Karl Landsteiner (1868-1943): A Versatile Blood Scientist.

Karl Landsteiner (1868-1943) was an Austrian-American biologist, physician, and immunologist whose groundbreaking discoveries revolutionized the fields of transfusion medicine, immunology, and virology. His most famous work was the identification of the ABO blood group system in 1901, which explained the causes of transfusion reactions and laid the foundation for safe blood transfusions. This discovery earned him the Nobel Prize in Physiology or Medicine in 1930. Landsteiner continued his research, identifying the MN and P blood group system in 1927 and the Rh blood group system in 1940, which addressed the complexities of the Hemolytic Disease of the Fetus and Newborn (HDFN). His work on the poliovirus in 1908, in collaboration with Erwin Popper, established the infectious nature of the disease and laid the groundwork for future vaccine development. Landsteiner's versatility as a scientist is evident in the breadth of his work, spanning hematology, immunology, and virology. His ability to navigate diverse fields and see connections between them allowed him to make pioneering discoveries that have had a lasting impact on medical practice, particularly in blood transfusion, organ transplantation, and immunotherapy. Landsteiner's legacy as the "Father of Transfusion Medicine" is reinforced by the standardization of blood typing procedures, which have saved millions of lives worldwide.

From Transfusion Medicine to Vaccines: The Enduring Impact of Karl Landsteiner.

This is the biography of the Nobel Prize winner Karl Landsteiner who divided human blood into groups according to the presence of naturally occurring agglutinating antibodies. His research eventually led to the establishment of safe transfusion practices. Before his discovery, transfusions of blood were given to patients in need from animals like sheep or randomly chosen human donors, often with disastrous results. Millions of lives were genuinely saved by Landsteiner's discovery. He established the foundation for the creation of the polio vaccine by determining that a microbe causes poliomyelitis. Additionally, Landsteiner contributed to the identification of the syphilis-causing microbes. This biography is a tribute to the legend Karl Landsteiner.

Do Babesia microti Hosts Share a Blood Group System Gene Ortholog, Which Could Generate an Erythrocyte Antigen That Is Essential for Parasite Invasion?

The United States of America (US) has the highest annual number of human babesiosis cases caused by Babesia microti (Bm). Babesia, like malaria-causing Plasmodium, are protozoan parasites that live within red blood cells (RBCs). Both infectious diseases can be associated with hemolysis and organ damage, which can be fatal. Since babesiosis was made a nationally notifiable condition by the Centers for Disease Control and Prevention (CDC) in January 2011, human cases have increased, and drug-resistant strains have been identified. Both the Bm ligand(s) and RBC receptor(s) needed for invasion are unknown, partly because of the difficulty of developing a continuous in vitro culture system. Invasion pathways are relevant for therapies (e.g., RBC exchange) and vaccines. We hypothesize that there is at least one RBC surface antigen that is essential for Bm invasion and that all Bm hosts express this. Because most RBC surface antigens that impact Plasmodium invasion are in human blood group (hBG) systems, which are generated by 51 genes, they were the focus of this study. More than 600 animals with at least one hBG system gene ortholog were identified using the National Center for Biotechnology Information (NCBI) command-line tools. Google Scholar searches were performed to determine which of these animals are susceptible to Bm infection. The literature review revealed 28 Bm non-human hosts (NHH). For 5/51 (9.8%) hBG system genes (e.g., RhD), no NHH had orthologs. This means that RhD is unlikely to be an essential receptor for invasion. For 24/51 (47.1%) hBG system genes, NHH had 4-27 orthologs. For the ABO gene, 15/28 NHH had an ortholog, meaning that this gene is also unlikely to generate an RBC antigen, which is essential for Bm invasion. Our prior research showed that persons with blood type A, B, AB, O, RhD+, and RhD- can all be infected with Bm, supporting our current study's predictions. For 22/51 (43.1%) hBG system genes, orthologs were found in all 28 NHH. Nineteen (37.3%) of these genes encode RBC surface proteins, meaning they are good candidates for generating a receptor needed for Bm invasion. In vitro cultures of Bm, experimental Bm infection of transgenic mice (e.g., a CD44 KO strain), and analyses of Bm patients can reveal further clues as to which RBC antigens may be essential for invasion.

Anemia and Transfusion Medicine.

Peri-operative anemia is a common condition encountered in adult surgical patients. It is increasingly recognized as a predictor of post-operative morbidity and mortality. Evaluation and treatment of anemia pre-operatively can reduce transfusion needs and potentially improve outcomes in surgical patients. This article discusses anemia optimization strategies in peri-operative setting with special focus on use of intravenous iron therapy. Additionally, the authors describe the role of transfusion medicine and best practices around red blood cell, platelet, and plasma transfusions.

Evaluation of the dog population in two Italian shelters in Central Italy (Marche region) as potential blood donors.

Background: In recent years, the field of transfusion medicine for dogs has advanced significantly, becoming a crucial aspect of veterinary clinical practice. Nowadays, blood still remains a fundamental biological source and the welfare and health status of eligible species-specific blood donors are essential for veterinary transfusion medicine. Aim: This study focused on evaluating two shelters in Central Italy (Marche region), located in Tolentino (TS) and in Camerino (CS), in order to assess the potential of the shelter dogs as canine blood donors. Methods: We evaluated a total of 45 dogs from these shelters based on physical (age and size), clinical, behavioural, and blood analysis criteria described in the Italian Ministerial Guideline for Veterinary Transfusion Medicine (2016). Results: At the TS shelter, out of 206 resident dogs, 125 met the donation criteria (60.68%), with 28 (13.59%) selected for the study due to the impossibility to collect the samplings or other exclusion causes. In the CS shelter, of the 149 dogs, 17 (11.41%) were identified as potential blood donors and included in the study. Among these, seven dogs (25%) from TS and five dogs (29.41%) from CS were found to have DEA1 negative blood group. High percentages (TS = 25.24%, CS = 40.27%) of dogs were excluded for seniority and 29.53% in CS for behavioural issues. Notable findings included reduced erythrocyte mean corpuscular volume [mean TS = 63.93 fl; CS = 64.00 fl] and Reticulocyte Hemoglobin [mean TS = 22.39 pg; CS = 21.38 pg]. Additionally, in both shelters' dogs showed a modest increase in eosinophils levels [mean TS = 1.59 K/µl; CS = 1.02 K/µl]. Conclusion: Shelter dogs can fulfill the blood donation requirements set by the Italian Ministerial Guideline on Veterinary Transfusion Medicine. They are generally in good health and present a low risk of transmitting parasitic diseases; however, many are ineligible for donation due to behavioural pathologies or temperament issues and seniority.

Impact of immunoglobulin preparations on anti-HLA antibody specificity analysis.

BACKGROUND: Donor-specific antibodies (DSAs) targeting human leukocyte antigens (HLAs) substantially reduce the longevity of transplanted organs. Desensitization of DSA-positive renal transplant recipients is achieved through intravenous administration of immunoglobulin (IVIg). However, the presence and detectability of anti-HLA antibodies in IVIg preparations following administration are not fully understood. We aimed to assess whether immunoglobulin preparations contain anti-HLA antibodies that can be detected as passive antibodies when administered into the body. METHODS: We evaluated 3 immunoglobulin preparations from different pharmaceutical companies, using anti-HLA class I and II antibody specificity tests and immunocomplex capture fluorescence analysis (ICFA). RESULTS: Direct testing for anti-HLA antibodies resulted in high background errors, particularly for Venoglobulin. Diluting Venoglobulin to physiological concentrations revealed the presence of anti-HLA class I antibodies; however, no common alleles were found between the specificity identification test and ICFA.For Glovenin and Venilon, anti-HLA class I and II antibodies were detected; however, variability was observed across different test reagent lots. Moreover, dilution of the globulin formulation revealed a prozone phenomenon. CONCLUSION: The administration of IVIg complicates the accurate detection of anti-HLA antibodies, underscoring the need for careful interpretation of test results post-IVIg administration.

Harnessing the potential of red blood cells in immunotherapy.

Red blood cell (RBC) transfusion represents one of the earliest and most widespread forms of cellular therapy. While the primary purpose of RBC transfusions is to enhance the oxygen-carrying capacity of the recipient, RBCs also possess unique properties that make them attractive vehicles for inducing antigen-specific immune tolerance. Preclinical studies have demonstrated that RBC transfusion alone, in the absence of inflammatory stimuli, often fails to elicit detectable alloantibody formation against model RBC antigens. Several studies also suggest that RBC transfusion without inflammation may not only fail to generate a detectable alloantibody response but can also induce a state of antigen-specific non-responsiveness, a phenomenon potentially influenced by the density of the corresponding RBC alloantigen. The unique properties of RBCs, including their inability to divide and their stable surface antigen expression, make them attractive platforms for displaying exogenous antigens with the goal of leveraging their ability to induce antigen-specific non-responsiveness. This could facilitate antigen presentation to the host's immune system without triggering innate immune activation, potentially enabling the induction of antigen-specific tolerance for therapeutic applications in autoimmune disorders, preventing immune responses against protein therapeutics, or reducing alloreactivity in the setting of transfusion and transplantation.

The practical use of artificial intelligence in Transfusion Medicine and Apheresis.

BACKGROUND: Blood and plasma volume calculations are a daily part of practice for many Transfusion Medicine and Apheresis practitioners. Though many formulas exist, each facility may have their own modifications to consider. ChatGPT (Generative Pre-trained Transformer) provides a new and exciting pathway for those with no programming experience to create personalized programs to meet the demands of daily practice. Additionally, this pathway creates computer programs that provide accurate and reproducible outputs. Herein, we aimed to create a step-by-step process for clinicians to create customized computer programs for use in everyday practice. METHODS: We created a process of inputs to ChatGPT-40, which generated computer programming code. This code was copied and pasted into Notepad (and saved as a Python file) and Google Colaboratory to verify functionality. We validated the durability of our process by repeating it over a 5-day timeframe and by recruiting volunteers to reproduce our outputs using the suggested process. RESULTS: Computer code generated by ChatGPT-40 in response to our common language inputs was accurate and durable over time. The code was fully functional in both Python and Colaboratory. Volunteers reproduced our process and outputs with minimal assistance. CONCLUSION: We analyzed the practical application of ChatGPT-40 and artificial intelligence (AI) to perform daily calculations encountered in Transfusion Medicine. Our results provide a proof of concept that people with no programming experience can create customizable solutions for their own facilities. Our future work will expand to the creation of comprehensive and customizable websites designed for each individual user.

Blood bank quality control: pH assessment methods in platelet concentrates.

Platelet concentrates undergo progressive changes during storage, such as a decrease in pH. Additionally, pH and lactate production showed the strongest correlation with platelet survival in posttransfusion viability studies. pH measurement is a straightforward method for evaluating the quality control of blood components in blood bank practice. Our aim was to compare three pH assessment methods for canine platelet concentrates. The pH values of the canine platelet concentrates were assessed on the first day of storage using a calibrated pH meter, a portable gas analyzer and pH-indicator strips. The results from the pH meter and portable gas analyzer measurements were similar. The pH indicator strips presented higher average values compared to the other more reliable methods evaluated, which could result in the use of inadequate blood components. In conclusion, it is recommended to implement pH measurements using a pH meter for quality control in veterinary blood banks.

Survey of pediatric massive transfusion protocol practice at United States level I trauma centers: An AABB Pediatric Transfusion Medicine Subsection study.

BACKGROUND: Trauma remains the leading cause of pediatric mortality in the United States. Although use of massive transfusion protocols (MTPs) in this population is widespread, optimal pediatric resuscitation is not well established. We sought to assess contemporary pediatric MTP practice in the United States. STUDY DESIGN AND METHODS: A web-based survey was designed by the Association for the Advancement of Blood & Biotherapies (AABB) Pediatric Transfusion Medicine Subsection and distributed to select American College of Surgeons (ACS) Level I Verified pediatric trauma centers. The survey assessed current MTP policy, implementation, and recent changes in practice. RESULTS: Response rate was 55% (22/40). Almost half of the respondents were from the South. The median RBC:plasma ratio was 1 (interquartile range 1-1.5). Protocolized fibrinogen supplementation was common while integration of antifibrinolytic therapy into MTPs was infrequent. Viscoelastic testing (VET) was available at most sites, 71% (15/21, one site did not respond), and was generally utilized on an ad-hoc basis. Roughly, a third of sites had changed their MTP in the past 3 years due to blood supply issues, and about a third reported having group O Whole Blood on-site. CONCLUSION: MTP practice is similar throughout the United States. Though fibrinogen supplementation is common-other emerging interventions such as antifibrinolytic therapy or utilization of routine viscoelastic testing-are not widespread. Pediatric transfusion medicine experts must continue to follow practice change, as contemporary large trials begin to characterize new supportive modalities to optimize resuscitation in pediatric trauma patients.

Analysis of emergency resuscitative thoracotomy in the combat setting.

INTRODUCTION: Emergency resuscitative thoracotomy (ERT) is a resource-intensive procedure that can deplete a combat surgical team's supply and divert attention from casualties with more survivable injuries. An understanding of survival after ERT in the combat trauma population will inform surgical decision-making. METHODS: We requested all encounters from 2007 to 2023 from the Department of Defense Trauma Registry (DoDTR). We analysed any documented thoracotomy in the emergency department and excluded any case for which it was not possible to distinguish ERT from operating room thoracotomy. The primary outcome was 24-hour mortality. RESULTS: There were 48 301 casualties within the original dataset. Of those, 154 (0.3%) received ERT, with 114 non-survivors and 40 survivors at 24 hours. There were 26 (17%) survivors at 30 days. The majority were performed in role 3. The US military made up the largest proportion among the non-survivors and survivors. Explosives predominated in both groups (61% and 65%). Median Composite Injury Severity Scores were lower among the non-survivors (19 vs 33). Non-survivors had a lower proportion of serious head injuries (13% vs 40%) and thorax injuries (32% vs 58%). Median RBC consumption was lower among non-survivors (10 units vs 19 units), as was plasma (6 vs 16) and platelets (0 vs 3). The most frequent interventions and surgical procedures were exploratory thoracotomy (n=140), chest thoracostomy (n=137), open cardiac massage (n=131) and closed cardiac massage (n=121). CONCLUSION: ERT in this group of combat casualties resulted in 26% survival at 24 hours. Although this proportion is higher than that reported in civilian data, more rigorous prospective studies would need to be conducted or improvement in the DoDTR data capture methods would need to be implemented to determine the utility of ERT in combat populations.

Protocol for a phase 3, randomised, active-control study of four-factor prothrombin complex concentrate versus frozen plasma in bleeding adult cardiac surgery patients requiring coagulation factor replacement: the LEX-211 (FARES-II) trial.

INTRODUCTION: Reduced thrombin generation is an important component of post cardiopulmonary bypass (CPB) coagulopathy. To replenish coagulation factors and enhance thrombin generation in bleeding surgical patients, frozen plasma (FP) and four-factor prothrombin complex concentrate (4F-PCC) are used. However, the efficacy-safety balance of 4F-PCC relative to FP in cardiac surgery is unconfirmed. METHODS AND ANALYSIS: LEX-211 (FARES-II) is an active-control, randomised, phase 3 study comparing two coagulation factor replacement therapies in bleeding adult cardiac surgical patients at 12 hospitals in Canada and the USA. The primary objective is to determine whether 4F-PCC (Octaplex/Balfaxar, Octapharma) is clinically non-inferior to FP for haemostatic effectiveness. Inclusion criteria are any index (elective or non-elective) cardiac surgery employing CPB and coagulation factor replacement with 4F-PCC or FP ordered in the operating room for bleeding management. Patients will be randomised to receive 1500 or 2000 international units of 4F-PCC or 3 or 4 units of FP, depending on body weight. The primary endpoint of haemostatic treatment response is 'effective' if no additional haemostatic intervention is required from 60 min to 24 hours after the first initiation of 4F-PCC or FP; or 'ineffective' if any other haemostatic intervention (including a second dose of study drug) is required. An estimated 410 evaluable patients will be required to demonstrate non-inferiority (one-sided α of 0.025, power ≥90%, non-inferiority margin 0.10). Secondary outcomes include transfusions, bleeding-related clinical endpoints, coagulation parameters and safety. ETHICS AND DISSEMINATION: The trial has been approved by the institutional review boards of all participating centres. Trial completion is anticipated at the end of 2024, and results will be disseminated via publications in peer-reviewed journals and conference presentations in 2025. The results will advance our understanding of coagulation management in bleeding surgical patients, potentially reducing the need for allogeneic blood products and improving outcomes in surgical patients. TRIAL REGISTRATION NUMBER: NCT05523297.

Evaluation of the LightCycler® PRO Instrument as a Platform for Rhesus D Typing.

Rapid and reliable Rhesus D typing is crucial for blood donation centers. In instances of massive blood transfusion or reduced antigen expression, DNA-based phenotype prediction becomes mandatory. Our molecular RHD typing approach involves an initial real-time PCR for the most common aberrant RHD types in our region, RHD*01W.1 (weak D type 1), RHD*01W.2 (weak D type 2), RHD*01W.3 (weak D type 3), and RHD*07.01 (DVII). For comprehensive coverage, Sanger sequencing of RHD coding regions is performed in the case of PCR target-negative results. We evaluated the specificity and accuracy of these methods using the recently launched LightCycler® PRO real-time platform. All findings demonstrated remarkable accuracy. Notably, the LightCycler® PRO instrument offers a distinct advantage in data interpretation and integration via the HL7 interface. This study underlines the importance of including advanced molecular techniques in blood typing protocols, especially in scenarios where conventional serological methods may be insufficient.

The effects of drone transportation on blood component quality: A prospective randomised controlled laboratory study.

The use of uncrewed aerial vehicles (drones) has increased over the last decade. However, their application in healthcare has not been fully examined, in part, due to regulations preventing flight beyond the visual line of sight. This prospective randomised controlled laboratory study aimed to determine whether the in vitro quality of packed red blood cell components is maintained when transported by drone, beyond visual line of sight. Ten identical pairs of packed red blood cell units were randomly allocated to transport by drone or by ground vehicle (1:1, allocation concealment) 68 km between two hospitals in Northumbria, UK. Markers of blood component quality were compared at 8, 14, 28 and 35 days following blood unit manufacture. There was no statistical difference in haemolysis, potassium concentration, total haemoglobin, glucose and lactate, haematocrit and mean cell volume, between the two groups, up to the date of unit expiry. The temperature of the packed red blood cell units did not deviate outside the recommended 2-10°C for transportation, regardless of the allocated group. Blood component transport was faster by drone, but did not reach statistical significance. This study demonstrates the feasibility and safety of flying blood components by drone between hospitals in the United Kingdom.

Comparing the effects of problem- and task-based learning on knowledge and clinical decision-making of nursing students concerning the use of transfusion medicine in pediatric nursing: An educational quasi-experimental study in Iran.

Background: In the pediatric care field, ensuring safe and effective blood transfusions, promptly identifying adverse reactions, and implementing appropriate interventions are crucial. Therefore, undergraduate nursing curricula need to be structured to meet these professional standards and prepare nursing students, as future team members, to respond to relevant clinical situations. The objective of this study was to investigate how problem- and task-based learning affects knowledge and clinical decision-making of undergraduate nursing students concerning the use of transfusion medicine in pediatric nursing. Material and methods: This quasi-experimental study involved 82 nursing students recruited from two nursing schools in Iran using convenience sampling. Participants received educational content through either problem- (n = 40) or task-based learning (n = 42) methods. A researcher-made tool, comprising three parts and proven to be valid and reliable, was utilized for data collection. The tool was administered both before and immediately after the intervention. Data were analyzed using Wilcoxon rank-sum, Mann-Whitney U, Spearman's correlation and multivariate analysis of covariance tests via SPSS v16.0. A p-value of <0.05 was considered significant for all tests. Results: The median post-test knowledge and clinical decision-making scores within problem- and task-based learning groups were 62.68 vs. 74.65 and 53.33 vs. 76.67, respectively. Significant differences were observed between the mean pre- and post-test scores of both variables within both intervention groups (p < 0.05). Multivariate analysis of covariance revealed that task-based learning resulted in significant differences between the two groups in terms of knowledge (F = 87.9 %, p = 0.002, Eta2 = 0.114) and clinical decision-making (F = 99.9 %, p < 0.001, Eta2 = 0.271). Conclusions: Given the greater effectiveness of task-based learning, nursing schools are advised to utilize this method in undergraduate nursing curricula to ensure the adequacy of the clinical skills acquired by nursing students prior to graduation.

Analysis of the effect and influencing factors of a clinical competency-oriented prospective pre-job training programme on the comprehensive ability of new employees in the department of transfusion medicine.

BACKGROUND: The subject of pre-job training for transfusion service laboratory technicians is very important. The key is how to make a reasonable systematic training programme to improve the effectiveness of training. METHODS: A prospective training programme was conducted and an assessment was performed at enrollment (baseline) and reassessment after 3-months training, using the same tools with a validated questionnaire. RESULTS: Clinical competency-oriented prospective pre-job training significantly improves the clinical transfusion-related comprehensive skills of new employees. The post-training assessment score was significantly affected by undergraduate major. CONCLUSION: This study provided a clinical competency-oriented training programme for new employees in the department of transfusion medicine that could effectively enhance their comprehensive abilities.

"Something we must be proud of": An interview and document study of team improvisation in the Dutch convalescent plasma project group.

Background and Aims: The COVID-19 pandemic has revealed the importance of organizational resilience, the ability to effectively respond to a disruptive event before, during, and after it occurs. Team improvisation is an important component of organizational resilience as it describes characteristics of team skills and contextual qualities to create order from chaos. In Spring 2020, the Dutch national blood bank, began the convalescent plasma project (CCP). We aimed to study which elements of team improvisation in the CCP group were found and how lessons learned can contribute towards a non-crisis situation for blood establishments. Methods: Using Vera and Crossan's framework of improvisation, semi-structured interviews with eight members of the CCP group were conducted. This was simultaneous to performing a document analysis of 21 Intranet posts and seven internal reports. MAXDA 2020 was used to conduct deductive and inductive thematic analyses. Results: The CCP group showed strong characteristics of expertise and memory, teamwork quality, experimental culture, and real-time information and communication that enabled them to improvise in all aspects of the donation process. Improvisation examples included comprehensive communication methods to identify and obtain new donors, asking additional intake questions and collecting additional aliquots to store while waiting for an internal antibody test to be developed, and regulatory respondents allowing a flexible change control procedure to meet the pace of the crisis. Training was evident to a lesser degree. Conclusion: While improvisation impacted set routines and procedures, the safety and quality of the product were not affected. Regarding organizational resilience, our results showed that the CCP group "coped" well using elements of team improvisation. Blood establishments may consider introducing improvisational training and innovation teams throughout the organization for future preparedness and improving organizational resilience.