Estimating the serological underrecognition of patients with weak or partial RHD variants.

BACKGROUND: For patients with weak or discrepant RhD RBC phenotypes, RHD genotyping is employed to determine need for RhD-negative management. However, many RHD variants are type D-negative or D-positive. Serological recognition rates (RRs) of weak and partial RHD variants are poorly characterized. STUDY DESIGN AND METHODS: Four US studies employing RHD genotyping for weak or discrepant RhD phenotypes provided data for race/ethnicity-specific serological recognition. Three studies used microplate, and 1 used gel and tube; 2 had anti-D data. We obtained White and Hispanic/Latino allele frequencies (AFs) of weak D types 1, 2, and 3 single-nucleotide variants (SNVs) from the Genome Aggregation Database (gnomAD, v4.0.0) and devised Hardy-Weinberg-based formulas to correct for gnomAD's overcount of hemizygous RHD SNVs as homozygous. We compiled common partial RHD AF from genotyped cohorts of US Black or sickle cell disease subjects. From variant AF, we calculated hemizygous-plus-homozygous genetic prevalences. Serological prevalence: genetic prevalence ratios yielded serological RRs. RESULTS: Overall RRs of weak D types 1-3 were 17% (95% confidence interval 12%-24%) in Whites and 12% (5%-27%) in Hispanics/Latinos. For eight partial RHD variants in Blacks, overall RR was 11% (8%-14%). However, DAR RR was 80% (38%-156%). Compared to microplate, gel-tube recognition was higher for type 2 and DAU5 and lower for type 4.0. Anti-D was present in 6% of recognized partial RHD cases, but only in 0.7% of estimated total genetic cases. DISCUSSION: Based on AF, >80% of patients with weak or partial RHD variants were unrecognized serologically. Although overall anti-D rates were low, better detection of partial RHD variants is desirable.

Transfusion-Transmitted Cache Valley Virus Infection in a Kidney Transplant Recipient With Meningoencephalitis.

BACKGROUND: Cache Valley virus (CVV) is a mosquito-borne virus that is a rare cause of disease in humans. In the fall of 2020, a patient developed encephalitis 6 weeks following kidney transplantation and receipt of multiple blood transfusions. METHODS: After ruling out more common etiologies, metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) was performed. We reviewed the medical histories of the index kidney recipient, organ donor, and recipients of other organs from the same donor and conducted a blood traceback investigation to evaluate blood transfusion as a possible source of infection in the kidney recipient. We tested patient specimens using reverse-transcription polymerase chain reaction (RT-PCR), the plaque reduction neutralization test, cell culture, and whole-genome sequencing. RESULTS: CVV was detected in CSF from the index patient by mNGS, and this result was confirmed by RT-PCR, viral culture, and additional whole-genome sequencing. The organ donor and other organ recipients had no evidence of infection with CVV by molecular or serologic testing. Neutralizing antibodies against CVV were detected in serum from a donor of red blood cells received by the index patient immediately prior to transplant. CVV neutralizing antibodies were also detected in serum from a patient who received the co-component plasma from the same blood donation. CONCLUSIONS: Our investigation demonstrates probable CVV transmission through blood transfusion. Clinicians should consider arboviral infections in unexplained meningoencephalitis after blood transfusion or organ transplantation. The use of mNGS might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients.

International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn.

Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.

RHD genotyping to resolve weak and discrepant RhD patient phenotypes.

BACKGROUND: We instituted RHD genotyping in our transfusion service for obstetrical patients and transfusion candidates. We sought to examine how RHD genotyping resolved weak or discrepant automated microplate direct agglutination (MDA) RhD phenotypings and impacted needs for Rh Immune Globulin (RhIG) and D-negative RBCs. STUDY DESIGN AND METHODS: We investigated RhD phenotypes with equivocal or reagent-discrepant automated MDA (Immucor, Norcross, GA), weak-2+ immediate-spin tube typings, historically discrepant RhD typings, or D+ typings with anti-D. We performed microarray RHD genotyping (RHD BeadChip, Immucor BioArray Solutions, Warren, NJ). Patients were managed as D+ with weak-D types 1, 2, and 3, and as D-negative with all other results. RESULTS: Our weak-D prevalence was 0.14%. Among 138 patients (73 obstetrics, 65 transfusion candidates), 38% had weak-D types 1, 2 or 3, 25% weak partial type 4.0, 21% other partial-D variant alleles, and 15% no variant detected. One novel allele with weak partial type 4.0 variants plus c.150T>C (Val50Val) was discovered. Weak D types 1, 2 or 3 were identified in 66% (48/73) of Whites versus 3% (2/62) of diverse ethnic patients (p < .0001). RHD genotyping changed RhD management in 60 patients (43%) (49 to D+, 11 to D-negative), resulting in net conservation of D-negative RBCs (98 avoided, 14 given) and RhIG (8 avoided, 3 given). CONCLUSION: In our patient population, equivocal or reagent-discrepant MDA RhD phenotypes were highly specific for weak-D or partial-D RHD genotypes. Resolution of RHD genotype status reduced our use of D-negative RBCs and RhIG.

Passive Immunity for Coronavirus Disease 2019: A Commentary on Therapeutic Aspects Including Convalescent Plasma.

In the ongoing pandemic of coronavirus disease 2019 (COVID-19), the novel virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is infecting a naïve population. The innate immunity of the infected patient is unable to mount an effective defense, resulting in a severe illness with substantial morbidity and mortality. As most treatment modalities including antivirals and anti-inflammatory agents are mostly ineffective, an immunological approach is needed. The mechanism of innate immunity to this viral illness is not fully understood. Passive immunity becomes an important avenue for the management of these patients. In this article, the immune responses of COVID-19 patients are reviewed. As SARS-CoV-2 has many characteristics in common with two other viruses, SARS-CoV that cause severe acute respiratory syndrome (SARS) and MERS-CoV (Middle East respiratory syndrome coronavirus) that causes Middle East respiratory syndrome (MERS), the experiences learned from the use of passive immunity in treatment can be applied to COVID-19. The immune response includes the appearance of immunoglobulin M followed by immunoglobulin G and neutralizing antibodies. Convalescent plasma obtained from patients recovered from the illness with high titers of neutralizing antibodies was successful in treating many COVID-19 patients. The factors that determine responses as compared with those seen in SARS and MERS are also reviewed. As there are no approved vaccines against all three viruses, it remains a challenge in the ongoing development for an effective vaccine for COVID-19.

Blood transfusion utilization in hospitalized COVID-19 patients.

BACKGROUND: The acute respiratory illness designated coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, in December 2019 and caused a worldwide pandemic. Concerns arose about the impact of the COVID-19 pandemic on blood donations and potential significant blood transfusion needs in severely ill COVID-19 patients. Data on blood usage in hospitalized COVID-19 patients are scarce. STUDY DESIGN AND METHODS: We performed a retrospective observational study of blood component transfusions in the first 4 weeks of COVID-19 ward admissions. The study period began 14 days before the first COVID-19 cohort wards opened in our hospital in March 2020 and ended 28 days afterward. The number of patients and blood components transfused in the COVID-19 wards was tabulated. Transfusion rates of each blood component were compared in COVID-19 wards versus all other inpatient wards. RESULTS: COVID-19 wards opened with seven suspected patients and after 4 weeks had 305 cumulative COVID-19 admissions. Forty-one of 305 hospitalized COVID-19 patients (13.4%) received transfusions with 11.1% receiving red blood cells (RBCs), 1.6% platelets (PLTs), 1.0% plasma, and 1.0% cryoprecipitate (cryo). COVID-19 wards had significantly lower transfusion rates compared to non-COVID wards for RBCs (0.03 vs 0.08 units/patient-day), PLTs (0.003 vs 0.033), and plasma (0.002 vs 0.018; all p < 0.0001). Cryo rates were similar (0.008 vs 0.009, p = 0.6). CONCLUSIONS: Hospitalized COVID-19 patients required many fewer blood transfusions than other hospitalized patients. COVID-19 transfusion data will inform planning and preparation of blood resource utilization during the pandemic.

Blood transfusions in mass casualty events: recent trends.

BACKGROUND AND OBJECTIVES: The US AABB disaster task force recommends estimating 3 RBC units per admission (UPA) for mass casualty events (MCEs). In a previous analysis, median MCE UPA were 2·7 RBCs, 1·2 plasmas and 0·27 platelet doses (Vox Sang 2017; 112:648). Additional recent data were sought from the current era of balanced massive transfusion protocols (bMTPs). MATERIALS AND METHODS: Publications in English from 1980 to 2020 were reviewed for MCEs using ≥50 RBCs/event and with numbers of admissions available. MCE reports were stratified by era and event-wide or trauma-centre source. The bMTP era included all MCEs since 2010 plus a 2008 bMTP military report. STATISTICS: Mann-Whitney test. RESULTS: Thirty-two MCEs met analysis criteria. Event-wide reports used medians [interquartile ranges] of 1·8 [1·2-3·9] RBC, 0·6 [0·3-0·9] plasma and 0·14 [0·06-0·26] platelet-dose UPA. Trauma centres transfused 3·4 [2·7-6·3] RBC, 2·4 [1·3-4·1] plasma and 0·41 [0·34-0·50] platelet-dose UPA, all P < 0·05 vs event-wide. Same-event median post-day-1 transfusions were 50% of day-1 use for RBC, 28% for plasma and 16% for platelets. Compared to prior years, the median plasma/RBC transfusion ratio rose from 0·28 to 0·67 in the bMTP era (P < 0·01). In recent mass shootings, trauma centres transfused up to 42 platelets (range 0·45-0·57 UPA) on day 1. CONCLUSION: Based on available mass casualty data, we recommend planning for 3 RBC, 1 plasma and one-fourth platelet-dose units per admission for blood centres (event-wide), and 6, 4 and one-half UPA, respectively, for trauma centres, which have seen rising plasma usage and large mass-shooting platelet needs.

Thrombosis Risk in Cancer Patients Receiving Red Blood Cell Transfusions.

Patients with cancer have increased risk of thrombosis and often need red blood cell (RBC) transfusions. However, RBC transfusions may also promote thrombosis because of raised hematocrit and viscosity, storage-related RBC damage, and exposure to thrombogenic mediators from obsolescent RBCs. The authors conducted a literature survey for studies examining whether RBC transfusions were associated with increased risk of venous thromboembolism (VTE) in cancer patients. In perioperative cancer surgery patients with categorical comparisons of any versus no RBC transfusion, increased risk of VTE with RBC transfusion was found in 11 of 31 studies, 5 by univariate correlation only and 6 in multivariate analysis. All six multivariate-positive studies had intermediate overall rates of thrombosis (1.4-6.0%), and three were in urological surgery series. In the larger studies of > 2,000 patients (range: 2,219-44,656), the maximum odds ratio among the multivariate-positive studies was 1.3. Perioperative RBC transfusion volume was more strongly associated with VTE risk, with a positive association in six of seven studies. One large registry-based study of hospitalized cancer patients, not restricted to the perioperative setting, found an adjusted odds ratio of 1.60 (95% confidence interval: 1.53-1.67) for VTE risk in patients receiving RBCs compared with nontransfused patients.

Critical developments of 2018: A review of the literature from selected topics in transfusion. A committee report from the AABB's Clinical Transfusion Medicine Committee.

BACKGROUND: The AABB compiles an annual synopsis of the published literature covering important developments in the field of transfusion medicine. An abridged version of this work is being made available in TRANSFUSION, with the full-length report available as Appendix S1 (available as supporting information in the online version of this paper). STUDY DESIGN AND METHODS: Papers published in late 2017 and 2018 are included, as well as earlier papers cited for background. Although this synopsis is comprehensive, it is not exhaustive, and some papers may have been excluded or missed. RESULTS: The following topics are covered: "big data" and "omics" studies, emerging infections and testing, platelet transfusion and pathogen reduction, transfusion therapy and coagulation, transfusion approach to hemorrhagic shock and mass casualties, therapeutic apheresis, and chimeric antigen receptor T-cell therapy. CONCLUSION: This synopsis may be a useful educational tool.

Critical developments of 2017: a review of the literature from selected topics in transfusion. A committee report from the AABB Clinical Transfusion Medicine Committee.

BACKGROUND: The AABB compiles an annual synopsis of the published literature covering important developments in the field of Transfusion Medicine. For the first time, an abridged version of this work is being made available in TRANSFUSION, with the full-length report available as an Appendix S1 (available as supporting information in the online version of this paper). STUDY DESIGN AND METHODS: Papers published in 2016 and early 2017 are included, as well as earlier papers cited for background. Although this synopsis is comprehensive, it is not exhaustive, and some papers may have been excluded or missed. RESULTS: The following topics are covered: duration of red blood cell storage and clinical outcomes, blood donor characteristics and patient outcomes, reversal of bleeding in hemophilia and for patients on direct oral anticoagulants, transfusion approach to hemorrhagic shock, pathogen inactivation, pediatric transfusion medicine, therapeutic apheresis, and extracorporeal support. CONCLUSION: This synopsis may be a useful educational tool.

Hemostatic Efficacy of Pathogen-Inactivated Blood Components.

Pathogen inactivation (PI), or pathogen reduction technology, reduces the infectious risk of plasma and platelet transfusions, and also affects clotting factor activities and platelet viabilities. Plasma is treated with solvent-detergent to disrupt enveloped viruses, or with photoactive agents methylene blue plus light, or amotosalen (AM) or riboflavin (RF) plus ultraviolet (UV) light, to disrupt pathogen nucleic acids. PI plasmas have average clotting factor activities of 75 to 85% of untreated plasma. PI plasmas are generally equivalent to regular plasma in randomized clinical trials (RCTs) in regard to coagulation test corrections and bleeding outcomes, except for one trial in which RF plasma was inferior for prothrombin time correction. Platelets are treated with UV plus RF or AM. In RCTs, the mean 1-hour corrected count increments from PI platelets are 66 to 94% (trials median, 75%) of those from untreated platelets. PI platelets also have lifespans of 4 to 5 days after 5 days of storage, compared with 6 to 7 days for untreated platelets. Bleeding outcomes comparing PI versus non-PI platelets in RCTs have been equivalent, except one study with more bleeding on AM platelets. Platelet treatment with UVC light alone for PI has entered clinical trials.

A Caucasian JK*A/JK*B woman with Jk(a+b-) red blood cells, anti-Jkb, and a novel JK*B allele c.1038delG.

The Kidd blood group on the red blood cell (RBC) glycoprotein urea transporter-B has a growing number of weak and null alleles in its gene SLC14A1 that are emerging from more widespread genotyping of blood donors and patients. We investigated a 64-year-old Caucasian woman of Polish-Czech descent who developed anti-Jkb detected in solid-phase RBC adherence testing within 12 days after 7 units of RBCs were transfused. Her RBCs subsequently typed Jk(a+b­) by licensed reagents and human antisera. Nevertheless, in RBC genotyping (BioArray HEA BeadChip, Immucor, Warren, NJ) performed in our transfusion service on all patients with alloantibodies, her Kidd typing was JK*A/JK*B based on the Jka/Jkb single nucleotide polymorphism in exon 9 (c.838G>A, p.Asp280Asn). Genomic analysis and cDNA sequencing of her JK*B allele revealed a novel single-nucleotide deletion of c.1038G in exon 11, predicting a frameshift and premature stop (p.Thr346Thrfs*5) after translation of nearly 90 percent of the expressed exons 4­11. This allele has been provisionally named JK*02N.14, subject to approval by the International Society of Blood Transfusion Working Party. The site of this variant is closer to the C-terminus than that of any allele associated with the Jk(a­b­) phenotype reported to date. Routine genotyping of patients with RBC alloantibodies can reveal variants posing potential risk of alloimmunization. Continuing investigation of Kidd variants may shed light on the structure of Kidd antigens and the function of urea transporter-B.

Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage.

Importance: More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. Objective: To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Evidence Review: Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. Findings: It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence). Conclusions and Relevance: Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.

Characterising the challenges of managing difficult red blood cell alloantibodies in liver transplant recipients.

AIMS: Formation of red blood cell alloantibodies (RBCAs) complicates transfusion support in liver transplantation (LT). Difficult RBCAs (DAs, >3 antibodies or antibodies for which <25% donors are antigen negative) further challenge care. This study characterises DA outcomes relative to non-difficult RBCAs (NDAs). METHODS: Single-centre, retrospective analysis of LT patients (2002-2021). RBCAs were defined as clinically significant antibodies. DAs were compared with NDAs. RESULTS: 89 patients had clinically significant RBCAs (DA=50, NDA=39). More DAs were anti-Jka, anti-M; fewer were anti-E, anti-K (all p<0.05). DA patients often had multiple antibodies (44% vs 12.8% NDA, p=0.0022). Probability of finding antigen-negative blood was lower for DAs (17.4% vs 68.1% NDA, p<0.0001) as was RBCs received (9.4 vs 14.7 units in NDA, p=0.0036). Although survival was similar, patients with DAs had more adverse reactions (8% vs 0%, p=0.128). Some antibodies appeared to occur with specific liver diseases (such as primary sclerosing cholangitis, alcoholic steatohepatitis and recurrent disease); however, due to low sample size, definitive conclusions cannot be made. CONCLUSIONS: DA LT recipients contain >1 RBCA, have a lower probability of finding antigen negative blood and may experience more adverse transfusion event (ATE). Despite this, the incidence of ATEs was still quite low.

Alloimmunization in sickle cell anemia in the era of extended red cell typing.

BACKGROUND: Red blood cell (RBC) transfusion remains an essential part of the management of patients with sickle cell disease (SCD). Alloimmunization is a major complication of transfusions. Extended RBC typing is advocated as a means to reduce alloimmunization in SCD. Our goal was to assess alloimmunization among individuals with SCD at our center since implementing extended RBC typing. MATERIALS AND METHODS: We reviewed electronic medical records of all patients with SCD (N = 641) in our comprehensive SCD Program to determine transfusion histories. Cross-referencing with our blood bank database, we extracted data such as antibodies identified, detection date and genotyping in specific cases. Transfusion sources were determined for those with C, E, and Kell antibodies. RESULTS: Of 180 patients transfused from 2002 to 2011, 26 developed at least one new antibody. The majority of alloimmunized patients (14/26) received episodic transfusions only. The most common antibodies formed were against C and E antigens. Of the 16 patients who developed C, E, Kell antibodies, nine had one or more documented transfusions at an outside hospital. Five patients had Rh variants undetectable on routine phenotyping including two novel e alleles related to ceAR and ce(S)(733G). CONCLUSION: Despite extended RBC typing, alloimmunization may still occur due to RBC variants that are not detected on routine screening and transfusions at institutions where extended RBC typing is not done. Extended RBC typing should be the standard of care for patients with SCD. Prospective genotyping may reduce allosensitization to rare variants not detected on routine screening.

Alloimmunization Against RBC Antigens Is Not Associated With Decreased Survival in Liver Transplant Recipients.

BACKGROUND: Improvement of liver transplantation (LT) outcomes requires better understanding of factors affecting survival. The presence of RBC alloantibodies (RBCAs) on survival in LT recipients was evaluated. METHODS: This study was a single-center, retrospective cohort study reviewing transfusion records and all-cause mortality between 2002 and 2021. RESULTS: Between 2002 and 2021, 2079 LTs were completed, 1,396 of which met inclusion criteria (1,305 RBCA negative; 91 RBCA positive [6.5%]). The cohorts were similar in age (mean [range], 55.8 [17-79] years vs 56.8 [25-73] years; P = .41, respectively) or sex (RBCA negative, 859 [65%] men and 446 [35%] women vs RBCA positive, 51 [56%] men and 40 [44%] women; P = .0684). Of 132 RBCAs detected, 10 were most common were to E (27.27%), Jka (15.91%), K (9.09%), C (8.33%), M (6.06%), D (5.3%), Fya (4.55%), e (2.27%), c (2.27%), and Jkb (2.27%). Twenty-seven patients (29.7%) had more than 1 RBCA; the most common combinations were C with Jka (7.4%) and E with Dia (7.4%). All-cause mortality was increased in men (men, 14.45 years vs women, 17.27 years; P = .0266) and patients 65 years of age and older (≥65 years of age, 10.21 years vs <64 years of age, 17.22 years; P < .0001). The presence of RBCA (≥1) did not affect all-cause mortality (RBCA negative, 14.17 years vs RBCA positive, 15.29 years; P = .4367). The top 5 causes of death were infection (11.9%), primary malignancy (solid) (10.8%), recurrent malignancy (10.5%), cardiovascular arrest (7.1%), and pulmonary insufficiency/respiratory failure (5.7%). CONCLUSIONS: Survival in RBCA-positive LT recipients is no different from that in RBCA-negative LT recipients.

Obstetric and Newborn Weak D-Phenotype RBC Testing and Rh Immune Globulin Management Recommendations: Lessons From a Blinded Specimen-Testing Survey of 81 Transfusion Services.

CONTEXT.­: Modern RHD genotyping can be used to determine when patients with serologic weak D phenotypes have RHD gene variants at risk for anti-D alloimmunization. However, serologic testing, RhD interpretations, and laboratory management of these patients are quite variable. OBJECTIVE.­: To obtain interlaboratory comparisons of serologic testing, RhD interpretations, Rh immune globulin (RhIG) management, fetomaternal hemorrhage testing, and RHD genotyping for weak D-reactive specimens. DESIGN.­: We devised an educational exercise in which 81 transfusion services supporting obstetrics performed tube-method RhD typing on 2 unknown red blood cell challenge specimens identified as (1) maternal and (2) newborn. Both specimens were from the same weak D-reactive donor. The exercise revealed how participants responded to these different clinical situations. RESULTS.­: Of reporting laboratories, 14% (11 of 80) obtained discrepant immediate-spin reactions on the 2 specimens. Nine different reporting terms were used to interpret weak D-reactive maternal RhD types to obstetricians. In laboratories obtaining negative maternal immediate-spin reactions, 28% (16 of 57) performed unwarranted antiglobulin testing, sometimes leading to recommendations against giving RhIG. To screen for excess fetomaternal hemorrhage after a weak D-reactive newborn, 47% (34 of 73) of reporting laboratories would have employed a contraindicated fetal rosette test, risking false-negative results and inadequate RhIG coverage. Sixty percent (44 of 73) of laboratories would obtain RHD genotyping in some or all cases. CONCLUSIONS.­: For obstetric and neonatal patients with serologic weak D phenotypes, we found several critical problems in transfusion service laboratory practices. We provide recommendations for appropriate testing, consistent immunohematologic terminology, and RHD genotype-guided management of Rh immune globulin therapy and RBC transfusions.