multivariate analysis; acute chest syndrome and vaso‐occlusive crisis showed strongest associations with alloimmunization. Increased antigen matching demonstrated a protective effect on alloimmunization (univariate and multivariate analysis). Although an association was seen between citrate‐phosphate‐dextrose (adenine) stored units and alloimmunization on univariate analysis, no effect was found on multivariate analysis. Identifying recipient pro‐inflammatory states at time of transfusion that promote alloimmunization can impact RBC unit selection decisions for SCD patients at risk for alloimmunization.     

Clinical aspects of platelet transfusion.

Several clinical complications of platelet transfusions relate to contaminating donor leucocytes, and a number of strategies have been devised to leucodeplete platelet products before transfusion. Both alloimmunization to class I human leucocyte antigens (HLA), which causes febrile transfusion reactions and refractoriness to transfused platelets, and transmission of cytomegalovirus have been shown to be reduced by 3-log10 leucodepletion by filtration. Lesser degree of leucodepletion, e.g. by platelet preparation from buffy coats, will control febrile transfusion reactions, but will not reliably prevent other complications. The clinical implications and cost-effectiveness of different strategies of platelet production remain a matter of debate.     

A flow cytometric platelet immunofluorescence crossmatch for predicting successful HLA matched platelet transfusions

Platelet crossmatching may provide a useful way of selecting donors for effective platelet transfusions in patients refractory to random donor platelet concentrates due to alloimmunization. We assessed the predictive value of a flow cytometric platelet immunofluorescence crossmatch test for the outcome of HLA matched platelet transfusions in a group of alloimmunized patients. Platelet immunofluorescence (PIFT) crossmatches were performed for 104 HLA-matched platelet transfusions administered to 30 patients. A negative PIFT crossmatch correctly predicted a successful platelet transfusion (1 h post-transfusion platelet recovery >20%) in 56/75 (75%) cases. We also considered non-immunological factors that, in combination with alloimmunization, might have contributed to an unsuccessful transfusion result, i.e. fever, septicaemia, splenomegaly, disseminated intravascular coagulation and bleeding. The predictive value of a negative PIFT crossmatch was better when these non-immunological factors were absent [48/59 (81%) correct predictions] than when these factors were present [8/16 (50%) correct predictions] (P=0.01; chi-square test). The effect of ABO incompatibility between donor and recipient on the predictive value of the PIFT crossmatch was also analysed. Positive PIFT crossmatches occurred more frequently in ABO incompatible donor–recipient combinations [in 18/28 (64%) cases] than in ABO-compatible donor–recipient combinations [in 11/76 cases (14%)] (P<0.001, chi-square test). Successful platelet transfusions were observed on 53/76 (70%) occasions in ABO compatible transfusions as compared to 16/28 (57%) in ABO incompatible transfusions. This difference was not statistically significant (P=0.23; chi-square test). Consequently, a negative PIFT crossmatch appeared to be non-predictive for the transfusion outcome in cases of ABO incompatibility between donor and recipient. We conclude that the PIFT crossmatch for platelet donor selection in addition to matching for HLA antigens, is predictive for the outcome of ABO compatible transfusions in alloimmunized recipients and prediction levels are increased when non-immunological causes for platelet refractoriness are absent.     

Prevalence of Alloimmunization to Human Platelet Antigen Glycoproteins and Human Leucocyte Antigen Class I in β Thalassemia Major Patients in Western India

Present management of β thalassemia major by regular packed red blood cell (PRBC) transfusions poses risk of alloimmunization not only to red blood cell antigens, but also to human platelet antigens (HPA) and Human leucocyte antigens class I (HLA I). However data in this context is very limited in Indian population. The aim of the study was to determine the prevalence of alloimmunization to HPA and HLA I in β thalassemia major patients who have received multiple PRBC transfusions over the years. A cross sectional study was performed at our tertiary care blood bank. β thalassemia major patients of more than 6 years of age were included who were receiving fresh, leucoreduced and irradiated PRBC units regularly with annual requirement of more than ten PRBC transfusions. A total of 9 out of 80 (11.25 %) patients were found to be alloimmunized for HPA antigens of various specificity and 24 out of 80 (30 %) developed antibodies to HLA I. The awareness of development of alloimmunization to HPA and HLA antigens in multi PRBC transfused thalassemics, despite use of leucofilters will prompt us, to look for improvement in our current PRBC preparations to minimise platelet alloimmunisation. Further studies are required to validate the findings and build the base line data in this regard. This is of importance, especially in view of providing suitable cross-matched platelets when required in future especially when considering future haematopoietic stem cell transplantation (HSCT).     

Transient platelet and HLA antibody formation in multitransfused patients with malignancy

Fifty-nine patients receiving platelet transfusions for bone marrow failure secondary to malignancy were screened at regular intervals for the presence of antibodies to human leucocyte (HLA) and platelet specific antigens. HLA antibodies occurred in 19 patients, 10 of whom also developed platelet specific antibodies. The HLA antibodies disappeared in 10 of 15 patients followed for periods of 2-14 months. In two patients this occurred whilst still receiving platelet transfusions. Antibody reappeared in only two of six patients subsequently transfused. Antibodies to platelet specific antigens were detected in 28 patients. They were transient, often appeared in association with infection, and in 50% of cases tested demonstrated autoantibody activity. There was no association with antibiotic drug therapy, or PFA/EDTA-dependent cryptantigens. Platelet recovery at 1 h or 20 h post transfusion was not significantly reduced in the presence of platelet specific antibodies. These findings have important implications for the selection of platelet donors for alloimmunized recipients.     

Suppression of transfusion-related alloimmunization in intensively treated cancer patients

A retrospective review of HLA antibody testing and transfusion records of 100 cancer patients who required extensive platelet support revealed that 27 of 100 patients exhibited positive HLA antibody tests; only 13 remained positive on repetitive examination, while 88% of aplastic anemia patients so tested were positive. Sixty-five patients with leukemia, 16 with Ewing's sarcoma, and 19 with recurrent undifferentiated lymphoma were studied. Each patient received at least 10 U of platelets (mean of 72). HLA antibodies were detected in 31% (20/65) of the leukemias, 12% (2/16) of the Ewing's, and 26% (5/19) of the lymphoma patients. Fourteen of the 27 patients who developed antibodies became antibody negative again within 2 mo and remained so. There were no significant differences in quantity of platelet transfusions between antibody-negative patients and alloimmunized patients. A smaller group (n = 8) of aplastic anemia patients followed at the NCl exhibited a frequency of alloimmunization of 88% (7/8) after a mean of 44 U of platelets were transfused. Granulocyte transfusions given therapeutically for granulocytopenia and documented infection did not appear to influence HLA antibody formation. These data indicate that significant immunosuppression occurs in intensively treated cancer patients, as measured by their ability to from antibodies to HLA antigens expressed on the surface of transfused platelets.     

The alloimmunized patient: effective transfusion support and newer experimental approaches.

Refractoriness occurs in a proportion of patients who receive multiple platelet transfusions. Alloantibodies, in particular those directed against the class I human leucocyte antigens (HLA) present on the platelet surface, are frequently associated with accelerated platelet destruction and transfusion failure. Compatible platelets for transfusion may be found by selecting donations from HLA-typed individuals, crossmatching patients' sera against donor lymphocytes and platelets or both. Maintaining a large panel of HLA-typed apheresis donors is expensive and some mismatching is inevitable due to the polymorphic nature of the HLA system. Cross-matching may improve the outcome when HLA-matched donations are transfused and may also be a cost-effective strategy for the selection of compatible untyped platelets. Administration of intravenous immunoglobulin, plasma exchange and ex vivo removal of platelet HLA have been employed successfully in a few refractory alloimmunized patients but do not yet have an established role. Experimental studies in animal models suggest that it may be possible to induce tolerance to HLA and prevent alloimmunization.