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.

The importance of ABO in platelet refractoriness, an often overlooked option.

ABO-non-identical (ni) platelets provide less of an increase in platelet count and may increase the length of patient transfusions. The paper by Han and Badami showed that ABO-ni platelets may be a risk factor for immune platelet transfusion refractoriness. Commentary on: Han et al. ABO non-identical platelet transfusions, immune platelet refractoriness and platelet support. Br J Haematol 2024;204:2097-2102.

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.

How do I manage a blood product shortage?

BACKGROUND: The demand for blood products sometimes exceeds the available inventory. Blood product inventories are dependent upon the availability of donors, supplies and reagents, and collection staff. During prolonged extreme shortages, blood centers and transfusion services must alter practices to meet the needs of patients. STUDY DESIGN AND METHODS: The Association for the Advancement of Blood and Biotherapies Donor and Blood Component Management Subsection compiled some strategies from its blood center and hospital transfusion service members that could be implemented during blood product shortages. RESULTS: Some strategies that blood centers could use to increase their available inventories include increasing donor recruitment efforts, using alternate types of collection kits, manufacturing low-yield apheresis-derived platelets and/or whole blood-derived platelets, using cold-stored platelets, transferring inventory internally among centers of the same enterprise, using frozen inventory, decreasing standing order quantities, prioritizing allocation to certain patient populations, filling partial orders, and educating customers and blood center staff. Transfusion service strategies that could be implemented to maximize the use of the limited available inventory include increasing patient blood management efforts, using split units, finding alternate blood suppliers, trading blood products with other hospital transfusion services, developing a patient priority list, assembling a hospital committee to decide on triaging priorities, using expired products in extreme situations, and accepting nonconforming products after performing safety checks. DISCUSSION: Blood centers and transfusion services must choose the appropriate strategies to implement based on their needs.

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.

Managing blood supplies during natural disasters, humanitarian emergencies, and pandemics: lessons learned from COVID-19.

INTRODUCTION: The COVID-19 pandemic has resulted in a historic public health crisis with widespread social and economic ramifications. The pandemic has also affected the blood supply, resulting in unprecedented and sustained blood shortages. AREAS COVERED: This review describes the challenges of maintaining a safe and sufficient blood supply in the wake of natural disasters, humanitarian emergencies, and pandemics. The challenges, which are accentuated in low- and high-income countries, span the impact on human capacity (affecting blood donors and blood collections personnel alike), disruption to supply chains, and economic sustainability. COVID-19 imparted lessons on how to offset these challenges, which may be applied to future pandemics and public health crises. EXPERT OPINION: Pandemic emergency preparedness plans should be implemented or revised by blood centers and hospitals to lessen the impact to the blood supply. Comprehensive planning should address the timely assessment of risk to the blood supply, rapid donor recruitment, and communication of need, measures to preserve safety for donors and operational staff, careful blood management, and resource sharing.

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.

Beyond COVID-19 and lessons learned in the United States.

The COVID-19 pandemic severely tested the resilience of the US blood supply with wild fluctuations in blood donation and utilisation rates as community donation opportunities ebbed and hospitals post-poned elective surgery. Key stakeholders in transfusion services, blood centres, supply chains and manufacturers reviewed their experiences during the SARS-CoV-2 pandemic as well as available literature to describe successes, opportunities for improvement and lessons learned. The blood community found itself in uncharted territory responding to restriction of its access to donors (approximately 20% decrease) and some supplies; environmental adjustments to address staff and donor concerns about coronavirus transmission; and the development of a new product (COVID-19 convalescent plasma [CCP]). In assuring that the needs of the patients were paramount, the donation process was safe, that clinicians had access to CCP, and vendor relationships aligned, the blood banking community relearned its primary focus: improving patient outcomes.

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.