Anti-D immunization after D positive platelet transfusions in D negative recipients: A systematic review and meta-analysis.

BACKGROUND: Anti-D can be formed after D-incompatible platelet transfusions due to contaminating D+ red blood cells. These antibodies are of particular importance in women of childbearing potential, because anti-D is most often involved in severe cases of hemolytic disease of the fetus and newborn. This systematic review determined the frequency of anti-D after D+ platelet transfusions and risk factors for D alloimmunization. STUDY DESIGN AND METHODS: Relevant literature was searched using PubMed, Embase and Web of Science until December 2022. Overall anti-D frequency and risk factors were estimated using a random effects meta-analysis. RESULTS: In 22 studies, a total of 3028 D- patients received a mean of six D+ platelet transfusions. After a mean follow-up of seven months 106 of 2808 eligible patients formed anti-D. The pooled anti-D frequency was 3.3% (95% CI 2.0-5.0%; I2 71%). After including only patients with an undoubtable follow-up of at least 4 weeks, 29 of 1497 patients formed anti-D with a pooled primary anti-D rate of 1.9% (95% CI 0.9-3.2%, I2 44%). Women and patients receiving whole blood derived platelets had two and five times higher anti-D rates compared with men and patients receiving apheresis derived platelets, respectively. DISCUSSION: Anti-D immunization is low after D incompatible platelet transfusions and dependent on recipients' sex and platelet source. We propose anti-D prophylaxis in girls and women, capable of becoming pregnant in the future, that received D+ platelets, regardless of platelet source, to reduce the risk of anti-D induced hemolytic disease of the fetus and newborn.

Extended red blood cell matching for all transfusion recipients is feasible.

OBJECTIVE: To demonstrate the feasibility and effectiveness of extended matching of red blood cells (RBC) in practice. BACKGROUND: At present, alloimmunisation preventing matching strategies are only applied for specific transfusion recipient groups and include a limited number of RBC antigens. The general assumption is that providing fully matched RBC units to all transfusion recipients is not feasible. In this article we refute this assumption and compute the proportion of alloimmunisation that can be prevented, when all donors and transfusion recipients are typed for A, B, D plus twelve minor blood group antigens (C, c, E, e, K, Fya , Fyb , Jka , Jkb , M, S and s). METHODS: We developed a mathematical model that determines the optimal sequence for antigen matching. The model allows for various matching strategies, issuing policies and inventory sizes. RESULTS: For a dynamic inventory composition (accounting for randomness in the phenotypes supplied and requested) and an antigen identical issuing policy 97% and 94% of alloimmunisation events can be prevented, when respectively one and two RBC units per recipient are requested from an inventory of 1000 units. Although this proportion decreases with smaller inventory sizes, even for an inventory of 60 units almost 50% of all alloimmunisation events can be prevented. CONCLUSION: In case antigen of both donors and recipients are comprehensively typed, extended preventive matching is feasible for all transfusion recipients in practice and will significantly reduce transfusion-induced alloimmunisation and (alloantibody-induced) haemolytic transfusion reactions.

Reduction of anti-K-mediated hemolytic disease of newborns after the introduction of a matched transfusion policy: A nation-wide policy change evaluation study in the Netherlands.

BACKGROUND: During pregnancy, maternal red blood cell (RBC) antibodies can lead to life-threatening fetal hemolysis and anemia. Women can become immunized by a pregnancy or an unmatched transfusion. Our aim was to quantify the effect of a nationwide K-matched transfusion policy for women of childbearing age potential to prevent K-immunization in pregnancy. STUDY DESIGN AND METHODS: In this nation-wide policy change evaluation study we determined the occurrence of RBC antibodies before and after introduction of a K-matched transfusion policy and evaluated the cause K alloimmunization 10 years after introduction of this measure. K-matched transfusion for females under 45 years of age is advised in the Dutch transfusion guideline since 2004. We used laboratory data from pregnancies with RBC antibodies identified in the period 1999-2018 obtained as part of a population-based screening program in the Netherlands. RESULTS: Tests of 36 286 pregnancies produced a positive antibody screening result which concerned anti-K in 1550 pregnancies. The occurrence of anti-K decreased from 67.9 to 20.2 per 100 000 pregnancies. The relative risk reduction was 0.70 which largely exceeded the relative risk reduction of 0.27 for antibodies against RBC antigens for which no preventive matching is required. The number of pregnancies at risk for anti-K-mediated disease decreased from 9.7 to 4.2 per 100 000 pregnancies. CONCLUSIONS: A K-matched transfusion policy is associated with a major decrease in a number of pregnant women with anti-K and pregnancies at risk for anti-K-mediated disease. A relatively simple measure is now shown to impact prevention of hemolytic disease in the fetus and newborn.

Prevalence of red-blood-cell and non-red-blood-cell-targeted autoantibodies in alloimmunized postpartum women.

BACKGROUND AND OBJECTIVES: Alloantibodies against red-blood-cell (RBC) antigens often coincide with alloantibodies against leucocytes and platelets and sometimes with autoantibodies towards various antigens. Chimerism may be one of the factors responsible for the combination of allo- and autoantibodies. Women with alloantibodies against RBC antigens causing haemolytic disease of the fetus and neonate may need to receive intrauterine transfusions. These transfusions increase not only maternal antibody formation but also fetomaternal bleeding and may enhance fetal chimerism. We determined the prevalence of and risk factors for autoantibodies against some common clinical target antigens, in alloimmunized women after IUT. MATERIALS AND METHODS: We tested for autoantibodies against RBC, anti-thyroid peroxidase, anti-extractable nuclear antigens, anti-cyclic citrullinated proteins and anti-tissue transglutaminase. Women with and without autoantibodies were compared for age; number of RBC alloantibodies, pregnancies and IUTs, and other factors that may play a role in immunization. RESULTS: Non-RBC-targeted autoantibodies were present in 40 of 258 tested women (15·5%, with 90% anti-TPO specificity), comparable to the prevalence reported in healthy Dutch women of these ages. Surprisingly, compared with women who had a single RBC alloantibody, a significantly higher proportion of women with multiple RBC alloantibodies had autoantibodies (5·3% and 18·4%, respectively; odds ratio 4·06, 95% CI: 1·20-13·7). Other characteristics of women with and without autoantibodies were not different. CONCLUSION: Multiple RBC alloantibodies after extensive allogeneic exposure during pregnancy and presumed increased fetomaternal chimerism are not associated with (selected) autoantibodies. Lack of allo-RBC multi-responsiveness seems associated with decreased auto(-TPO) antibody formation.

Exposure to non-inherited maternal antigens by breastfeeding affects antibody responsiveness.

The observation, by Ray Owen and colleagues in 1954, that D-negative women were less likely to form anti-D antibodies against their D-positive fetus if their mother possessed the D-antigen, was not found in all later studies. We hypothesized that breastfeeding, received by the mother, may affect her immunity against non-inherited maternal red blood cell antigens. We studied a cohort of 125 grandmother-mother-child combinations, from a follow-up study of mothers after intrauterine transfusion of the fetus for alloimmune hemolytic disease. For mismatched red blood cell antigens the mother was exposed to, whether or not antibodies were formed, we determined whether her mother, the grandmother, carried these antigens. The duration for which the mothers were breastfed was estimated by way of a questionnaire. Using multivariate logistic regression analyses, the interaction term (non-inherited maternal antigen exposure by categorized breastfeeding period) showed that a longer breastfeeding period was associated with decreased alloimmunization against non-inherited maternal antigens (adjusted odds ratio 0.66; 95% confidence interval 0.48-0.93). Sensitivity analysis with dichotomized (shorter versus longer) breastfeeding periods showed that this lower risk was reached after two months (aOR 0.22; 95% CI 0.07-0.71) and longer duration of breastfeeding did not seem to provide additional protection. These data suggest that oral neonatal exposure to non-inherited maternal red blood cell antigens through breastfeeding for at least two months diminishes the risk of alloimmunization against these antigens when encountered later in life.

Red blood cell alloimmunization and minor red blood cell antigen phenotypes in transfused Ghanaian patients with sickle cell disease.

BACKGROUND: The routine pretransfusion investigations in Southern Ghana involve only ABO-D blood group typing and ABO compatibility testing without screening for irregular red blood cell (RBC) antibodies. The prevalence and specificities of RBC antibodies and frequencies of most minor blood group antigens in transfused patients with sickle cell disease (SCD) in Ghana are not known and are the objectives of this study. STUDY DESIGN AND METHODS: This was a cross-sectional study that investigated transfused patients with SCD for the presence of irregular RBC antibodies and Rhesus, Kell, Duffy, Kidd, and Ss antigens. RESULTS: From a total of 154 patients (median age, 9 years), 10 patients (6.5%) possessed 13 antibodies, predominantly against D, C, and E antigens. In three patients, the antibodies (anti-D, anti-D + C, and anti-C + e) were against antigens they possessed by serology. Genotyping showed that two of these patients had variant RHCE genes that encode for weak and partial e antigens and one patient had a partial RHC gene. Frequencies of most RBC antigens were comparable with frequencies established among the African American population; however, K-k- and Jk(a-b-) phenotypes were more frequent and were present in 21% and 17% of patients, respectively. CONCLUSION: The prevalence of RBC alloimmunization in transfused Ghanaian patients with SCD was 6.5% and the majority of antibodies were against antigens of the Rh system. Our findings stress the need to include pretransfusion testing for RBC antibodies in patients with SCD, to improve transfusion safety.

Frequency and characterization of RHD variants in serologically D- Surinamese pregnant women and D- newborns.

BACKGROUND: Numerous RHD variant genes affect the expression of D on the red blood cell surface. In Suriname, 4.3% of pregnant women were D-, ranging from virtually zero to 7% among ethnic groups. Characterization of RHD variants, which are associated with a variable potential to induce anti-D, is of practical clinical importance especially in case of limited access to preventive measures. Here we report on the occurrence of RHD variant genes in Surinamese serologically D- pregnant women and their D- newborns from different ethnic groups. STUDY DESIGN AND METHODS: The RheSuN study is a cross-sectional cohort study in D- pregnant women and their newborns, who visited hospitals in Paramaribo, Suriname, during routine pregnancy care. The presence of RHD variants was investigated using quantitative polymerase chain reaction targeting RHD Exons 5 and 7 and RH-multiplex ligation-dependent probe amplification. RESULTS: Seven RHD variant genes were detected in 35 of 84 women and four RHD variant genes in 15 of 36 newborns. The RHD*03 N.01 and RHD*08 N.01 variants represented 87% of a total of 62 variant genes. Variants were comparably frequent among ethnicities. In four cases genotyping would have changed anti-D prophylaxis policy: one woman with a RHD*01EL.01 variant, not associated with anti-D formation and three D- newborns with RHD*09.01 and RHD*09.03.01 variants, potentially capable of inducing anti-D. CONCLUSION: RHD variants at risk for anti-D are common among serologic D- individuals from African descent in Suriname. While genotyping D- women has limited added value, it may be considered in newborns from D- women.

Prevalence of positive direct antiglobulin test and clinical outcomes in Surinamese newborns from D-negative women.

BACKGROUND: In low-resource countries, screening for D antibodies to detect pregnancies at risk for hemolytic disease of the newborn is not routine practice. Retrospective data showed that 5.5% of Surinamese newborns of D-negative women had a positive direct antiglobulin test (DAT), indicating the presence of maternal antibodies against fetal antigens. Here, the frequency and clinical relevance of DAT positivity is evaluated. STUDY DESIGN AND METHODS: Between April 2015 and June 2016, an observational, multicenter cohort study was undertaken among Surinamese newborns born to D-negative women. In newborns, the DAT was performed, and clinical outcomes between DAT-negative and DAT-positive newborns were compared. RESULTS: Of the 232 evaluable newborns, 19 (8.2%) had a positive DAT, of which 11 of 15 antibody-tested newborns had D antibodies. DAT-positive newborns had lower hemoglobin levels (p = 0.02) and a trend toward higher bilirubin concentrations (p = 0.09) in the first days of life compared with DAT-negative newborns. DAT-positive newborns were admitted more frequently (p = 0.02), needed phototherapy treatment almost four times as often as DAT-negative newborns (26% vs. 7%; p = 0.008), and therapy took 2 days longer (p = 0.01). Exchange transfusions were performed in two newborns with D antibodies, both complicated with sepsis. The hospital stay was 2.5 days longer for DAT-positive newborns (p = 0.007). Overall, the prevalence of hemolytic disease of the newborn requiring treatment was 2.2% among the whole cohort of newborns. CONCLUSION: We found a high prevalence of DAT positivity with substantial need for hyperbilirubinemia treatment in newborns in Suriname. These results stress the necessity for better management procedures in D-negative women.

D antibodies in pregnant women in multiethnic Suriname: the observational RheSuN study.

BACKGROUND: Maternal antibodies against the D antigen are the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). In high-income countries, the risk of D immunization has been reduced by routine antenatal and postpartum administration of RhIG from 13% to less than 0.5%. In less-resourced countries, such as Suriname, red blood cell (RBC) antibody screening during pregnancy and prophylactic RhIG administration are not routine. Accurate data on D immunization risk is not available. In the RheSuN (Rhesus Surinamese Neonates) study, the prevalence and the hemolytic potential of maternal D antibodies were investigated. STUDY DESIGN AND METHODS: A multicenter cross-sectional study in four major hospitals in Paramaribo, Suriname, covering 90% of approximately 10,000 births yearly in Suriname. Included were D- pregnant women of various ethnicities seeking routine prenatal care and/or their newborns. RESULTS: D antibodies were detected in 19 of 214 D- pregnancies (8.9%; 95% confidence interval, 5.1%-12.7%), in 2.0% of primigravid and 11.7% of multigravid women. The direct antiglobulin test was positive in 11 of 13 tested D+ newborns. Determination of D antibody titers and antibody-dependent cell mediated cytotoxicity (ADCC) assay revealed three newborns at high risk for HDFN (ADCC > 50%). CONCLUSION: D immunization risk in Suriname women is comparable to the pre-anti-D prophylaxis era in high-income countries. Recommended is free-of-charge routine RBC antibody screening and prophylactic RhIG administration for women at risk for D antibody formation as part of standard of ante- and postnatal care.

Blood Group Antigen Matching Influence on Gestational Outcomes (AMIGO) study.

BACKGROUND: Red blood cell (RBC) antigen matching policies to prevent alloimmunization in females of childbearing potential (FCP) vary between centers. To inform transfusion centers responsible for making decisions about matching policies for FCPs, the causal stimulus of the antibodies implicated in severe hemolytic disease of the fetus and newborn (HDFN) must be determined. STUDY DESIGN AND METHODS: We conducted a multinational retrospective study of women with offspring affected by severe HDFN requiring neonatal exchange transfusion and/or intrauterine transfusion. Mothers treated at centers that provide extended antigen-negative RBCs (MATCH, five centers) and those that do not (NoMATCH, nine centers) were compared. RESULTS: A total of 293 mothers had at least one affected pregnancy: 179 at MATCH centers and 114 at NoMATCH centers. Most alloimmunization (83%) was attributed to previous pregnancy: 3% to transfusion (two cases at MATCH, six at NoMATCH centers) and 14% undetermined (both antecedent transfusion and pregnancy). Only 50 mothers had received transfusions; 13 had HDFN due to anti-K at MATCH and four at NoMATCH centers. Most (12/13, 92%) of the anti-K HDFN cases at MATCH centers had K+ paternal antigen status. Mothers at the MATCH centers do not appear to be protected from HDFN due to K, C, c, and E antibodies, although the low number of FCPs who received transfusions precluded drawing firm conclusions. CONCLUSION: The causal stimulus of antibodies that cause HDFN is predominantly from previous pregnancy. Although extended RBC matching for FCPs may impart some protection from allosensitization, we were unable to show a positive effect, possibly because matching policies are not uniform and there was a small number of mothers who previously received transfusions.

Incidence of alloantibody formation after ABO-D or extended matched red blood cell transfusions: a randomized trial (MATCH study).

BACKGROUND: Most incidentally transfused patients receive only ABO-D-compatible transfusions and antibodies are formed in up to 8%. The effect of extended (c, C, E, K, Fy(a) , Jk(a) , and S antigens) matched (EM) and ABO-D-matched red blood cell (RBC) transfusions on the incidence of new clinically relevant RBC antibody formation after a first elective transfusion event in surgical patients was studied. STUDY DESIGN AND METHODS: A multicenter randomized trial was performed in nontransfused patients who were scheduled to experience a single elective transfusion event of maximal 4 RBC units. The primary outcome was the incidence of newly formed warm reacting clinically relevant RBC alloantibodies measured in three follow-up (FU) samples taken at 7 to 10 days, 4 to 6 weeks, and 4 to 6 months posttransfusion. RESULTS: A total of 853 patients were randomized, and of these, 333 patients were transfused with a total of 1035 RBC units. At least one FU sample was available from 97% of transfused patients. In intention-to-treat analysis, new antibodies were detected in 10 of 155 ABO-D and seven of 178 EM patients, respectively. Per-protocol analysis including 190 patients showed a nonsignificant absolute risk difference (ARD) of 5.3% (95% confidence interval [CI], -1.4% to 12%) in alloimmunization between study arms. In a post hoc analysis of 138 patients who received RBCs but no platelet (PLT) transfusions the ARD increased to significance, 8.0% (95% CI, 0.4-16.0). CONCLUSION: Extended matching for selected antigens reduced the alloimmunization risk by 64% in surgical patients. Extended matching seems successful only if the patient did not receive accompanying nonmatched PLT transfusions.

The HLA-DRB1*15 phenotype is associated with multiple red blood cell and HLA antibody responsiveness.

BACKGROUND: Once a patient has produced a red blood cell (RBC) antibody, there is an increased risk of additional antibody formation after subsequent RBC exposure. Recently, we observed that HLA-DRB1*15 was overrepresented in 379 multiple RBC antibody responders compared to controls or 562 patients with a single RBC antibody (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3-2.3). In this study we evaluated whether the HLA-DRB1*15 represents a responder phenotype against HLA and/or RBC antigens. STUDY DESIGN AND METHODS: HLA-DRB1*15 frequencies in single and multiple antibody responders were compared between three groups of individuals: 1) those with HLA antibodies, 2) those with RBC antibodies, and 3) those with both RBC and HLA antibodies. RESULTS: A total of 3959 immunized patients (female-to-male ratio, 2.3) had been HLA-DRB1 typed. Among the 3275 individuals with HLA antibodies, the frequency of the DRB1*15 phenotype differed significantly from 19.7% in patients with a panel reactivity (PRA) of not more than 20% to 26.9% in patients with PRA of more than 80% (OR, 1.5; 95% CI, 1.2-1.9). This association between DRB1*15 and multiresponsiveness was mainly due to pregnancy-induced HLA immunization. In the 257 individuals with RBC and HLA antibodies, the frequency of DRB1*15 was 4.2 times (95% CI, 1.1-16) higher in those with multiple RBC antibodies and HLA-PRA of more than 50% compared to only single RBC responders with PRA of less than 20%. CONCLUSION: The HLA-DRB1*15 phenotype is associated with broad RBC and HLA immunization.

Factors associated with persistence of red blood cell antibodies in woman after pregnancies complicated by fetal alloimmune haemolytic disease treated with intrauterine transfusions.

Red blood cell (RBC) antibodies can persist for decades or decrease quickly to undetectable levels. Antibody persistence has not been systematically studied. Women whose children are treated with intrauterine transfusions (IUT) for haemolytic disease of the fetus (HDFN) often produce additional antibodies, which can be evoked by the intrauterine transfusion or by fetomaternal haemorrhage during the procedure. Factors associated with persistence of both the antibodies responsible for HDFN and additional antibodies were studied in 260 women whose children were treated with IUT between 1988 and 2008. They possessed 499 (205 anti-D and 294 non-D) antibodies after the last IUT. After a median follow-up of 8·7 years, all 260 antibodies primarily responsible for HDFN had persisted. Additional antibodies directed against antigens of the children persisted in 70·6%, and in 32·3% if they were not child-specific (P < 0·001). Antibodies induced by irradiated IUT persisted in only 7·1%. Multivariate analyses showed that non-HDFN antibody persistence was dependent on the antibody titre and specificity. In conclusion, persistence of antibodies mainly depends on antibody strength and specificity. Difference between fetal or non-fetal immunogens suggests maintenance of antigenic stimulation possibly by long-term fetomaternal chimerism.

Health-Related Quality of Life and Behavioral Functioning after Intrauterine Transfusion for Alloimmune Anemia.

OBJECTIVE: To assess health-related quality of life (HRQOL) and behavioral functioning in children and adolescents treated before birth with intrauterine intravascular blood transfusion for alloimmune anemia. STUDY DESIGN: Cross-sectional cohort study conducted at the Dutch referral center for the management of fetal alloimmune anemia. Follow-up data were available for 285 children at a mean age of 10.5 years (range, 3-21.5 years) with a response rate for questionnaires of 97%. Child-, adolescent-, and parent-rated HRQOL was evaluated with The Netherlands Organization for Applied Scientific Research Child/Adult Quality of Life Questionnaire (TACQOL/TAAQOL). Parents reported on behavioral functioning with the Strengths and Difficulties Questionnaire. Scores were compared with Dutch norm data. RESULTS: Significantly lower scores were reported by parents of children 6-11 years of age compared with Dutch norms on 3 scales: cognitive functioning, social functioning, and positive emotions (P < .00, P = .02, and P = .04). In children aged 8-11 years only the cognitive functioning scale score was significantly lower compared with Dutch norms (P = .01). The children aged 12-15 years reported higher scores on the negative emotions scale (P = .02). When corrected for multiple testing, only the parent-rated cognitive functioning scale remained significant (P < .001). Regarding the HRQOL scores of adolescents aged ≥16 years, no differences were detected. Overall, behavioral difficulties were reported in 37/246 (15%) children aged 3-16 years, and were associated with maternal educational levels (P < .001). CONCLUSION: Parents reported lower scores on cognitive functioning in their children aged 6-11 years compared with norms. Behavioral difficulties were more prevalent than norms, and were associated with maternal educational level. Outcomes of children after intrauterine intravascular blood transfusion were quite good overall.

Female sex of older patients is an independent risk factor for red blood cell alloimmunization after transfusion.

BACKGROUND: More women than men are encountered with red blood cell (RBC) antibodies. It is not clear whether this difference is explained by more immunizing events in women or by a different acting immune system. To assess whether there is a difference in the posttransfusion RBC alloimmunization rate between women and men, a study on RBC alloimmunization during a 5-year period was conducted in patients with at least one antibody follow-up more than 14 days after transfusion. STUDY DESIGN AND METHODS: Data on transfusion and antibody follow-up characteristics in female and male transfusion recipients from the Leiden University Medical Center laboratory database were collected. Hazard ratios of alloimmunization, according to sex of the transfusion recipient, were estimated using Cox proportional hazards regression models taking possible confounders into account. RESULTS: From a total of 1699 women and 1969 men who were eligible, 4.2% of women and 3.4% of men (relative risk, 1.3; 95% confidence interval [CI], 0.9-1.8) developed posttransfusion antibodies. Adjustment for confounders resulted in a relative 80% higher risk in women older than 45 years of age. CONCLUSION: Elder women beyond childbearing age have a higher risk of posttransfusion antibody formation compared to men.

Anti-K formation is not associated with the storage time of transfused red blood cells.

BACKGROUND: The formation of red blood cell (RBC) antibodies could be enhanced by the presence of inflammation caused by prolonged RBC storage, as was shown in animal studies. The low occurrence (<10%) of K-antigen in most populations often enables identification of the K+ RBC unit that triggered anti-K formation and determination of its storage time. This study aims to quantify the association of anti-K formation with RBC storage time. STUDY DESIGN AND METHODS: K- patients who had not been previously transfused and received at least 1 K+ unit between January 2004 and August 2013 were identified. First, the influence of storage time of the K+ units was assessed as mean, maximum, and minimum storage times within one transfusion interval and at various cutoff points for old versus young blood (14, 18, and 21 days). Second, concomitantly transfused K- units were studied within different periods surrounding the K+ unit(s). RESULTS: Twenty-three patients formed anti-K, while 274 patients did not. The adjusted relative risks of anti-K formation for mean, maximum, and minimum storage time (days) ranged from 1.01 to 1.03 (95% confidence interval, 0.96-1.08). When analyzing the association between only "younger" and only "older" K+ units at various cutoff points, no association was found. Similarly, no association was found between storage time of the concomitantly transfused K- units and anti-K formation. CONCLUSION: Within the range of storage times used in normal clinical practice in the Netherlands, no association could be found between RBC storage time and anti-K formation.

A new preparation method for red blood cells for intrauterine transfusion enabling reduction of donor exposure.

BACKGROUND: Severe hemolytic anemia of the fetus, caused by maternal red blood cell (RBC) alloantibodies, is treated with intrauterine transfusion (IUT) of RBCs. Because IUT is associated with additional antibody formation, RBCs with the closest match between donor and mother are preferred. Because one fetus needs a median of three IUTs, finding such RBCs is complicated. Collection of repeated low-volume donations from one selected donor during the entire IUT treatment period would reduce donor exposure and possibly IUT-associated alloimmunization. STUDY DESIGN AND METHODS: Whole blood (WB) donations of 100 and 200 mL were diluted with saline, filtered, centrifuged, and separated to prepare experimental RBCs. Before and after gamma irradiation, the RBCs were sampled for comparison of in vitro quality with standard RBCs for IUT. An additional washing procedure was investigated to remove anti-A/-B. RESULTS: Experimental RBCs were leukoreduced to levels conforming with current guidelines and had final volumes of 44 (n = 12) and 84 (n = 8) mL with hematocrit levels between 0.80 and 0.88 L/L. Hemolysis was lower (0.12% vs. 0.42%), potassium leakage comparable, adenosine triphosphate levels lower (4.8 µmol/g Hb vs. 6.1 µmol/g Hb), and 2,3-diphosphoglycerate levels higher (10.3 µmol/g Hb vs 7.7 µmol/g Hb) at 6 hours after irradiation (product expiration time) compared to standard RBCs for IUT (n = 3). Anti-A/-B titers decreased substantially by the washing procedure. CONCLUSION: RBCs for IUT can be prepared from 100- or 200-mL WB donations, showing the potential of this new blood product to reduce donor exposure. A washing procedure is recommended to remove anti-A/-B.

Extended matched intrauterine transfusions reduce maternal Duffy, Kidd, and S antibody formation.

BACKGROUND: Severe alloimmune hemolytic disease of the fetus is treated with intrauterine transfusions (IUTs). Despite C, c, E, e, and K matching between mother and donor, IUT results in new antibodies in approximately 25% of women. Newly formed Fy(a), Fy(b), Jk(a), Jk(b), and S antibodies are in 83% presumably induced by the IUT donor. Therefore, we intentionally extended matching between mother and IUT donor for these additional antigens. The results, after almost 8 years of applying this protocol, are reported. STUDY DESIGN AND METHODS: Data from February 2007 to August 2014 on IUT patients were retrieved from the Leiden University Medical Center database and from donors from the Sanquin National Donor Database. Maternal data included red blood cell (RBC) antigen profiles, RBC antibodies, and date and consecutive number of each IUT. From the fathers, children, and IUT donors the RBC antigen profiles were retrieved. RESULTS: A total of 182 fetuses from 159 women were treated with 481 IUTs. Of these, 317 IUTs (66%) were matched for Duffy, Kidd, and S antigens. Only matched IUTs were received by 77 women (48%) and 82 (52%) received (partly) nonmatched IUTs. Evaluable for new antibodies were 142 women. Duffy, Kidd, or S antibodies were formed by three of 69 women (4.3%) after matched IUTs and by eight of 73 women (11.0%) after nonmatched IUTs. CONCLUSION: Extended matching for all IUTs was not possible for approximately 50% of women. Strict adherence to Duffy, Kidd, and S antigens-matched IUTs decreased immunization against these antigens by 60% compared to nonmatched IUTs.