Recipient factors influencing red blood cell alloimmunization

Red blood cell (RBC) alloantibodies develop in a subset of individuals following exposure to non‐self RBCs through transfusion, pregnancy or other activities; these antibodies can lead to difficulty locating compatible RBCs, acute or delayed haemolytic transfusion reactions, or haemolytic disease of the newborn. Alloimmunization is underestimated due in part to antibody evanescence, the random nature of post‐transfusion antibody screens, fragmented medical care and the lack of widespread antibody registries. Factors that influence who will develop detectable alloantibodies are not well understood. Transfusion burden is one risk factor for alloimmunization, though many highly transfused individuals never form alloantibodies despite exposure to many RBC units (and many non‐self blood group antigens). Individuals with sickle‐cell disease (SCD) and myelodysplastic syndrome (MDS) are more likely to form RBC alloantibodies than most other patient populations. Individuals with rheumatologic and other forms of autoimmunity, though not chronically transfused, are also at higher‐than‐average risk of forming RBC alloantibodies. Inflammation, in a broad sense, is one common thread amongst these diagnoses associated with high prevalence rates of RBC alloimmunization. Reductionist murine models support some types of inflammation (including viral‐like stimuli) around the time of RBC exposure as being associated with an increased likelihood of alloantibody formation. Strategies other than transfusion avoidance or extended antigen matching beyond ABO/Rh would be beneficial to prevent new RBC alloantibody formation, especially in patients at highest risk.     

Red blood cell alloimmunization and antigen matching in sickle cell disease – the African perspective

In sickle cell disease (SCD), blood transfusion facilitates improved blood and tissue oxygenation, reduces the propensity to sickling by diluting host cells, and suppresses the production of red blood cells (RBCs) containing sickle haemoglobin (HbS). Delivery of RBC transfusions to patients with SCD varies by method (simple vs. exchange) and frequency (episodic vs. chronic). However, due to the genetic differences between blood donors and recipients, repeated transfusions increase the risk of developing alloantibodies to RBC antigens. The antigens most frequently involved belong to the Rh, Kell, Kidd, Duffy, Lewis, and MNS blood group systems. Consequences of RBC alloimmunization include delays and difficulties in obtaining compatible blood for future transfusions, the occurrence of delayed haemolytic transfusion reactions (DHTRs), the hyperhaemolysis syndrome and autoimmunization. In Europe and USA, RBC alloimmunization rates ranging from 18% to 76% have been reported in SCD while other multiply transfused (OMT) patients had alloimmunization rates of 5% to 20% indicating that SCD patients are at a higher risk of developing RBC alloantibodies. To prevent alloimmunization in SCD patients, the standard practice in Europe and USA is to determine their extended RBC phenotype (ABO, Rh, Kell, Kidd, Duffy, Lewis, MNS) before commencing transfusion therapy and perform antigen matching for C, E and K antigens for patients without prior alloantibody formation. However in Africa, lower RBC alloimmunization prevalence rates of 6–10% have been reported in SCD patients and no differences were observed between SCD and OMT patients. This may be explained by the presumed high phenotypic compatibility between donors and SCD patients who were all Black Africans. Also, a low transfusion load (a median 3 U of blood were transfused) in SCD patients might have led to the poor response to alloantigenic challenge. Anti-K alloimmunization was notably rare among African SCD patients compared to anti-S. In many African countries, pre-transfusion immunohaematologic testing includes neither the detection of RBC alloimmunization nor preventive antigen matching. Most transfusion laboratories are understaffed and underequipped; they perform ABO/D typing plus room temperature saline cross-matches and do not screen for RBC alloantibodies. Hence, immunized SCD patients are not diagnosed and do not have the opportunity of receiving antigen-negative blood. Furthermore, data on the occurrence of DHTRs are lacking. Introducing pre-transfusion RBC alloantibody screening in all African countries will significantly improve the transfusion management of SCD patients. A program of limited phenotype matching for C, E and S antigens is recommended to prevent additional alloantibody formation in immunized SCD patients in Africa.     

Utilisation patterns of group O red blood cell transfusion by ABO and D non-identical recipients in large academic hospital

ObjectivesSeveral studies have raised concerns that transfusion of O red blood cells (RBCs) to ABO and D non-identical recipients can intensify group O inventory shortages. The aim of this study was to retrospectively analyse particular clinical indications and polices responsible for O RBCs use by ABO and D non-identical recipients, as well as to assess the impact of this practice on the overall utilisation of O RBCs.Material and methodsData of all transfused RBCs from 2014 to 2018 were extracted from the comprehensive database of transfusion service. Extracted variables included date of transfusion, ABO and D group of the transfused RBCs and recipients, recipient's demographic, and specific characteristics regarding transfusion requirements.ResultsOver a 5-year period, 124,220 RBCs were transfused: 38,962 (31.4%) group O D+ and 9109 (7.3%) group O D?. ABO and D non-identical recipient received 4842 (10.1%) of all administered O RBCs: 2880 (7.4%) of all transfused O D+ and 1962 (21.5%) of all transfused O D? RBCs. The common indications for this practice were: ABO and D mismatched hematopoietic stem cell transplantation (HSCT) (52.5%), infants under the age of 4 months (18.6%), shortage of ABO identical RBCs (9.0%), phenotype-matched RBCs (8,1%), and urgent transfusion (7.2%).ConclusionsA significant proportion of O RBCs was transfused to ABO and D non-identical recipients, mainly due to transfusion of ABO and D mismatched HSCT recipients. However, the proportion of all transfused RBCs O D+ and especially O D? remained relatively low.     

In search of red blood cells for alloimmunized patients with sickle cell disease

Patients with sickle cell disease (SCD) typically require transfusions with RBC components, which exposes them to numerous, possible foreign antigens and potentially causes them to produce an antibody or antibodies to the antigens they lack. As transfusion of these patients increases, the likelihood that they will produce an initial antibody or additional antibodies increases. Once a clinically significant antibody is produced, units of RBCs that lack the associated antigen should be transfused. Often patients with SCD present to transfusion service with numerous antibodies in their serum, making the search for compatible RBCs a challenge. The American Rare Donor Program (ARDP) has been used to search for RBCs to meet transfusion needs of this patient population. Between January 2005 and June 2006, approximately 33 percent of the requests to the ARDP for RBC components were alloimmunized patients with SCD. Of these requests, 94.9 percent were completely or partially filled; requests for r"r", Hy-, and E-, hrS- units of RBCs were among the most difficult to fill. This article will discuss the use and effectiveness of the ARDP and testing laboratories associated with the National Reference Laboratory for Blood Group Serology at the American Red Cross in obtaining compatible RBCs for alloimmunized patients with SCD.     

Directed blood donor program decreases donor exposure for children with sickle cell disease requiring chronic transfusion

In children with sickle cell disease (SCD), primary and secondary prevention of strokes require indefinite regular blood transfusion therapy. The risks associated with repeated transfusions include alloimmunization and increased donor exposure. The Charles Drew Program is a directed blood donor program designed to lower donor exposure, decreasing the associated complications of transfusion; however, no evidence exists demonstrating the magnitude of the benefit to the recipient. Further, the use of extended red blood cell (RBC) antigen matching for C, E, and K has been well documented in a clinical trial setting but not extensively evaluated in a standard care setting. The goal of this study is to assess the effectiveness in reducing alloimmunization when matching for C, E, and K and the magnitude of the decrease in donor exposure in a directed blood donor program. The rate of alloimmunization and reduction of donor exposure were determined during the course of 1 year in a cohort of children with SCD who received regular directed donor blood transfusions. A total of 24 recipients were in the program, 16 females and 8 males, 4 to 20 years of age. During 2008, alloimmunization was 0 percent and donor exposure was reduced by 20 percent, compared with usual care. Extended RBC antigen matching has the same benefit as in a clinical trial setting for patients with SCD receiving blood transfusion therapy. Despite significant effort, we only achieved a modest decrease in donor exposure and cannot determine the immediate benefit of a directed blood donor program.     

The impact of transfused blood products on deceased donor HLA typing

Accurate deceased donor HLA typing assumes that the blood sample tested contains only DNA from the organ donor. Prior to procurement, many organ donors are transfused at least one unit of red blood cells (RBC). Non-organ donor DNA acquired from transfusions may result in incorrect and/or ambiguous HLA typing. To address this question, we investigated the impact of RBC transfusion on organ donor HLA typing by using different in vitro transfusion models: leukoreduced (LR) and non-LR RBCs. Various quantities of LR and non-LR RBCs were added to normal peripheral blood and HLA typing was performed by real time PCR. Our results show that HLA typing of deceased donors can be impacted dependent upon the type and quantity of transfused RBCs. Importantly, if LR RBCs are given, HLA typing is unlikely to be affected, precluding the need to delay typing and obtain an alternative source of donor DNA.     

‐318C/T polymorphism of the CTLA‐4 gene is an independent risk factor for RBC alloimmunization among sickle cell disease patients

Cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) molecule is expressed on T‐lymphocyte membrane and negatively influences the antigen‐presenting process. Reduced expression of CTLA‐4 due to gene polymorphisms is associated with increased risk of autoimmune disorders, whose physiopathology is similar to that of post‐transfusion red blood cell (RBC) alloimmunization. Our goal was to evaluate if polymorphisms of CTLA‐4 gene that affect protein expression are associated with RBC alloimmunization. This was a case–control study in which 134 sickle cell disease (SCD) patients and 253 non‐SCD patients were included. All patients were genotyped for the polymorphisms 49A/G and ‐318C/T of CTLA‐4 gene. The genotype frequency of ‐318C/T differed significantly between alloimmunized and nonalloimmunized SCD patients, irrespective of clinical confounders (p = .016). SCD patients heterozygous for ‐318T allele presented higher risk of alloantibody development (OR: 5.4, CI: 1.15–25.6). In conclusion, the polymorphism ‐318C/T of CTLA‐4 gene is associated with RBC alloimmunization among SCD patients. This highlights the role played by CTLA‐4 on post‐transfusion alloantibody development.     

Phenotypic differences of CD4+ T cells in response to red blood cell immunization in transfused sickle cell disease patients

Alloimmunization against red blood cells (RBCs) is the main immunological risk associated with transfusion in patients with sickle cell disease (SCD). However, about 50–70% of SCD patients never get immunized despite frequent transfusion. In murine models, CD4⁺ T cells play a key role in RBC alloimmunization. We therefore explored and compared the CD4⁺ T‐cell phenotypes and functions between a group of SCD patients (n = 11) who never became immunized despite a high transfusion regimen and a group of SCD patients (n = 10) who had become immunized (at least against Kidd antigen b) after a low transfusion regimen. We studied markers of CD4⁺ T‐cell function, including TLR, that directly control lymphocyte function, and their spontaneous cytokine production. We also tested responders for the cytokine profile in response to Kidd antigen b peptides. Low TLR2/TLR3 expression and, unexpectedly, strong expression of CD40 on CD4⁺ T cells were associated with the nonresponder status, whereas spontaneous expression of IL‐10 by CD4⁺ T cells and weak Tbet expression were associated with the responder status. A Th17 profile was predominant in responders when stimulated by Jb^k. These findings implicate CD4⁺ T cells in alloimmunization in humans and suggest that they may be exploited to differentiate responders from nonresponders.     

Effects of genetic,epigenetic, and environmental factors on alloimmunization to transfused antigens: Current paradigms and future considerations

Transfused red blood cells, platelets, or coagulation factors have the capacity to induce alloantibodies, which once formed, can be a clinical barrier to future transfusion therapy and/or transplantation. Large observational studies over the last 50 years have characterized some of the general properties of transfusion induced alloimmunization, which appear to vary to a considerable extent from what is generally observed for human responses to other immunogens, such as microbial pathogens and vaccines. Transfused cells and factor only induce immune responses in the minority of recipients. There are data to suggest that differences in the unit may play a role. However, there are clearly differences in recipient biology, as once a recipient makes one antibody they are much more likely to make additional antibodies; indeed, recipients have been categorized as “responder” and “non-responder” by the field. Recent mechanistic studies have begun to define potential causes for such differences in alloimmunization from patient to patient, but much progress needs to be made to understand how, why, and in whom alloimmunization occurs. This review gives a general background on immunology in the context of transfusion, summarizes recent progress in the field, and discusses future directions for exploration. Particular attention is paid to the general concept that the human immune system is melded by the wide range of antigens encountered in our environment, and that the effects of such on the immune system may have a profound effect upon response to transfused cells.     

Fatal delayed transfusion reaction in a sickle cell anemia patient with Serratia marcescens sepsis

Patients with sickle cell anemia may require repeated red cell transfusion, putting them at risk for minor blood group alloimmunization and the development of delayed hemolytic transfusion reactions. Although Streptococcus pneumoniae is the most common cause of life-threatening infection in patients with sickle cell anemia, those who have been recently hospitalized are at risk for infection with resistant hospital-associated organisms, and blood transfusion may put the patient at risk of infection with transfusion-associated organisms such as Serratia marcescens and Yersinic enterocolitica. We recently cared for an adolescent with sickle cell anemia who presented to the emergency department with a severe, delayed hemolytic transfusion reaction and Serratia marcescens infection. The patient had been discharged from the hospital five days previously, and had been transfused and treated with antibiotics while hospitalized. In addition to demonstrating the potential severity of delayed hemolytic transfusion reactions, our case illustrates the importance of providing relatively broad-spectrum antibiotic coverage to patients with sickle cell anemia and possible infection who have recently been hospitalized.     

ABO blood group should be considered and reported when red blood cell exchange transfusion is used to treat Plasmodium falciparum Malaria patients

Laboratory and epidemiologic studies have clarified how persons born with malaria-resistant red blood cells (RBCs)–like group-O, sickle-trait, and C-trait RBCs–are protected against death or severe disease due to Plasmodium falciparum (Pf) infection. Compared to malaria-promoting RBCs–like non-O or hemoglobin-AA RBCs–inborn RBC protection against severe Pf malaria can be profound: up to 10-fold greater. Given that “the Berlin patient” success showed patients do not have to be born with disease-resistant cells to benefit from them, why have the biologically plausible benefits of exchange transfusion (ET) of malaria-resistant RBCs not yet been evaluated? Unfortunately, a 2013 ET-for-malaria meta-analysis could not quantify the impact on mortality of ET of malaria-resistant RBCs because RBC malaria resistance variables (ABO group, hemoglobin type, enzyme levels, etc.) had not been reported in any of the ET studies used in that meta-analysis. To promote evaluation of the therapeutic impact of specific malaria-resistant RBCs, we urge clinicians to always report ABO blood group (and all other RBC malaria-resistance variables they are aware of) when they use ET to rescue Pf-infected patients. Prudent selection of donor RBCs has successfully optimized ET for sickle cell disease patients, and this precedent suggests selection of special malaria-resistant donor RBCs may optimize ET for Pf-malaria patients. Given that ET is used worldwide as a rescue adjunct, we feel it is most prudent to now assume–until proven otherwise–that considering and reporting the Pf-malaria-resistance variables of the RBCs to be transfused–at least ABO status–will help optimize ET-for-malaria.     

Transfusion of multiple units of Js(b+) red blood cells in the presence of anti-Jsb in a patient with sickle beta-thalassemia disease and a review of the literature

Jsb is a high-frequency antigen. Anti-Jsb is a rare alloantibody, and its clinical significance is poorly documented. We report a case in which a 12-year-old boy of Nigerian descent with sickle beta- thalassemia presented with multiple alloantibodies, including a panagglutinin and acute chest syndrome, necessitating the emergent transfusion of five units of phenotype-similar, crossmatchincompatible RBCs, four of which were given during an exchange transfusion. The patient was later found to have anti-Jsb. In addition to routine serologic methods to study the patient's RBCs and plasma, a monocyte monolayer assay (MMA) was performed on the patient's samples obtained 2 and 9 days after transfusion of the Js(b+) RBCs to determine the potential clinical significance of the anti-Jsb. Various laboratory parameters including quantitative hemoglobin fraction analyses were used to monitor for increased RBC destruction. The MMA reactivity of the patient's anti-Jsb increased from 2.3 percent on day 2 after transfusion to strongly positive at 88 percent and 66.5 percent (with and without the addition of fresh serum) 1 week later. MMA reactivity of greater than 5 percent is associated with increased RBC destruction. There was no clinical or laboratory evidence of increased hemolysis above baseline. However, decreased RBC survival was suggested by the relatively brisk decrease of the HbA1 fraction after the transfusions. The current case and others reported in the literature suggest that anti-Jsb may have limited potential for causing overt hemolysis. However, in patients with underlying hematologic disease, even mildly increased RBC destruction may pose problems clinically,and thus transfusion of Js(b+) RBCs should be avoided. In emergent situations, the potential of adverse effects of transfusing incompatible units should be balanced against the risk of withholding transfusion. Family members, especially siblings, should be considered as potential designated donors for patients with antibodies directed against high-frequency antigens. Available reports on anti-Jsb in the literature are also reviewed.     

Viral seroprevalence, transfusion and alloimmunization in adults with sickle cell anemia in Guadeloupe]

We retrospectively studied the prevalence of anti HIV 1 and 2, anti-HTLV-I, anti-Hepatitis B and C viruses (HBV and HCV) antibodies, anti-HBV vaccinal coverage, transfused patients and alloimmunizations frequencies among adult sickle cell patients attending the sickle cell center (SCC) of Guadeloupe. The data were collected from the medical files of the centre. Among the studied samples (n = 331) no transfusional HIV contamination was observed. All patients with HTLV-I (n = 11, 3.3% of whole sample) and anti-HCV (n = 9, 2.7%) positive serology had transfusion history. Five patients (1.5%) had an active hepatitis B. Vaccination against HBV efficiently protected 247 patients (74.4%) and 57 had post-hepatitis B antibodies. We observed that 213 patients (64%) had a history of transfusion (88% of SS patients and 36% of the SC patients, p < 0.05). Fifty-four patients (16%) presented alloimmunization, 4 of them have never been transfused. These results show that it is still necessary to optimise transfusion protocol and their safety, and to diagnose viral contamination in transfused sickle cell patients.     

The significance of a positive DAT in thalassemia patients

The DAT is performed for the detection of antibody or complement on the surface of RBCs. Our institution previously performed DATs on all chronically transfused thalassemia patients before each transfusion episode to detect early alloimmunization. The medical records of all thalassemia patients treated at our institution from 2004 to 2007 were reviewed to determine the significance of the high rate of positive DATs (52.5% of 80 patients). The majority of IgG-reactive DATs were associated with a nonreactive eluate (65.4% of 286 eluates performed). A positive DAT was significantly associated with splenectomy (χ2 = 15.4; p < 0.001), elevated IgG levels (χ2 = 26.8; p < 0.001), HCV (χ2 = 20.7; p < 0.001), and warm autoantibody (χ2 = 5.87; p = 0.03). Multivariate analysis revealed that only HCV (OR, 5.0; p = 0.037) and elevated IgG levels (OR, 9.0; p = 0.001) were independently associated with a positive DAT. Alloimmunized thalassemic patients were more likely to have a positive DAT than nonalloimmunized patients, but this association was not significant (OR, 2.2; p = 0.11). A positive DAT did not correlate with decreased response to transfusion, RBC survival, hemolysis, or increased transfusion requirements. Only two cases of early alloimmunization were detected by DAT among 288 DAT-positive samples studied during 4 years. This study demonstrated that the routine performance of DATs on pretransfusion specimens in thalassemic patients has limited clinical utility, and the elimination of this test will improve turnaround time and decrease costs.     

Indicators of clinically significant red cell antibodies produced by sensitized lymphocytes in liver transplant patients

It has been documented that transplanted livers can carry sensitized lymphocytes that subsequently produce red cell antibodies. We evaluated immunohematological variables in liver donors and recipients for indicators that might be predictive of serological red blood cell (RBC) destruction mediated by the passenger lymphocytes. Organ donor sera with antibody scores greater than ( > ) 60 correlated with a positive direct antiglobulin test (DAT) and need for increased RBC transfusion in liver transplant recipients. We therefore propose an antibody screen on all potential liver donors and titration of unexpected alloantibodies; titration of ABO antibodies of liver donors who demonstrate minor ABO-incompatibilities with their recipients; and, when needed, transfusion of group O RBCs to recipients of livers from donors with minor ABO-incompatibility who have antibody scores >60.     

TRIM21 Polymorphisms are associated with Susceptibility and Clinical Status of Oral Squamous Cell Carcinoma patients

Squamous cell cancer of head and neck (HNSCC) is the sixth most common malignancy worldwide. One of the most common HNSCC types is oral squamous cell carcinoma (OSCC), which is the fifth leading cause of cancer death in Taiwan. Tripartite motif 21 (TRIM21) has been reported to play an important role in different cancer types. We found a correlation between TRIM21 and survival of HNSCC patients, but little information exists about how altered TRIM21 expression contributes to tumorigenesis. Thus, we investigated the combined effect of TRIM21 polymorphisms and exposure to environmental carcinogens on the susceptibility and clinicopathological characteristics of OSCC. Two single-nucleotide polymorphisms (SNPs) of TRIM21 (rs4144331, rs915956) from 1194 healthy controls and 1192 OSCC patients were analyzed by real-time PCR. Among 1632 smokers, TRIM21 polymorphism carriers with the betel-nut chewing habit had a ~4.8-fold greater risk of OSCC than TRIM21 wild-type carriers without the betel-nut chewing habit. After adjusting for other covariants, OSCC patients with G/T at TRIM21 rs4144331 had a high risk for distant metastasis compared with G/G homozygotes. This study is the first to examine the risk factors associated with TRIM21 SNPs in OSCC progression and development. Thus, our findings suggest that this study is the first to examine the risk factors associated with TRIM21 SNPs in OSCC progression and development and suggest that interactions between mutant genes may alter the susceptibility to OSCC.     

Case report: immune anti-D stimulated by transfusion of fresh frozen plasma

FFP has occasionally been reported to generate an immune response to RBC antigens (e.g., anti-D and anti-Fya). The Council of Europe requires that each unit of FFP have less than 6 x 10(9)/L RBCs. However, there is considerable variation internationally in the method of production and the level and assessment of RBC contamination of FFP. This study reports the case of a 63-year-old group B, D- man who received multiple transfusions of D- blood products over a 4-month period. Seven months later the patient's antibody screen remained negative and he was transfused with seven units of D- RBCs and six units of FFP, four of which were D+. Two months later anti-D, -E, and -K were detected in his plasma. Although the anti-E and anti-K could have resulted from transfusion of antigen-positive RBCs, the anti-D could have resulted only from transfusion of the D+ FFP. The D status of FFP is currently not considered when selecting products for transfusion even though the D antigen is highly immunogenic and the level of RBC contamination of FFP is not always known. This case highlights that transfusion of FFP is a stimulus for RBC antibodies and that when a patient has had a recent transfusion of FFP, consideration should be given to obtaining a sample for pretransfusion testing within 3 days before a scheduled RBC transfusion. In addition, the D status of FFP should be considered before administering FFP to premenopausal D- women.     

Transfusion practices for patients with sickle cell disease at major academic medical centers participating in the Atlanta Sickle Cell Consortium

The Atlanta Sickle Cell Consortium represents more than 2600 pediatric and adult patients with sickle cell disease (SCD) in the metropolitan Atlanta, Georgia, area receiving care at four major locations, each providing comprehensive care 24 hours a day, 7 days a week. Both transfusion services that support these sites use two levels of prospective phenotype matching to decrease the rates of alloimmunization. Although exact rates are unknown and are currently under investigation, alloimmunization occurs infrequently with the exception of chronically transfused SCD patients, who represent the minority of active SCD patients. With increasing availability, red blood cell genotyping will be used in the near future both for determination of predicted patient phenotypes and for provision of genotypically matched donor units.     

Results of HLA antibody testing using ELISA vs the fluorescent bead method and retrospective review of data for recipients of packed RBCs and platelets from male HLA-immunized donors

We reviewed HLA antibody testing results using an enzyme-linked immunosorbent assay (ELISA) for all male blood donors at our institution during a 3.5-month period to look for HLA immunization. Confirmatory testing of 33 blood samples positive for HLA class I and/or II antibodies was performed using the fluorescent bead method. A retrospective review of recipients of packed RBCs and platelets processed from these 33 HLA-immunized male donors were conducted to identify transfusion-related acute lung injury and cognate antigens. The agreement rates between the methods for HLA class I and II antibodies were 21% (7/33) and 6% (2/33), respectively. We noted HLA antibodies in the male donors corresponding to cognate antigens in 2 recipients of packed RBCs and in 3 recipients of platelets. Of 8 donors positive for HLA antibodies, 5 did not have a history of blood transfusion. We conclude that ELISA was too sensitive and had a high false-positive rate for the detection of HLA class II antibodies.     

Immunoprophylaxis using intravenous Rh immune globulin should be standard practice when selected D-negative patients are transfused with D-positive random donor platelets

A 67-year-old female developed excessive bleeding and thrombocytopenia following cardiovascular surgery. Her blood type was group A, D-. The only platelet products available in the transfusion service were random donor platelet concentrates from D+ donors. She was transfused with a pool of 6 D+ random donor platelet concentrates. Anti-D undetected in her pretransfusion serum by solid-phase antibody screen was present 11 days later. Retrospectively, the patient provided a history of having two pregnancies more than 40 years ago, prior to the availability of immunoprophylaxis by Rh immune globulin (RhIG). Although studies have shown that as many as 19 percent of D- people may develop anti-D following transfusion of platelets from D+ donors, there is no specific standard requiring immunoprophylaxis with RhIG to prevent Rh alloimmunization after transfusion of random donor platelet concentrates from D+ donors. In contrast, vigorous efforts are routine for preventing Rh alloimmunization in D- patients requiring red cell transfusions or D- females during pregnancy or after delivery of D+ newborns. The absence of a comparable practice standard for platelet transfusions is based, in part, on concern that intramuscular injections of conventional RhIG may cause local hemorrhage in thrombocytopenic persons. The recent availability of a Food and Drug Administration-approved preparation of intravenous RhIG makes Rh immunoprophylaxis in thrombocytopenic patients safe and practical. We recommend that intravenous RhIG be considered if it is necessary to transfuse random donor platelet concentrates from D+ donors to D- recipients. As a minimal standard, intravenous RhIG should be administered to all D- females of childbearing age who are recipients of pools of random donor platelet concentrates from D+ donors.