Serologic reactivity of unidentified specificity in antenatal testing and hemolytic disease of the fetus and newborn: The BEST collaborative study.

BACKGROUND: The clinical significance of serologic reactivity of unidentified specificity (SRUS) in pregnancy is not clear based on available literature. The aim of this study is to determine if SRUS is associated with hemolytic disease of the fetus and newborn (HDFN). STUDY DESIGN AND METHODS: Retrospective data were collected from eight institutions over an 11-year study period (2010-2020), when available (5/8 sites). The outcome of the pregnancies with SRUS-no, mild, moderate, or severe HDFN-was determined. RESULTS: SRUS was demonstrated in 589 pregnancies. After excluding those with incomplete data, a total of 284 pregnancies were included in the primary HDFN outcome analysis. SRUS was detected in 124 (44%) pregnancies in isolation, and none were affected by HDFN. Of 41 pregnancies with SRUS and ABO incompatibility, 37 (90%) were unaffected, and 4 (10%) were associated with mild HDFN. Of 98 pregnancies with SRUS and concurrent identifiable antibody reactivity(s), 80 (81%) were unaffected, and 19 (19%) were associated with mild to severe HDFN. There was 1 case of mild HDFN and 1 case of severe HDFN in the 21 pregnancies with SRUS, ABO incompatibility, and concurrent identifiable antibody reactivity(s), and 19 (90%) were unaffected by HDFN. Among all patients with repeat testing, newly identified alloantibodies or other antibodies were identified in 63 of 212 (30%) patients. Although most were not clinically significant, on occasion SRUS preceded clinically significant antibody(s) associated with HDFN (3%, 5/188). CONCLUSION: The antenatal serologic finding of SRUS in isolation is not associated with HDFN but may precede clinically significant antibodies.

Transfusion outcomes between regular and low yield pathogen reduced platelets across different patient populations in a single institution.

BACKGROUND: Pathogen reduction technology (PRT) effectively mitigates bacterial contamination in platelets but is more likely to produce low yield units. Although low dose transfusion using conventional platelets has not been associated with increased bleeding, these findings have not been reproduced with PRT-treated platelets. STUDY DESIGN AND METHODS: Platelet transfusions in a tertiary adult hospital were retrospectively reviewed. Comparisons were made between PRT-treated regular (PRT-PR) and low (PRT-PL) yield platelets. Outcomes examined included the number of platelets and RBCs transfused, transfusion-free interval, and corrected count increment (CCI). Subgroup analyses were also performed on hematology-oncology inpatients and outpatients, as well as non-hematology-oncology patients. RESULTS: Platelet utilization per patient remained mostly unchanged (mean 2.9-4.3 units per patient per month) even when the frequency of PRT-PL transfusion increased. Among 1402 patients examined, the number of platelets and RBCs transfused was not significantly different between patients first transfused with PRT-PR versus PRT-PL (mean number of platelet units = 2.8 vs. 3.1, p = 0.38; mean number of RBC units = 4.8 vs. 4.3, p = 0.93). Among 10,257 platelet transfusions examined, the transfusion-free interval (hazard ratio = 1.05, 95% confidence interval 1.00-1.10) and CCI (10.2 vs. 11.0, p = 0.70) were comparable between PRT-PR and PRT-PL units. Similar findings were observed in all subgroups, except for shortened transfusion-free intervals among hematology-oncology inpatients. CONCLUSION: PRT-PR and PRT-PL units may be used in an equivalent manner to maintain an adequate platelet inventory, since there was only a minor difference in time between transfusions.

Validated transport conditions maintain the quality of washed red blood cells.

BACKGROUND: Washing red blood cell (RBC) units prior to transfusion is indicated for certain patients. In the United States, units stored at 1°C-6°C or transported at 1°C-10°C are available for issue up to 24 h, if not used immediately. The washing procedure commonly utilizes room temperature saline resulting in units starting out above the allowed temperature range. This leads to wastage if units are issued and returned too quickly before having a chance to equilibrate in a transport cooler. STUDY DESIGN AND METHODS: Here we performed an experimental study of washed RBC quality comparing "ideal" storage conditions in a blood bank refrigerator to a "real-world" simulation of unit transport, including holding in a transport cooler. Twelve RBC units were washed and allocated evenly into either condition. RESULTS: Measurements at 0, 1, 3, 6, 12, and 24 h post-washing revealed that placement in a transport cooler was associated with higher unit temperature prior to 12 h (p = .013) with a maximum difference of 9.3°C. Despite this difference, several measures of unit quality including extracellular potassium, pH, lactate, and free hemoglobin were indistinguishable between conditions (p = .382, .224, .286, .691, respectively). We selected half of the tested units from our irradiated inventory and confirmed increased potassium leak (p < .001) and accumulation of free hemoglobin (p = .012) in irradiated units. DISCUSSION: Washed units stored under approved transport conditions are acceptable to return to inventory up to 24 h after washing and we provide a prediction interval-based temperature threshold for rejecting these units, permitting reduced waste.

How do I implement pathogen-reduced platelets?

BACKGROUND: Several risk mitigation steps have improved the safety of platelets in regard to bacterial contamination, but this continues to be a concern today. A Food and Drug Administration (FDA) Guidance issued in December 2018 aims to further limit this risk. The guidance offers multiple pathways for compliance, and hospital blood banks will have to collaborate with blood donor centers to assess various factors before deciding which method is most appropriate for them. METHODS AND MATERIALS: Our institution considered several factors before moving forward with pathogen reduction technology. This included an assessment of platelet shelf-life, bacterial testing requirements, the efficacy of low-yield platelets, and managing a mixed platelet inventory. The decision to transition to pathogen-reduced platelets was associated with complex collection and processing limitations that resulted in either an increase in platelets that were over-concentrated or products with a low platelet yield. RESULTS: Through trials of various collection settings with unique target volumes and target platelet yields, our blood donor center was able to optimize the production. At the hospital end, this transition required a thorough review of low-yield platelet products and their clinical efficacy. Additionally, this implementation necessitated collaboration with clinical colleagues, comprehensive education, and training. CONCLUSIONS: Pathogen-reduced platelets would be the most efficient way for our institution to be compliant. This summary may serve as a roadmap for other institutions that are considering which FDA prescribed method to use and provide support for those that have decided on pathogen reduction technology but need to optimize their collections to best utilize low-yield products.

Optimizing O-negative RBC utilization using a data-driven approach.

BACKGROUND: O-negative red blood cells (ON-RBC) are a precious resource and the international blood banking community has become increasingly concerned with its inappropriate utilization. AABB recently made several recommendations to address the issue. Solutions must be multifaceted and involve donor centers, blood banks, and clinical departments. From the perspective of a hospital blood bank, it is difficult to rely solely on increased donor recruitment and ubiquitous blood typing of the entire in-patient population. We therefore focused on interventions within the blood bank to optimize inventory and policies to ensure appropriate ON-RBC utilization. STUDY DESIGN AND METHODS: Transfusion data over one year was examined for the rate of out-of-group/inappropriate ON-RBC. Furthermore, we assessed whether that rate was related to product life on the day of transfusion. We also examined our stock inventory levels and how excess inventory can contribute to inappropriate ON-RBC usage. RESULTS: The ON-RBC inventory level was decreased in order to reduce the rate of inappropriate transfusions while maintaining a safe level for optimal patient care. Compared to baseline, our intervention caused ON-RBCs to be transfused earlier in their shelf-life (9.27 vs. 11.15 days from expiration [DFE], p = 0.0012). This reduced the overall rate of inappropriate ON-RBC transfusions (67% vs. 54%, p = 0.0035), approximating 185 units of ON-RBC saved over the course of 6 months. CONCLUSIONS: A data-driven approach to optimize stock inventory levels is widely applicable; it can be adopted by numerous institutions to improve utilization and establish a benchmark for the broader blood banking community.

Comparison of the solid-phase red cell adherence assay and tube method for detection and identification of red blood cell antibodies.

OBJECTIVES: Identifying antibodies to red blood cell antigens is one of transfusion medicine's critical responsibilities. The International Society of Blood Transfusion recognizes 354 red blood cell antigens. Accurate identification of clinically significant alloantibodies is imperative for preventing hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. We compared the performance of the tube (polyethylene glycol-indirect antiglobulin test [PEG-IAT]) and solid-phase red cell adherence assay techniques. METHODS: We performed a retrospective study on all antibody screens performed between 2007 and 2021 at Stanford Transfusion Services. Initially, 631,535 antibody screens were performed using a solid-phase technique. Subsequent antibody identifications were performed using a combination of tube testing and solid-phase techniques. RESULTS: Antibody screening resulted in 28,316 (4.5%) positive samples. Antibody identification performed on both platforms identified 50 discordant samples. The anti-E antibody had the lowest sensitivity (98.99%) in the automated solid-phase technique, while anti-Jkb had the lowest sensitivity (98.78%) with the PEG-IAT method. CONCLUSIONS: To our knowledge, this is the first robust, 15-year study comparing methodologic sensitivity to detect clinically significant alloantibodies. The incidence of discordant results between PEG-IAT and the solid-phase technique was low. Among discordant samples, anti-Jka was commonly detected using the solid-phase method but not with the PEG-IAT. In contrast, anti-E was commonly detected by PEG-IAT but not by the solid-phase method.

Implementation and early outcomes with Pathogen Reduced Cryoprecipitated Fibrinogen Complex.

OBJECTIVES: Cryoprecipitated antihemophilic factor (cryo) has been used for fibrinogen replacement in actively bleeding patients, dysfibrinogenemia, and hypofibrinogenemia. Cryo has a shelf life of 4 to 6 hours after thawing and a long turnaround time in issuing the product, posing a major limitation of its use. Recently, the US Food and Drug Administration approved Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex [IFC]) for the treatment of bleeding associated with fibrinogen deficiency, which can be stored at room temperature and has a shelf life of 5 days after thawing. METHODS: We identified locations and specific end users with high cryoprecipitate utilization and waste. We partnered with our blood supplier to use IFC in these locations. We analyzed waste and turnaround time before and after implementation. RESULTS: Operative locations had a waste rate that exceeded nonoperative locations (16.7% vs 3%) and were targeted for IFC implementation. IFC was added to our inventory to replace all cryo orders from adult operating rooms, and waste decreased to 2.2% in these locations. Overall waste of cryoprecipitated products across all locations was reduced from 8.8% to 2.4%. The turnaround time for cryoprecipitated products was reduced by 58% from 30.4 minutes to 14.6 minutes. CONCLUSIONS: There has been a substantial decrease in waste with improved turnaround time after IFC implementation. This has improved blood bank logistics, improved efficiency of patient care, and reduced costly waste.

Multinational Analysis of Children Transfused With Pathogen Inactivated Platelets.

BACKGROUND: Pathogen inactivated (PI) platelets are a technological advancement in blood safety; however, the pediatric experience is not well characterized. We studied pediatric patients who received transfusions of PI platelets across several centers and countries to determine if transfusion reaction rates differed when compared with conventional platelets. METHODS: This is a retrospective multisite study conducted during 2 time periods. The study period started at the time each site began using PI platelets on a widespread basis, and the control period was a similar timespan before PI introduction. Suspected acute transfusion reactions were compared. RESULTS: The study included 3839 pediatric patients who were 0 to 18 years of age who received >7930 platelet transfusions, in total, across 4 centers in 3 countries between 2013 and 2019. The age distribution of patients in the study and control period was not significantly different (P = .190). There was not a difference in the percentage of patients who had any type of transfusion reaction between the time periods (1.0% and 1.1%, P = .803). There were fewer patients with mild allergic reactions in the study period compared with the control period (0.2% and 0.7% of patients with reactions, respectively, P = .018). CONCLUSIONS: Pediatric patients have the same rate of acutely suspected transfusion reactions when receiving PI or conventional platelet transfusions. Subgroup analysis found fewer mild allergic reactions in the study period, which was contemporaneous to the addition of using platelet additive solution more broadly. Future studies of PI platelets should include children to better assess transfusion efficacy and hemostatic outcomes.

Establishing a Satellite Transfusion Service Within an Academic Medical Center.

OBJECTIVES: Increasingly complex medical care requires specialized transfusion support close at hand. Hospital growth can necessitate expansion of blood bank services to new locations to ensure rapid delivery of blood products. We describe the opening of a new satellite transfusion service designed to serve the needs of a pediatric hospital. METHODS: Institutional transition teams and stakeholders collaborated to discuss options for providing blood at a new pediatric hospital. A staffed satellite transfusion service met the diverse needs of multiple services and was considered a compromise between a full new transfusion service and automated solutions. RESULTS: Initial challenges in establishing the laboratory included regulatory uncertainty and interactions between two hospitals' information technology services. Laboratory scientist staffing and actual use required adapting the satellite service to an emergency release-only model. CONCLUSIONS: A flexibly staffed satellite transfusion service met the most urgent needs of a pediatric hospital expansion. Review of implementation revealed potential process improvements for future expansions, including comprehensive routine and massive transfusion simulations. The challenges experienced in supplying staff and specialized blood products track with national trends. Other institutions may consider establishing a satellite transfusion service in the context of both increasingly sophisticated automated solutions and complex blood needs.

Blood Donation During Pregnancy Due to Anti-Ku Hemolytic Disease of the Fetus and Newborn.

BACKGROUND: Management of pregnancy in patients with Kell-null phenotype can be challenging. The immune systems of these patients form an antibody that is universally reactive against the Kell Blood Group System and can cause hemolytic disease of the fetus and newborn. METHODS: A 29-year-old woman, pregnant for the first time, developed anti-D and anti-Ku. The mother had to have labor induced when her fetus showed signs of severe anemia, but no compatible blood was available for transfusion. The induction was delayed so that a unit of blood could be collected from the mother. RESULTS: Due to delayed cord clamping at delivery, the newborn did not have anemia and did not require a transfusion. The remaining blood was frozen for future needs. CONCLUSION: Blood donation by a pregnant woman for potential transfusion to a newborn with anemia is safe for the mother and fetus, and is possibly the only option in hemolytic disease of the newborn due to a rare antibody.

Severe Underestimation of Serum Na following IVIG Treatment.

Current chemistry analyzers measure ion concentration using ion- selective electrodes; however, may differ in the specific technology at the bedside versus the central laboratory. Instruments utilized for point-of-care testing (POCT) at the bedside use direct ion-selective electrodes, whereas central-laboratory analyzers use indirect ion-selective electrodes. Under most circumstances, these instruments will deliver the same result; however, various substances can cause interferences in one or the other. An 18-year-old Hispanic woman with a history of immune thrombocytopenic purpura (ITP) presented at Children's National Medical Center (CNMC) with a severe headache and required intravenous immunoglobulin (IVIG) therapy. Because a discrepancy developed between her point-of-care and central-laboratory sodium values, another instrument was used to retest the central-laboratory plasma specimens. The results were more in agreement with those from the point-of-care instrument and revealed a unique interference in sodium measurement related to IVIG use.

Rh Immunoprophylaxis for Women With a Serologic Weak D Phenotype.

It is standard practice for pregnant RhD-negative women who have not already formed anti-D to receive antepartum Rh immunoprophylaxis and, if they deliver an RhD-positive neonate, to receive postpartum Rh immunoprophylaxis. An estimated 0.6% to 1.0% of white women have red blood cells that express a serologic weak D phenotype. Of these women, approximately 80% will have a weak D type 1, 2, or 3 that could be managed safely as RhD-positive. Surveys of laboratory practice reveal a lack of standards for interpreting the RhD type for women with a serologic weak D and for determining their need for Rh immunoprophylaxis. RhD genotyping is recommended to determine the molecular basis of serologic weak D phenotypes in pregnant women as a basis for determining their candidacy for Rh immunoprophylaxis.