A randomized control trial to compare mortality in recipients of leucoreduced and non-leucoreduced whole blood transfusion in patients with cancer in Uganda.

BACKGROUND: Mortality benefit of transfusion with leucoreduced whole blood has not been demonstrated in the sub-Saharan Africa (SSA). We compared mortality in patients with cancer transfused with leucoreduced and non-leucoreduced whole blood in a SSA setting. METHODS: An open-label randomized controlled trial was conducted at the Uganda Cancer Institute where participants were randomized in a 1:1 ratio into the leucoreduced and non-leucoreduced whole blood transfusion arms. Leucocyte filtration of whole blood was performed within 72 h of blood collection. Patients aged ≥ 15 years who were prescribed blood transfusion by the primary physicians were eligible for study enrolment. Mortality difference was analyzed using intention-to-treat survival analysis and cox proportional hazard model was used to analyze factors associated with mortality. RESULTS: There were 137 participants randomized to the leucoreduced and 140 to the non-leucoreduced arms. Baseline characteristics were similar between the two arms. The median number of blood transfusions received was 1 (IQR, 1-3) unit and 2 (IQR, 1-3) units in the leucoreduced and non-leucoreduced arms respectively, p = 0.07. The 30-day mortality rate in the leucoreduced arm was 4.6% (95% CI, 2.1-10) and was 6.2% (95% CI, 3.2-12.1) in the non-leucoreduced arm (p = 0.57), representing an absolute effect size of only 1.6%. Increasing age (HR = 0.92, 95% CI, 0.86-0.98, p = 0.02) and Eastern Co-operative Oncology Group (ECOG) performance score of 1 (HR = 0.03, 95% CI, 0.00-0.31, p < 0.01) were associated with reduced 30-day mortality. CONCLUSIONS: The study failed to demonstrate mortality difference between cancer patients transfused with leucoreduced and non-leucoreduced whole blood. Although this study does not support nor refute universal leucoreduction to reduce mortality in patients with cancer in SSA, it demonstrates the feasibility of doing transfusion RCTs in Uganda, where a multi-center trial with an appropriate sample size is needed. TRIAL REGISTRATION: Pan African Clinical Trial Registry, https://pactr.samrc.ac.za/ (PACTR202302787440132). Registered on 06/02/2023.

Preoperative Blood Transfusion Requirements for Hemorrhoidal Severe Anemia: A Retrospective Study of 128 Patients.

BACKGROUND Severe anemia caused by hemorrhoidal hematochezia is typically treated preoperatively with reference to severe anemia treatment strategies from other etiologies. This retrospective cohort study included 128 patients with hemorrhoidal severe anemia admitted to 3 hospitals from September 1, 2018, to August 1, 2023, and aimed to evaluate preoperative blood transfusion requirements. MATERIAL AND METHODS Of 5120 patients with hemorrhoids, 128 (2.25%; male/female: 72/56) experienced hemorrhoidal severe anemia, transfusion, and Milligan-Morgan surgery. Patients were categorized into 2 groups based on their preoperative hemoglobin (PHB) levels after transfusion: PHB ≥70 g/L as the liberal-transfusion group (LG), and PHB <70 as the restrictive-threshold group (RG). The general condition, bleeding duration, hemoglobin level on admission, transfusion volume, length of stay, immune transfusion reaction, surgical duration, and hospitalization cost were compared between the 2 groups. RESULTS Patients with severe anemia (age: 41.07±14.76) tended to be younger than those with common hemorrhoids (age: 49.431±15.59 years). The LG had a significantly higher transfusion volume (4.77±2.22 units), frequency of immune transfusion reactions (1.22±0.58), and hospitalization costs (16.69±3.31 thousand yuan) than the RG, which had a transfusion volume of 3.77±2.09 units, frequency of immune transfusion reactions of 0.44±0.51, and hospitalization costs of 15.00±3.06 thousand yuan. Surgical duration in the LG (25.69±14.71 min) was significantly lower than that of the RG (35.24±18.72 min). CONCLUSIONS Patients with hemorrhoids with severe anemia might require a lower preoperative transfusion threshold than the currently recognized threshold, with an undifferentiated treatment effect and additional benefits.

Amniotic fluid embolism rescued using venoarterial extracorporeal membrane oxygenation without initial anticoagulation: A case report and literature review.

RATIONALE: Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric disseminated intravascular coagulation (DIC) with bleeding tendency; therefore, the introduction of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is challenging. We report the case of a patient with AFE requiring massive blood transfusion, rescued using VA-ECMO without initial anticoagulation. PATIENTS CONCERNS: A 39-year-old pregnant patient was admitted with a complaint of abdominal pain. An emergency cesarean section was performed because a sudden decrease in fetal heart rate was detected in addition to DIC with hyperfibrinolysis. Intra- and post-operatively, the patient had a bleeding tendency and required massive blood transfusions. After surgery, the patient developed lethal respiratory and circulatory failure, and VA-ECMO was introduced. DIAGNOSIS: Based on the course of the illness and imaging findings, the patient was diagnosed with AFE. INTERVENTIONS: By controlling the bleeding tendency with a massive transfusion and tranexamic acid administration, using an antithrombotic ECMO circuit, and delaying the initiation of anticoagulation and anti-DIC medication until the bleeding tendency settled, the patient was managed safely on ECMO without complications. OUTCOMES: By day 5, both respiration and circulation were stable, and the patient was weaned off VA-ECMO. Mechanical ventilation was discontinued on day 6. Finally, she was discharged home without sequelae. LESSONS: VA-ECMO may be effective to save the lives of patients who have AFE with lethal circulatory and respiratory failure. For safe management without bleeding complications, it is important to start VA-ECMO without initial anticoagulants and to administer anticoagulants and anti-DIC drugs after the bleeding tendency has resolved.

The Year in Review: Anesthesia for Congenital Heart Disease 2023.

This review highlights published literature in 2023 that is related to the anesthetic management of patients with congenital heart disease (CHD). Though not inclusive of all topics, 31 articles are discussed and four primary themes emerged: transfusion and hemostasis, outcomes and risk assessment, monitoring, and pharmacology.

Impact of perioperative blood transfusion on prognosis after nephrectomy in patients with renal cell carcinoma: A meta-analysis and systematic review.

BACKGROUND: Perioperative blood transfusion (PBT) has been associated with worse prognosis in several malignancies. For renal cell carcinoma (RCC), the effect of PBT is still debated. OBJECTIVE: To evaluate the impact of PBT on prognosis after nephrectomy in patients with RCC. METHODS: This study is A systematic review and meta-analysis of published article data (PRISMA protocol) for literature related to PBT and RCC through extensive search of EMBASE, Medline via PubMed, Web of Science and Cochrane Library, language limited to English, with no time constraint until May 20, 2022. We pooled the results of multivariable cox regression analyses from each study, with subgroup analyses by dose and timing of transfusion. All analyses were done using Stata14. RESULTS: A total of 12 studies involving 27,683 participants were included. Our meta-analysis pooled the results of multivariable cox regression analysis in each study, showing that PBT is associated with higher overall Mortality (OM; hazard ratio [HR] = 1.34, 1.23-1.44), cancer-specific mortality (CSM; HR = 1.35, 1.20-1.51), and disease recurrence (HR = 1.54, 1.18-1.89). when only patients with nonmetastatic RCC were included, PBT was still associated with higher OM (HR = 1.29, 1.11-1.47) and disease recurrence (HR = 1.58, 1.18-1.98), but the association with CSM (HR = 1.26, 0.99-1.52) was not statistically significant. In subgroup analysis by transfusion dose, small (1-2) units of PBT were not associated with CSM (HR = 1.84, 0.95-2.73), but large (≥3) units were associated with higher CSM (HR = 2.98, 1.74-4.22) and disease recurrence (HR = 1.99, 1.31-2.67). Each additional unit of PBT resulted in a higher CSM (HR = 1.07, 1.04-1.10). In subgroup analysis by transfusion timing, intraoperative transfusion was associated with higher CSM and disease recurrence, but postoperative transfusion was not. CONCLUSIONS: PBT is associated with higher OM, CSM and disease recurrence. This adverse effect seems to be particularly significant in high-dose intraoperative transfusion. It is necessary to limit the overuse of PBT, especially high-dose intraoperative transfusion, in order to improve the prognosis of patients undergoing nephrectomy for RCC.

How do we leverage data through replication and warehousing to meet blood collection and transfusion service needs.

BACKGROUND: With the widespread adoption of Blood Establishment Computer Systems and other Blood Collection and Transfusion Service (BCTS) clinical information systems (CIS), electronic blood donor, product, and patient data are now routinely required for clinical, regulatory, operational, and quality needs. That data are often not readily accessible for such secondary use within CIS databases, particularly for applications with significant data availability requirements such as machine learning and artificial intelligence. Data replication provides one avenue by which CIS data can be made more readily available. STUDY DESIGN AND METHODS: Members of the AABB's Information Systems Committee along with institutional information technology colleagues provided a multi-institutional viewpoint on data replication through the lens of BCTS specific use cases. Case studies of informatics offerings leveraging such technologies were also elicited. RESULTS: Six distinct use cases describe the potential role of data replication including the creation of data warehouses for frontline laboratory staff. Specific BCTS examples for each use case are presented to highlight the value of data replication, including visualization of critical inventory (O red blood cells, HLA-compatible platelets) and utilization analytics for patient blood management. Two case studies describe the approach to implement such technologies to (1) optimize staffing via laboratory workload reporting and (2) improve access to blood via antigen-negative blood product location services. DISCUSSION: Data replication and warehousing can empower BCTS analytic offerings not otherwise natively available through one's CIS to improve patient care and laboratory operations.

Partial Splenic Embolization in Paediatric Sickle Cell Disease Patients with Hypersplenism.

PURPOSE: To assess the safety and efficacy of partial splenic embolization (PSE) to reduce the need of transfusions and improve hematologic parameters in patients with hypersplenism and sickle cell disease (SCD). MATERIAL AND METHODS: This prospective study includes 35 homozygous hemoglobin S patients with SCD and hypersplenism who underwent PSE from 2015 until 2021 in Kinshasa. Patients were evaluated, before and after PSE (1, 3 and 6 months), using clinical, laboratory and ultrasonographic methods. PSE was performed with the administration of gelatin sponge particles embolizing 60-70% of the splenic parenchyma. RESULTS: The mean age was 10 (± 4) years and (21/35, 60%) were male. After PSE Leucocytes decreased at 3 months (16 692.94 vs 13 582.86, p = 0.02) and at six months Erythrocytes increased 2 004 000 vs. 2 804 142 (p < 0.001), Platelets increased (168 147 vs. 308 445, p < 0.001) and Hemoglobin increased (5.05 g/dL vs. 6.31 g/dL, p < 0.001) There was a significant dicrease in the need of transfusions from 6 (2-20) before PSE to 0.06 (0-1) after PSE (p < 0.001). The most frequent complication was splenic rupture (4/35, 11.4%), seen only and in all patients with hypoechogenic nodules at baseline. CONCLUSION: PSE is a safe procedure in patients with SCD and hypersplenism, that do not have hypoechogenic nodules in the spleen. PSE improves the hematological parameters and reduces the frequency of blood transfusions.

Healthy blood, healthy brain: a window into understanding and treating neurodegenerative diseases.

Our limited understanding of complex neurodegenerative disorders has held us back on the development of efficient therapies. While several approaches are currently being considered, it is still unclear what will be most successful. Among the latest and more novel ideas, the concept of blood or plasma transfusion from young healthy donors to diseased patients is gaining momentum and attracting attention beyond the scientific arena. While young or healthy blood is enriched with protective and restorative components, blood from older subjects may accumulate neurotoxic agents or be impoverished of beneficial factors. In this commentary, we present an overview of the compelling evidence collected in various animal models of brain diseases (e.g., Alzheimer, Parkinson, Huntington) to the actual clinical trials that have been conducted to test the validity of blood-related treatments in neurodegenerative diseases and argue in favor of such approach.

Analyzing and modeling massive transfusion strategies and the role of fibrinogen-How much is the patient actually receiving?

BACKGROUND: Hemorrhage is a leading cause of preventable death in trauma, cardiac surgery, liver transplant, and childbirth. While emphasis on protocolization and ratio of blood product transfusion improves ability to treat hemorrhage rapidly, tools to facilitate understanding of the overall content of a specific transfusion strategy are lacking. Medical modeling can provide insights into where deficits in treatment could arise and key areas for clinical study. By using a transfusion model to gain insight into the aggregate content of massive transfusion protocols (MTPs), clinicians can optimize protocols and create opportunities for future studies of precision transfusion medicine in hemorrhage treatment. METHODS: The transfusion model describes the individual round and aggregate content provided by four rounds of MTP, illustrating that the total content of blood elements and coagulation factor changes over time, independent of the patient's condition. The configurable model calculates the aggregate hematocrit, platelet concentration, percent volume plasma, total grams and concentration of citrate, percent volume anticoagulant and additive solution, and concentration of clotting factors: fibrinogen, factor XIII, factor VIII, and von Willebrand factor, provided by the MTP strategy. RESULTS: Transfusion strategies based on a 1:1:1 or whole blood foundation provide between 13.7 and 17.2 L of blood products over four rounds. Content of strategies varies widely across all measurements based on base strategy and addition of concentrated sources of fibrinogen and other key clotting factors. DISCUSSION: Differences observed between modeled transfusion strategies provide key insights into potential opportunities to provide patients with precision transfusion strategy.

The first two years of the use of low titer group O whole blood during French Military overseas operations: A retrospective study.

BACKGROUND: On the battlefield, hemorrhage is the main cause of potentially preventable death. To reduce mortality due to hemorrhagic injuries, the French Military Medical Service (FMMS) has deployed low titer group O whole blood (LTOWB) since June 2021 during operation BARKHANE in the Sahel-Saharan strip. Questions persist regarding the circumstances under which the FMMS employs LTOWB during overseas operations. STUDY DESIGN: We performed a retrospective analysis of all LTOWB transfused by the FMMS during overseas operations in the Sahel-Saharan strip between June 1, 2021, and June 1, 2023. Information was collected from battlefield forward transfusion sheets. RESULTS: Over the 2-year study period, 40 units of LTOWB were transfused into 25 patients. Of the 25 patients, 18 were combat casualties and seven were transfused for non-trauma surgery. Of the 40 units of LTOWB transfused, 22 were provided during Role 2 care, 11 during tactical medical evacuation (MEDEVAC), and seven in light and mobile surgical units. Among combat casualties, LTOWB was the first blood product transfused in 13 patients. In combat casualties, 6 h post-trauma, the median ratio of plasma: red blood cells (RBCs) was 1.5, and the median equivalent platelet concentrate (PC) transfused was 0.17. No immediate adverse events related to LTOWB transfusion were reported. CONCLUSION: LTOWB is transfused by the FMMS during overseas operations from the tactical MEDEVAC until Role 2 care. Deployment of LTOWB by the FMMS enables an early high-ratio plasma/RBC transfusion and an early platelet transfusion for combat casualties.

The expanding role of blood and tissue establishments in the development of advanced therapy medicinal products.

BACKGROUND AIMS: The relationship between blood establishments and advanced cellular therapies is evident in several European countries, with some involved in research and development and/or in manufacturing. The aim of the present study was to understand the advanced therapy medicinal product (ATMP) infrastructural, regulatory and logistic requirements needed for the Irish Blood Transfusion Service to support advanced therapeutics in Ireland. METHODS: An online survey consisting of 13 questions was distributed in a targeted manner to the identified ATMP stakeholders in Ireland, namely those working in industry, health care, regulatory agencies or education. Subject matter experts in the field were approached and interviewed to gain further insight into the relationship between blood and tissue establishments (BTEs) and ATMPs, to explore the advantages these institutions have in development and to highlight potential challenges for implementation. RESULTS: In total, 84.9% of survey respondents stated that BTEs have a role in the development of advanced therapeutics. Key BTE services identified as applicable to the ATMP sector from both surveys and interviews include the provision of starting materials for research and manufacturing, donor management, use of existing quality and traceability frameworks, product logistic strategies and Good Manufacturing Practice. Challenges for BTE expansion into the sector currently include high costs associated with ATMPs, lack of expertise in these therapies, limited therapeutic populations and no national ATMP strategic plan for Ireland. CONCLUSIONS: Blood establishments have services and expertise that can be extended into the advanced therapy sector. The existing knowledge and skill base of BTEs in Ireland should be leveraged to accelerate the development of ATMP strategies for industry and healthcare.

A novel measure to summarize blood transfusion practice during critical illness.

BACKGROUND: Large-scale observational studies have summarized transfusion practice using traditional measures of central tendency (e.g., the mean hemoglobin concentration at the time of transfusion). However, the mean hemoglobin concentration fails to identify specific hemoglobin concentration thresholds that drive practice. In the following brief report, we propose a novel measure of "practice discontinuity" that identifies specific practice-defining hemoglobin thresholds. STUDY DESIGN AND METHODS: We used the PINC AI Database (2016-2022) to identify adult patients admitted to an intensive care unit with at least one hemoglobin concentration measurement. For each day that hemoglobin was measured, we identified whether the patient received a red blood cell transfusion using hospital charge codes. We defined the "practice discontinuity" measure as the hemoglobin concentration at which there was the largest increase in transfusion use going from a higher to an incrementally lower hemoglobin concentration. We also calculated the mean and median pretransfusion hemoglobin concentrations. RESULTS: We identified 1,298,367 patients and 4,905,839 patient-days for inclusion. RBC transfusion occurred in a total of 530,654 (10.8%) patient-days. The overall pre-transfusion mean and median hemoglobin concentrations were 8.4 and 8.0 g/dL, respectively. The practice discontinuity measure identified 7.0 g/dL as the hemoglobin concentration at which transfusion use increased the most, from 46.6% of patient-days at a concentration of 7.0 g/dL to 74.8% of patient-days at a concentration of 6.9 g/dL. DISCUSSION: We propose that future studies of red blood cell transfusion practice consider inclusion of the practice discontinuity measure to more fully summarize clinical practice.

Transfusion safety: Is there a difference between reported reactions in low-to-middle income and high-income countries?

BACKGROUND AND OBJECTIVES: Transfusion safety may be becoming dependent on the financial resources made available for transfusion structures and may vary between high-income countries (HIC) and low-to-middle-income countries (LMIC). To assess whether there is a difference in the reported TR between these two groups of countries, we examined TR reported in Tunis the capital of Tunisia, a LMIC, and compared their frequency with reported TR in HIC. MATERIALS AND METHODS: Data of TR were collected from transfusion incident report (TIR) forms declared by healthcare facilities in Tunis between 2015 and 2019. They were analysed and compared to reported TR in France (ANSM) and UK (SHOT). RESULTS: The incidence of TR was 70.6/100 000 blood components (BP) issued. A third of TR (36.8%) occurred at night. Febrile non-hemolytic transfusion reactions (43.7%) and allergic reactions (35%) were the most reported TR respectively 22.4/100 000 BP and 17.9/100 000 BP. The rate of ABO incompatibilities was 1.96/100 000 red blood cell units (RBC): they were all caused by human error. The rates of TRALI, TACO and bacterial contaminations were respectively 1.26/100 000 BP, 1.4/100 000 RBC and 0.7/100 000 BP. CONCLUSION: While advanced technologies applied to transfusion have improved transfusion safety, this study shows that their impact has been relatively minor, as reported TR in LMIC are still comparable to those in HIC. ABO-incompatibilities are still higher in LMIC: this should be addressed by reinforcing the training of all healthcare personnel involved in transfusion medicine.

What's new in whole blood resuscitation? In the trauma bay and beyond.

PURPOSE OF REVIEW: Transfusion therapy commonly supports patient care during life-threatening injury and critical illness. Herein we examine the recent resurgence of whole blood (WB) resuscitation for patients in hemorrhagic shock following trauma and other causes of severe bleeding. RECENT FINDINGS: A growing body of literature supports the use of various forms of WB for hemostatic resuscitation in military and civilian trauma practice. Different types of WB include warm fresh whole blood (FWB) principally used in the military and low titer O cold stored whole blood (LTOWB) used in a variety of military and civilian settings. Incorporating WB initial resuscitation alongside subsequent component therapy reduces aggregate blood product utilization and improves early mortality without adversely impacting intensive care unit length of stay or infection rate. Applications outside the trauma bay include prehospital WB and use in patients with nontraumatic hemorrhagic shock. SUMMARY: Whole blood may be transfused as FWB or LTOWB to support a hemostatic approach to hemorrhagic shock management. Although the bulk of WB resuscitation literature has appropriately focused on hemorrhagic shock following injury, extension to other etiologies of severe hemorrhage will benefit from focused inquiry to address cost, efficacy, approach, and patient-centered outcomes.

Performance Improvement Program Review of Institutional Massive Transfusion Protocol Adherence: An Opportunity for Improvement.

BACKGROUND: Given the acuity of patients who receive MTPs and the resources they require, MTPs are a compelling target for performance improvement. This study evaluated adherence with our MTP's plasma:red blood cell ratio (FFPR) of 1:2 and platelet:red blood cell ratio (PLTR) of 1:12, to test the hypothesis that ratio adherence is associated with lower inpatient mortality. MATERIALS AND METHODS: The registry of an urban level I trauma center was queried for adult patients who received at least 6 units of packed red blood cells within 4 hours of presentation. Patients were excluded for interfacility transfer, cardiac arrest during the prehospital phase or within one hour of arrival, or for head AIS ≥5. Univariate analysis and multiple logistic regressions were performed to identify variables associated with early transfusion protocol noncompliance and the effect on inpatient mortality. RESULTS: Three hundred and eighty-three patients were included, with mean ISS of 25.9 ± 13.3 and inpatient mortality of 28.5%. Increasing age, ISS, INR, and total units of blood product transfused were associated with increased odds of mortality, while an increase in revised trauma score was associated with a decreased odds ratio of mortality. Achieving our goal ratios were protective against mortality, with OR of .451 (P = .013) and .402 (P=.003), respectively. DISCUSSION: Large proportions of critically injured patients were transfused fewer units of plasma and platelets than our MTP dictated; failure to achieve intended ratios at 4 hours was strongly associated with inpatient mortality. MTP processes and outcomes should be critically assessed on a regular basis as part of a mature performance improvement program to ensure protocol adherence and optimal patient outcome.