RhD-Alloimmunization in Adult and Pediatric Trauma Patients.

The actual risk of providing RhD-positive units to RhD-negative recipients remains debatable. There is no standard of care in the United States (US) to guide transfusion decisions regarding RhD type for patients with an unknown blood type, except for women of childbearing age and neonates. The risk of alloantibody formation by an RhD-negative patient exposed to RhD-positive blood is reported to be from 3% to 70%. Due to such wide variations, this review was undertaken to determine the prevalence of anti-D alloimmunization in trauma patients who are RhD-negative and were transfused RhD-positive blood products. This study used the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) approach to answer the question, "In trauma patients who were transfused blood, what is the prevalence of alloimmunization to the D-antigen?" The review included all published articles through April 3, 2022 in databases. Articles published after the search period found by the authors were added to the manuscript if they addressed the primary question and there was unanimous consensus. There were 1683 full-text articles that met the search criteria, with 19 studies meeting eligibility criteria. In addition, 57 references were added after the search period had closed. The incidence of anti-D alloimmunization in adult trauma patients receiving whole blood varied from 7.8% to 42.7%. In contrast, incidence varied in patients receiving red blood cells (RBCs), from 0 to 94%, depending on number of categories analyzed. Anti-D alloimmunization with platelet transfusions varied from 0% to 19%. The alloimmunization rate increased with age and was detected only in children older than 5 years. Recent guidelines recommend the administration of Rh immune globulin (RhIG) to all traumatically injured patients who are both RhD-negative and pregnant. However, there is no specific guidance focused on the RhD-negative patient, pregnant or nonpregnant, and who have received RhD-positive red blood cells (RBC) and platelets. While numerous studies have attempted to evaluate the frequency of RhD alloimmunization rate in trauma settings, emerging data suggests that many factors affect this phenomenon. Additionally, the role of RhIG administration in cases of RhD-incompatible transfusions within the trauma setting adds complexity. As our trajectory propels us towards precision medicine and tailored transfusion practices, gaining a big data approach becomes indispensable.

The use of predictive modelling to determine the likelihood of donor return during the COVID-19 pandemic.

Artificial intelligence (AI) uses sophisticated algorithms to "learn" from large volumes of data. This could be used to optimise recruitment of blood donors through predictive modelling of future blood supply, based on previous donation and transfusion demand. We sought to assess utilisation of predictive modelling and AI blood establishments (BE) and conducted predictive modelling to illustrate its use. A BE survey of data modelling and AI was disseminated to the International Society of Blood transfusion members. Additional anonymzed data were obtained from Italy, Singapore and the United States (US) to build predictive models for each region, using January 2018 through August 2019 data to determine likelihood of donation within a prescribed number of months. Donations were from March 2020 to June 2021. Ninety ISBT members responded to the survey. Predictive modelling was used by 33 (36.7%) respondents and 12 (13.3%) reported AI use. Forty-four (48.9%) indicated their institutions do not utilise predictive modelling nor AI to predict transfusion demand or optimise donor recruitment. In the predictive modelling case study involving three sites, the most important variable for predicting donor return was number of previous donations for Italy and the US, and donation frequency for Singapore. Donation rates declined in each region during COVID-19. Throughout the observation period the predictive model was able to consistently identify those individuals who were most likely to return to donate blood. The majority of BE do not use predictive modelling and AI. The effectiveness of predictive model in determining likelihood of donor return was validated; implementation of this method could prove useful for BE operations.

Advances in Human Leukocyte Antigen Testing Technologies and Management Strategies for Platelet Transfusion Refractoriness.

CONTEXT.­: The blood bank is often consulted for transfusion support of patients with suspected platelet transfusion refractoriness (PTR). The workup is complex because testing includes specialized assays that are uncommonly ordered with limited availability. Add to this the variety of possible products-crossmatched platelets, human leukocyte antigen (HLA)-matched platelets, HLA antigen-negative platelets-and the approach to PTR can be overwhelming. Moreover, most literature on the subject is published in transfusion medicine journals aimed at transfusion medicine physicians and blood bank specialists in academic settings. Resources tailored to community hospital blood banks are lacking. OBJECTIVE.­: To provide pathologists who may not have subspecialized training in transfusion medicine and who direct blood banks algorithmic workflows based on clinical scenario and test availability to provide appropriate transfusion support for patients with PTR. DATA SOURCES.­: This review is a comprehensive overview of terminology, HLA testing procedures, interpretations, and practical recommendations for managing PTR in various scenarios based on expert opinion as well as relevant medical literature published from 2007 to 2022. CONCLUSIONS.­: Consultation on PTR is complicated and encompasses many clinical and laboratory aspects. The lack of guidelines derived from high-quality prospective studies poses challenges in the workup and management of PTR. Hindering the process further are limited test availability, unfamiliarity with the technical assays, and the various specialized platelet products. The clinical evaluation algorithm presented herein along with the workflow pathways offer pathologists user-friendly and best-practice guidelines with different options based on the clinical scenario and the tests available.

Is it time for the death knell of single-unit plasma?

BACKGROUND AND OBJECTIVES: A plasma transfusion dose should be weight-based (10-20 mL/kg), which equates to three to four units in an average-sized adult; therefore, the transfusion of single units under most circumstances is sub-therapeutic. MATERIALS AND METHODS: This retrospective observational study examined the prevalence of single-unit plasma transfusion in adults within a 12-hospital system from 1 January 2018, to 31 December 2019. RESULTS: During the study period, 5791 patients received plasma transfusions. The overall prevalence of single-unit plasma was 17.1% for 988 patients. The majority, 3047 (52.6%), occurred at one hospital, 2132 (36.9%) among five hospitals and 612 (10.7%) at the remaining six hospitals. Cardiac and gastrointestinal (GI)/transplant transfused 2707 (46.8%), combined respiratory, neurological, orthopaedic and congenital/dermatology/other comprised 2133 (36.9%) of the six hospitals that transfused less than 200 patients, four (66.7%) transfused single units above the overall prevalence. CONCLUSION: In this hospital system, more than one in six patients received a transfusion of a single plasma unit. Six of the 12 hospitals had 89.5% of the patients who were transfused plasma. Six service lines transfused 83.7% of all patients receiving plasma. Hospitals that infrequently transfused plasma were more likely to under-dose.

When you think you should transfuse don't!

A 48-year-old female presented to the emergency department with severe fatigue. Admission laboratory test results were hemoglobin 6.6 g/dL, platelet count 287,000/µL, and white blood cell count 25,200/µL. Lactate dehydrogenase was elevated at 898 U/L, haptoglobin was markedly decreased (< 31 mg/dL), indirect bilirubin was elevated (5.3 mg/dL), and the absolute reticulocyte count was low at 0.0050/µL. A sample was sent to the immunohematology reference laboratory. The direct antiglobulin test immunoglobulin G was negative; C3 was 1+. All cells were reactive at immediate spin phase, indirect antiglobulin testing (IAT) with polyethylene glycol, with low ionic strength saline, neat, prewarm, and in the solid phase. All cells were nonreactive at IAT-ficin. Additional testing included a cold antibody titer that was 1:4096 and thermal amplitude studies demonstrating reactivity of 2+ at 37°C. These results were consistent with a clinically significant anti-Pr and cold agglutinin disease (CAD). Although rituximab is effective in autoimmune hemolytic anemia, this may take weeks. The patient was treated with pegcetacoplan, a pegylated peptide that targets C3 inhibiting hemolysis. The patient was discharged on day 29 with a hemoglobin of 8 g/dL. This is a report of one of the first patients successfully treated with pegcetacoplan for CAD.

Patient Blood Management and Its Role in Supporting Blood Supply.

Blood donors and voluntary blood donations are essential for ensuring the blood supply that can be maintained by good patient blood management (PBM) practices. This review article explores the role of blood donation in PBM and highlights the importance of donor screening and selection processes in different regions worldwide. The donor health questionnaires and the focused physical examination guidelines have changed in the last decade to increase donor and recipient safety. This article also discusses the status of transfusion practices, including the challenges of ensuring a safe blood supply. Significant among these are the effects of the COVID-19 pandemic on the blood supply chain and the impact of an aging donor population, especially. Promoting autologous donations and other blood conservation strategies are suggested to mitigate these issues. The role of replacement donors and the upper age limit for voluntary blood donation may be decided based on the demography and donor pool. The involvement of C-suite executives is also critical in implementing and running a successful PBM program. The review highlights how these different aspects of blood donation are integral to a successful PBM program and the safety of patients who receive blood transfusions.

Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

The science or not behind deferrals of blood donors with a history of cancer.

BACKGROUND: In the United States (US), each blood center's medical director sets policy for donors with a cancer history. STUDY DESIGN AND METHODS: A subgroup of America's Blood Centers' (ABC) Scientific, Medical, and Technical Committee developed a survey to measure the determination of eligibility, policies for deferral and/or lookback when a donor reports a current diagnosis or history of cancer. A 31-question survey was sent to 47 ABC blood centers in North America via email. Survey results were compiled and literature evaluating the risk of cancer transmission by transfusion was reviewed. RESULTS: Responses were received from 37 centers (79%). Donors with a history of carcinoma or sarcoma who had completed treatment were accepted at 73% of centers with no further deferral. Donors with a history of leukemia or lymphoma were permanently deferred at 76% of centers. Donors with a myelodysplastic or myeloproliferative syndrome were deferred permanently at 86% of centers. Handling of donors with high white cell counts varied. Donors with cancer not in active treatment (i.e., prostate cancer) were subject to various deferrals. Center response to post-donation reports of cancer vary widely. Literature review yielded no evidence of transfusion-transmitted cancer. CONCLUSION: Cancer deferral policies vary widely among blood centers, and are not generally based on evidence, but on some aspect of the precautionary principle. As the donor population ages and so becomes more at risk of cancer, this approach may further reduce the available donor pool.

Patient blood management: Myths and facts about red blood cell transfusions.

Transfusion medicine resembles all of medicine in that expert opinion predominates because hard data on clinical outcomes from randomized controlled trials and high quality observational data are simply unavailable. Indeed, some of the first trials evaluating important outcomes are barely two decades old. Patient blood management (PBM) depends on high quality data for assisting clinicians in making clinical decisions. In this review, we focus on several red blood cell (RBC) transfusion practices that new data suggest need reconsideration. The practices that may need revision include transfusion for iron deficiency anaemia, except in life threatening situations, toleration of anaemia as a largely benign condition and use of haemoglobin/haematocrit as primary indications for RBC transfusion, as opposed to adjuncts to clinical judgement. In addition, the long-standing notion that the minimum transfusion should be two units needs to be abandoned due to the danger to patients and a lack of clinical evidence of benefit. Finally, the difference in indications for leucoreduction versus irradiation needs to be understood by all practitioners. PBM is one of the strategies for managing anaemia and bleeding that holds great promise for patients, and transfusion is only one facet of the bundle of practices.

Cold stored platelets - Increasing understanding and acceptance.

Platelet transfusions decreased the risk of morbidity and mortality secondary to thrombocytopenia. This therapy not only ameliorates platelet loss in bleeding patients,but also those with acquired dysfunction of platelets. The current standard of practice worldwide is to provide room temperature platelets (RTPs); however, there are many disadvantages to the use of RTPs such that alternative approaches have been explored. One potential approach is the integration and use of cold stored platelets (CSP), which are platelets stored at 1-6 °C, in clinical settings. CSP research studies show equivalent hemostasis and platelet dysfunction restoration compared to RTPs. In addition, publications have demonstrated advantages of CSP such as reduced bacterial contamination and wastage. Despite its benefits, the production of CSP by blood centers (BCs) and uptake and use of CSP by hospitals has remained relatively low. This review highlights the rationale for CSP production and strategies for overcoming the implementation challenges faced by BCs based on a literature review.Experiences of Consortium for Blood Availability members to integrate CSP in their BCs and clinical practices by providing variance applications are reviewed in this paper. Also, demonstrated in this manuscript are the current indications and opportunities for CSP utilization by healthcare providers.

Patient blood management using dedicated personnel in the operating room-you get what you pay for.

A patient blood management (PBM) strategy can be applied to the process of intraoperative cell salvage for re-infusion during surgery. Stoneham et al. describe an effective PBM strategy applied to abdominal aortic aneurysm repair and emphasise the importance of a qualified and experienced intraoperative cell salvage practitioner to improve the safety and effectiveness of the approach. Commentary on: Stoneham et al. Intraoperative cell salvage using swab wash and serial thromboelastography in elective abdominal aortic aneurysm surgery involving massive blood loss. Br J Haematol 2023;200:652-659.

Comparison of RhD Typing Results by Serology and Molecular Methods.

OBJECTIVE: Molecular testing determines D antigen status when abnormal serologic results are observed. Molecular testing is routinely batched, resulting in longer turnaround time for abnormal D status resolution. During the interim, obstetric patients with questionable/uninterpretable and weak D typing results by serology, per the immunohematology reference laboratory (IRL) policy, will receive RhD negative blood. This study aimed to determine whether serology results achieved a concordance. METHODS: Six hospitals provided samples to the IRL (first IRL) for RhD status by DNA. De-identified samples were sent for serology RhD (second IRL). A concordance of ≥80% was acceptable. RESULTS: Forty-nine samples were evaluated. Results were concordant (65.3% [32/49]) and discordant (34.7% [17/49]). This is significantly lower than clinically acceptable 80% (z = 2.57, P < .05). The turnaround-time was 3.0 hours for serology and 4.4 days for molecular evaluation. CONCLUSION: Due to a low concordance, serology could not be used in place of molecular testing.

Critical conversations on patient blood management with clinical colleagues.

Although a subspecialty-trained transfusion medicine (TM) physician brings value to the clinical bedside, hospital transfusion service oversight often falls under the responsibility of pathologists primarily focused on surgical pathology. Yet, pathologists who lack TM fellowship training may not be quite as confident in their role as the TM physician in-charge, especially when the need to communicate with another clinician arises. Given that blood is a resource subject to frequent shortages, there is a need for constant monitoring of blood utilization such that those responsible for transfusion service oversight need to handle challenging clinical interactions when transfusion guidelines are breeched. Generally, the average pathologist is more knowledgeable regarding blood component therapy than other clinician. Yet, disagreements concerning patient transfusion management can arise, in spite of established evidence-based hospital transfusion guidelines. Since authoritative fact stating is not likely to be effective in changing the entrenched practices, pathologists must engage in strategies that will develop meaningful working relationships with their clinical colleagues. Such strategies include being a visible part of direct patient care, such as attendance at patient rounds or provision of mini-consultations by phone regarding transfusion management. Inviting clinicians to attend the hospital transfusion committee meetings and scheduling educational grand rounds are also useful strategies. Clinicians may be more receptive to blood conservation during times of shortages if open communication is established, particularly if hospital leadership is involved in urgent crisis messaging to the clinicians and other hospital staff involved in patient care.

Transfusion therapy of neonatal and paediatric patients: They are not just little adults.

Patient blood management (PBM) strategies are needed in the neonate and paediatric population, given that haemoglobin thresholds used are often higher than recommended by evidence, with exposure of children to potential complications without meaningful benefit. A literature review was performed on the following topics: evidence-based transfusions of blood components and pharmaceutical agents. Other topics reviewed included perioperative coagulation assessment and perioperative PBM. The Transfusion and Anaemia Expertise Initiative (TAXI) consortium published a consensus statement addressing haemoglobin (Hb) transfusion threshold in multiple subsets of patients. A multicentre trial (PlaNeT-2) reported a higher risk of bleeding and death or serious new bleeding among infants who received platelet transfusion at a higher (50 000/µl) compared to a lower (25 000/µl) threshold. Recent data support the use of a restrictive transfusion threshold of 25 000/µl for prophylactic platelet transfusions in preterm neonates. The TAXI-CAB consortium mentioned that in critically ill paediatric patients undergoing invasive procedures outside of the operating room, platelet transfusion might be considered when the platelet count is less than or equal to 20 000/µl and there is no benefit of platelet transfusion when the platelet count is more than 50 000/µl. There are limited controlled studies in paediatric and neonatal population regarding plasma transfusion. Blood conservation strategies to minimise allogenic blood exposure are essential to positive patient outcomes neonatal and paediatric transfusion practices have changed significantly in recent years since randomised controlled trials were published to guide practice. Additional studies are needed in order to provide practice change recommendations.

Early and out-of-hospital use of COVID-19 convalescent plasma: An international assessment of utilization and feasibility.

BACKGROUND AND OBJECTIVES: The use of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) in the treatment of patients with severe acute respiratory syndrome-2 infection has been controversial. Early administration of CCP before hospital admission offers a potential advantage. This manuscript summarizes current trials of early use of CCP and explores the feasibility of this approach in different countries. MATERIALS AND METHODS: A questionnaire was distributed to the International Society of Blood Transfusion (ISBT) CCP working group. We recorded respondents' input on existing trials on early/outpatient CCP and out-of-hospital (OOH)/home transfusion (HT) practices in their countries and feedback on challenges in initiating home CCP infusion programmes. In addition, details of existing trials registered on clinicaltrials.gov were summarized. RESULTS: A total of 31 country representatives participated. Early/OOH CCP transfusion studies were reported in the United States, the Netherlands, Spain and Brazil. There were a total of six published and five ongoing trials on the prophylactic and therapeutic early use of CCP. HT was practised in Australia, the UK, Belgium, France, Japan, Nigeria, the Netherlands, Spain, Italy, Norway, the United States and some provinces in Canada. Thirty-four representatives indicated a lack of OOH CCP or HT in their institutions and countries. Barriers to implementation of OOH/HT included existing legislation, lack of policies pertaining to outpatient transfusion, and associated logistical challenges, including lack of staffing and resources. CONCLUSION: Early administration of CCP remains a potential option in COVID-19 management in countries with existing OOH/HT programmes. Legislation and regulatory bodies should consider OOH/HT practice for transfusion in future pandemics.

How do we obtain and maintain patient blood management certification?

BACKGROUND: The creation of a patient blood management (PBM) certification program by The Joint Commission (TJC) and Association for the Advancement of Blood and Biotherapies (AABB) provides validation of an existing PBM program. MATERIALS AND METHODS: A team of subject matter experts in PBM formed a working group to develop a structured approach to guide PBM programs through the PBM certification. Program challenges and metrics were reviewed. RESULTS: Initial steps to establishing PBM certification include a multidisciplinary working group and hospital administration buy-in. Development of policies and procedures individualized to the facility will standardize practice. An institutional transfusion committee can provide PBM oversight including enforcing compliance. Using resources such as TJC and AABB standards and tools including electronic medical records (EMR) can track and trend hospital PBM performance and identify improvement opportunities. A gap analysis tool helps implementation. Challenges might include maintaining a PBM program during a merger, slow responsiveness of information systems (IS) to requests, PBM education for both the Transfusion Safety Officer (TSO) and hospital staff with constant turnover. Available metrics from one hospital system showed good compliance with transfusion thresholds (average all products: 97.9%, 2019, 2020). In 2020, through educational efforts the cost savings were $124,856.70 compared to 2019. Regarding single unit transfusion of RBCs, this was 62.25% (2019), 63.75% (2020), 72.00% (2021), and surpassed the target goal of 60%. CONCLUSIONS: Obtaining PBM certification highlights the success of an institution's PBM program. Facilities that have achieved PBM certification have seen significant reductions in transfusions and considerable cost savings.

Acquired platelet storage container leaks and contamination with environmental bacteria: A preventable cause of bacterial sepsis.

BACKGROUND: Apheresis platelets (AP) may be contaminated by environmental bacteria via container defects acquired during processing, transport, storage, or transfusion, as highlighted by a recent series of septic reactions related to Acinetobacter spp. and other bacterial strains. STUDY DESIGN AND METHODS: The frequency and nature of acquired container defect reports to one manufacturer were evaluated from January 2019 to July 2020. The published incidence of contamination and sepsis due to environmental bacteria with culture screened AP in the United States was reviewed for the period of 2010-2019. RESULTS: Review of a manufacturers' records showed 23 US reports of leaks involving 24 containers attributed to postmanufacturing damage, at a rate of 44 per million distributed storage containers. Analysis of returned containers showed evidence of scratches, impressions, and/or piercings. Literature review of US hemovigilance data revealed that environmental bacteria comprised 7% of confirmed positive primary bacterial culture screens, were responsible for 14%-16% of reported septic, and 8 of 28 (29%) fatal reactions with bacterial-culture screened AP. Sepsis cases have been reported with culture screened, point-of-issue (POI) tested, or pathogen-reduced AP. DISCUSSION: Environmental contamination of AP is rare but can cause sepsis. Container damage provides a pathway for contamination after culture screening, POI bacteria testing, or pathogen reduction. Blood collectors and transfusion services should have procedures to ensure proper inspection, handling, storage, and transport of AP to avoid damage and should enhance efforts to detect defects prior to release and to eliminate bacteria from all contacting surfaces to minimize the risk of contamination.