Battle of the (Chat)Bots: Comparing Large Language Models to Practice Guidelines for Transfusion-Associated Graft-Versus-Host Disease Prevention.

Published guidelines and clinical practices vary when defining indications for irradiation of blood components for the prevention of transfusion-associated graft-versus-host disease (TA-GVHD). This study assessed irradiation indication lists generated by multiple artificial intelligence (AI) programs, or chatbots, and compared them to 2020 British Society for Haematology (BSH) practice guidelines. Four chatbots (ChatGPT-3.5, ChatGPT-4, Bard, and Bing Chat) were prompted to list the indications for irradiation to prevent TA-GVHD. Responses were graded for concordance with BSH guidelines. Chatbot response length, discrepancies, and omissions were noted. Chatbot responses differed, but all were relevant, short in length, generally more concordant than discordant with BSH guidelines, and roughly complete. They lacked several indications listed in BSH guidelines and notably differed in their irradiation eligibility criteria for fetuses and neonates. The chatbots variably listed erroneous indications for TA-GVHD prevention, such as patients receiving blood from a donor who is of a different race or ethnicity. This study demonstrates the potential use of generative AI for transfusion medicine and hematology topics but underscores the risk of chatbot medical misinformation. Further study of risk factors for TA-GVHD, as well as the applications of chatbots in transfusion medicine and hematology, is warranted.

Managing Sickle Cell Disease in Patients for Whom Blood Transfusion Is Not an Option.

Sickle Cell Disease (SCD) is a hereditary blood disorder affecting beta hemoglobin. This disorder causes sickle-shaped red blood cells with decreased oxygen-carrying capacity resulting in vaso-occlusive crises. These crises are often treated with analgesics, antibiotics, IV fluids, supplementary oxygen, and allogeneic blood transfusion. This treatment regimen becomes complicated when caring for SCD patients for whom blood transfusion is not an option. Blood transfusion may not be an option due to the patient's religious, personal, or medical concerns and in scenarios where blood is not available for transfusion. Some examples include the patient being a Jehovah's Witness, blood-borne pathogens concerns, or prior history of multiple alloantibodies and severe transfusion reactions. The number of patients in these categories is growing. The patients and their autonomy should be respected during treatment. This review focuses on the currently available modalities to best manage this subgroup of SCD patients without blood transfusion, including new professional guidelines and new therapies to reduce the severity of SCD as approved by the Food and Drug Administration since 2017.

Epidemiological and clinical features, therapeutic strategies and outcomes in patients with hyperhaemolysis: A systematic review.

Hyperhaemolysis syndrome (HHS), a severe form of delayed haemolytic transfusion reaction most commonly described in patients with sickle cell disease (SCD), involves destruction of both donor and recipient red blood cells (RBCs). As the epidemiology and underlying pathophysiology have yet to be definitively elucidated, recognition can be challenging. We systematically reviewed PubMed and EMBASE to identify all cases of post-transfusion hyperhaemolysis and characterized the epidemiological, clinical and immunohaematological characteristics and treatments of HHS. We identified 51 patients (33 females and 18 males), including 31 patients with SCD (HbSS, HbSC and HbS/ß-thalassaemia). The median haemoglobin nadir (3.9 g/dL) occurred a median of 10 days post-transfusion. 32.6% and 45.7% of patients had a negative indirect anti-globulin test and a negative direct anti-globulin test, respectively. The most common therapies included corticosteroids and intravenous immune globulin. 66.0% of patients received ≥1 supportive transfusion, which was associated with a longer median hospital stay/time to recovery (23 days vs. 15 days; p = 0.015) compared to no supportive transfusion. These findings illustrate that HHS that often results in marked anaemia 10 days post-transfusion is not restricted to patients with haemoglobinopathies, and additional transfused RBCs may be associated with a longer time-to-recovery.

Standardized reporting of pulmonary transfusion complications: Development of a model reporting form and flowchart.

BACKGROUND: Pulmonary complications of blood transfusion, including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and transfusion-associated dyspnea, are generally underdiagnosed and under-reported. The international TRALI and TACO definitions have recently been updated. Currently, no standardized pulmonary transfusion reaction reporting form exists and most of the hemovigilance forms have not yet incorporated the updated definitions. We developed a harmonized reporting form, aimed at improved data collection on pulmonary transfusion reactions for hemovigilance and research purposes by developing a standardized model reporting form and flowchart. MATERIALS AND METHODS: Using a modified Delphi method among an international, multidisciplinary panel of 24 hemovigilance experts, detailed recommendations were developed for a standardized model reporting form for pulmonary complications of blood transfusion. Two Delphi rounds, including scoring systems, took place and several subsequent meetings were held to discuss issues and obtain consensus. Additionally, a flowchart was developed incorporating recently published redefinitions of pulmonary transfusion reactions. RESULTS: In total, 17 participants completed the first questionnaire (70.8% response rate) and 14 participants completed the second questionnaire (58.3% response rate). According to the results from the questionnaires, the standardized model reporting form was divided into various subcategories: general information, patient history and transfusion characteristics, reaction details, investigations, treatment and supportive care, narrative, and transfused product. CONCLUSION: In this article, we present the recommendations from a global group of experts in the hemovigilance field. The standardized model reporting form and flowchart provide an initiative that may improve data collected to address pulmonary transfusion reactions.

Prehospital Use of Whole Blood for Ill and Injured Patients During Critical Care Transport.

OBJECTIVE: Hemodynamic instability and hemorrhagic shock are frequently encountered by emergency medical services providers managing ill and injured patients during critical care transport. Although many critical care transport services commonly transfuse crystalloids and/or packed red blood cells (PRBCs), the administration of whole blood (WB) in prehospital care is currently limited. WB contains PRBCs, plasma, and platelets in a physiologic ratio to aid in oxygen delivery to tissue as well as hemostasis. This study describes a single critical care transport program's experience using WB for critically ill and injured patients and reports important clinical and safety outcomes. METHODS: This study was a retrospective review of patients who were transported by a single rotor wing-based critical care transport service to 1 of 2 tertiary care receiving hospitals within a single health system. Patients who were transported between November 1, 2018, and November 30, 2019, and who received at least 1 unit of low-titer group O WB during critical care transport were included. The primary outcomes of interest included 24-hour mortality and the total 24-hour transfusion requirement. The safety outcomes included transfusion reactions, acute lung injury, acute kidney injury, and the incidence of venous thromboembolism. RESULTS: During the study period, there were 3,084 total patients transported by our critical care transport service. There were 71 patients who received prehospital WB, 64 of whom met the inclusion criteria. The top 3 indications for WB administration included blunt trauma (n = 27, 42.2%), gastrointestinal hemorrhage (n = 15, 23.4%), and penetrating trauma (n = 11, 17.2%). The median total number of blood components transfused within 24 hours was 4.0 (interquartile range, 2.0-9.5), and the overall 24-hour mortality rate was 21.9%. CONCLUSIONS: The administration of WB by emergency medical services providers to critically ill and injured patients in the prehospital setting is feasible and is associated with low incidences of adverse events and transfusion reactions. Further research is needed to elucidate the benefits of WB relative to current prehospital standards of care.

Adverse events of red blood cell transfusions in patients with sickle cell disease.

Blood transfusion is a common medical intervention for patients with sickle cell disease (SCD) and disease related complications. While patients with SCD are at risk for all transfusion related adverse events defined by the National Healthcare Safety Network (NHSN) Biovigilance Component Hemovigilance Module Surveillance Protocol, they are uniquely susceptible to certain adverse events. This review discusses risk factors, mitigation strategies, and management recommendations for alloimmunization, hemolytic transfusion reactions, hyperviscosity and transfusion-associated iron overload in the context of SCD.

Incidence and characteristics of hypotensive transfusion reaction: 10-year experience in a single center.

BACKGROUND: Hypotensive transfusion reaction (HyTR) is rare. It is characterized by a rapid onset of hypotension during transfusion, which usually resolves quickly upon cessation of transfusion. Information on the incidence and clinical characteristics of HyTR has been reported in only a few studies. STUDY DESIGN AND METHODS: We retrospectively reviewed HyTR cases from 10-year hemovigilance data in a tertiary care hospital in Seoul, Korea. RESULTS: We identified 37 HyTRs in 35 patients, and the overall incidence of HyTR was 0.50 per 10,000 transfused units. Among the blood components, the incidence of HyTR was highest in filtered random donor platelets (0.75 per 10,000 units). About half of the HyTRs occurred within 15 min after the start of transfusion (19/37). Blood pressure returned to the normal range within an hour in 73.0% of the cases (27/37). All HyTR cases recovered without severe complications. Known risk factors for HyTR were not prominent in our cohort of patients, with no patients taking angiotensin-converting enzyme inhibitors and only five patients transfused with bedside filtered platelets. DISCUSSION: HyTR can occur in patients with various conditions and types of blood components. Understanding the clinical characteristics of HyTR facilitates proper management, leading to improved transfusion safety.

Practice patterns of ABO-matching for cryoprecipitate and patient outcomes after ABO-compatible versus incompatible cryoprecipitate.

BACKGROUND AND OBJECTIVES: This sub-study of the FIBRES trial sought to examine the patterns of ABO-compatible cryoprecipitate administration and to identify adverse consequences of ABO-incompatible cryoprecipitate. MATERIALS AND METHODS: This was a post hoc analysis of data collected from the FIBRES randomized clinical trial comparing fibrinogen concentrate with cryoprecipitate in the treatment of bleeding related to hypofibrinogenemia after cardiac surgery. The primary outcome was the percentage of administered cryoprecipitate that was ABO-compatible. Secondary outcomes were adverse events at 28 days. A follow-up survey was distributed to the FIBRES participating sites to examine the rationale behind the identified cryoprecipitate ABO-matching practice patterns. RESULTS: A total of 363 patients were included: 53 (15%) received ABO-incompatible cryoprecipitate and 310 (85%) received ABO-compatible cryoprecipitate. There was an increased incidence of post-operative anaemia in the ABO-incompatible group (15; 28.3%) in comparison to the ABO-compatible (44; 14.2%) group (p = 0.01) at 28 days, which was unrelated to haemolysis, without a significant difference in transfusion requirement. In the multivariable logistic regression models accounting for clustering by site, there was no observed statistically significant association between the administration of ABO-incompatible cryoprecipitate and any other adverse outcomes. Nine out of 11 sites did not have a policy requiring ABO-matched cryoprecipitate. CONCLUSION: This sub-study demonstrated that most cryoprecipitate administered in practice is ABO-compatible, despite the absence of guidelines or blood bank policies to support this practice. A signal towards increased risk of post-operative anaemia may be explained by higher rates of urgent surgery (vs. elective) in the ABO-incompatible group. Future studies should prospectively examine the impact of ABO-compatible versus incompatible cryoprecipitate to conclusively establish if there is a meaningful clinical impact associated with the administration of ABO-incompatible cryoprecipitate.

[Gallstone complications in sickle cell patients]. / Complications lithiasiques chez les patients drépanocytaires.

Chronic haemolysis exposes patients with sickle cell disease (SCD) to the development of black pigment gallstones, which can trigger biliary complications. In order to avoid these complications, elective cholecystectomy is recommended in France for all SCD patients with detected gallstones. However, all surgeries, and especially abdominal surgeries, entail an increased risk of vaso-occlusive complications in the peri- and post-operative periods, the most dreadful one being the acute chest syndrome. Preoperative transfusion has been shown in several studies to reduce acute postoperative complications, but exposes the patient to definitive alloimmunization, or even delayed post- transfusion haemolysis, justifying a recent trend towards transfusion sparing. The conditions for avoiding transfusion for a simple and frequent surgery such as cholecystectomy are based on a benefit- risk balance, and must be discussed on a case-by-case basis by the SCD specialist. In particular, it seems fully justified to perform prophylactic preoperative transfusion in patients with a history of recent vaso-occlusive crisis or acute chest syndrome (within 6 months preoperatively), and those operated on in an emergency setting, who are particularly at risk of postoperative events.

Hypersensitivity transfusion reactions to fresh frozen plasma: a retrospective analysis of the French hemovigilance network.

Few data are currently available on hypersensitivity transfusion reactions (HTRs) after exposure to fresh frozen plasma (FFP). Between 2000 and 2018, three different FFP production strategies have been used in France, leading to the concomitant use of different types of FFP. The objective of this study was to describe the rate of FFP-related HTRs and to assess the relative risk of each type of FFP. HTR following FFP transfusion between 2000 and 2018 were retrospectively extracted from the national hemovigilance database of the French National Agency for Medicines and Health Products Safety (ANSM). Temporal evolution of the incidence of reactions was modeled using logistic regression. During the study period, the overall rate of FFP-related HTRs was 52.0 (95% CI 50.2-53.9) reactions per 100,000 units of FFP issued. The rate of FFP-related HTRs progressively increased over the study period, from 28.7 (95% CI 22.8-36.0) in 2000 to 88.9 (78.8-100.3) reactions per 100,000 units of FFP issued in 2018 (OR 1.08 [1.07 - 1.09], P < .001), whereas the rate of other types of adverse transfusion reactions (ATRs) decreased. Between 2000 and 2014, its period of use, Solvent-Detergent-treated Apheresis FFP (SD-APH) was associated with the lowest risk of HTR. Our results indicate that although the rate of HTRs to FFP is low in France, the risk of having such a reaction has steadily increased between 2000 and 2018. A declarative bias is unlikely as the rate of other type of FFP-related ATRs decreased over the same period. The risk of HTRs to FFP is suggested to differ according to the processing of the FFP with a lower risk for SD-APH.

[Delayed Hemolytic Transfusion Reaction after Mitral Valve Replacement:Report of a Case].

We report a case of delayed hemolytic transfusion reaction (DHTR) after mitral valve replacement (MVR). A 67-year-old woman with a history of blood transfusion( BT) was admitted for MVR. Preoperative laboratory test proved to be negative for irregular antibodies except anti-Dia. She underwent MVR using a mechanical prosthesis and compatible blood products were transfused perioperatively. On post-operative day 13, she developed hemoglobinuria and anemia with elevated serum total bilirubin and lactic dehydrogenase levels. Transesophageal echocardiography showed trivial transvalvular leakage. Laboratory test successfuly identified another irregular antibody, anti-Jkb antibody. The patient had Jkb negative BT and did not need re-operation. Later, she recovered with no signs of hemolysis. Since anti-Jkb antibody gets undetectable within a few months, it is difficult to find out before surgery. As hemolysis following cardiac surgery is more commonly associated with prostheses and extracorporeal circulation than DHTR. Physicians should, however, be aware of this unusual complication especially in patients who underwent BT.

Relationship between allergic transfusion reactions and allergic predisposition among pediatric patients with hematological/oncological disease.

BACKGROUND: Allergic transfusion reactions (ATRs) manifest frequently as transfusion reactions, and their onset may be related to a patient's allergic predisposition. Moreover, although pediatric patients with hematological/oncological disease are more susceptible to ATRs, the relationship between allergic predisposition and ATRs remains to be fully clarified. STUDY DESIGN AND METHODS: Patients who were diagnosed with pediatric hematological/oncological disease and received transfusion at the study institutions were included. We determined patient background information related to their allergy history, measured the levels of allergen-specific immunoglobulin E (IgE) using sera obtained on diagnosis, and analyzed their associations with ATR onset. RESULTS: Of the 363 patients analyzed, 144 developed ATRs. Multivariate analysis identified cases with high basophils in the peripheral blood, and Dermatophagoides pteronyssinus- and egg white-specific IgEs were involved in the development of ATR in all age groups. Meanwhile, a history of food allergies, and positivity for Japanese cypress- and D. pteronyssinus-specific IgEs were risk factors for developing ATRs in the <5 years age group. Moreover, patients aged 5-<10 years with a history of asthma, allergic rhinitis, pollinosis, or atopic dermatitis, and those aged ≥10 years with positivity for dog dander-specific IgE were at risk for developing ATRs. CONCLUSION: The allergic constitution of patients plays a role in ATR onset even in pediatric hematological/oncological diseases. Therefore, advance confirmation of a patient's allergic constitution may partly predict the onset of ATRs. However, since multiple allergic predispositions within complex mechanisms may be involved in the onset of ATRs, further verification is required.

How is transfusion-associated graft-versus-host disease similar to, yet different from, organ transplantation-associated graft-versus-host disease?

Graft-versus-host disease (GVHD) is a rare, usually fatal complication following blood transfusion or organ transplantation, namely transfusion-associated GVHD (TA-GVHD) and organ transplantation-associated GVHD (OA-GVHD). The dominant mechanism of GVHD is exposure to viable donor lymphocytes that are not recognized as foreign by, but able to respond to, the recipient. The clinical features and relative risk factors of either TA-GVHD or OA-GVHD are yet to be fully understood. The current review article aims to discuss and summarize the similarities and differences between TA-GVHD and OA-GVHD to gain a deeper understanding of the pathogenesis. It is evident that the shared human leukocyte antigens (HLA) between donor and recipient and immunocompromised status of the recipient are the two main risk factors for the development of both TA-GVHD and OA-GVHD. In particular, the homozygous donor with donor-dominant one-way matching at the three loci HLA-A, -B, and -DR has a high risk of developing GVHD following liver transplantation, and such donors should be excluded to prevent it. However, the development of GVHD is thought to be related to a combination of several risk factors, and the contribution of each risk factor remains unknown. Further studies are warranted to determine the important contributing factors that lead to an accurate prediction of GVHD development.

Can transfusion-associated graft-versus-host disease (TA-GvHD) be prevented with leukoreduction alone?

Transfusion-associated graft-versus-host disease (TA-GvHD) is a rare but devastating disease with a very high mortality rate. Because of the high mortality and lack of effective treatments, the current state of the art is aimed at preventing TA-GvHD and this can be accomplished via irradiation of all cellular blood products (red blood cells, granulocytes, and platelets). However, given that TA-GvHD is driven by contaminating white blood cells, and the fact that the international transfusion community has largely embraced leukoreduction, this raises the question as to whether the quantitative reduction of leukocytes via filtration can itself prevent TA-GvHD, thus allowing hospitals to skip irradiation steps? In this paper, we review the medical literature to determine how many leukocytes are needed to be removed to prevent TA-GvHD, while providing brief overviews of this entity itself and current irradiation strategies.

Reported transfusion-related acute lung injury associated with solvent/detergent plasma - A case series.

BACKGROUND: Antibody-mediated transfusion-related acute lung injury (TRALI) is caused by donor HLA or HNA antibodies in plasma-containing products. In the Netherlands 55,000 units of solvent/detergent plasma (SDP), a pooled plasma product, are transfused yearly. It's produced by combining plasma from hundreds of donors, diluting harmful antibodies. Due to a lack of reported cases following implementation, some have labeled SDP as "TRALI safe". STUDY DESIGN AND METHODS: Pulmonary transfusion reactions involving SDP reported to the Dutch national hemovigilance network in 2016-2019 were reviewed. Reporting hospitals were contacted for additional information, cases with TRALI and imputability definite, probable, or possible were included and informed consent was sought. RESULTS: A total of three TRALI and nine TACO cases were reported involving SDP. The imputability of one TRALI case was revised from possible to unlikely and excluded; in one case no informed consent was obtained. We present a case description of TRALI following SDP transfusion in a 69-year-old male, 3 days following endovascular aortic aneurysm repair. The patient received one unit of SDP to correct a heparin-induced coagulopathy, prior to removal of a spinal catheter post-operatively. Within five hours he developed hypoxemic respiratory failure requiring intubation, hypotension, bilateral chest infiltrates, and leucopenia. The patient made a full recovery. CONCLUSION: This case of TRALI, following transfusion of a single unit of SDP to a patient without ARDS risk factors, demonstrates that TRALI can occur with this product. Clinicians should remain vigilant and continue to report suspected cases, to help further understanding of SDP-associated TRALI.

Transfusion double whammy? Adrenaline-takotsubo-anaphylaxis-Kounis complex post transfusion?

BACKGROUND AND OBJECTIVES: The adrenaline-takotsubo-anaphylaxis-Kounis, or the ATAK complex, where there are clinical and pathophysiological overlaps between takotsubo and Kounis syndromes, in which histaminergic, adrenergic and other mediators may play roles, was recently described. The objective of this report was to describe three cases where the ATAK complex was suspected to have occurred after transfusion. MATERIALS AND METHODS: Three cases were recently reported to the New Zealand Blood Service haemovigilance programme that appeared to have features in common suggestive of the ATAK complex. RESULTS: All three patients had had a blood component transfused, an initial severe allergic reaction, treatment with adrenaline or a congener, subsequent acute left ventricular failure or transfusion-associated circulatory overload, and features suggestive of takotsubo cardiomyopathy. CONCLUSIONS: Although rarely described, transfusion-associated ATAK complex may be occurring more often than believed. Circumstances during a transfusion may predispose to it. It should be suspected if the sequence of events described above occur. Its characteristics need to be better understood. Risk factors for it may be modifiable.

Viscoelastic Testing Prior to Non-surgical Procedures Reduces Blood Product Use Without Increasing Bleeding Risk in Cirrhosis.

BACKGROUND/AIMS: Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM) analyze hemostatic function in patients with coagulopathy. We sought to quantify the impact of TEG and ROTEM-guided transfusion algorithms on blood product utilization in patients with cirrhosis undergoing non-surgical procedures. METHODS: We performed a systematic review and meta-analysis on the utility of viscoelastic testing prior to non-surgical procedures to determine their impact on pre-procedural blood product use and post-procedural bleeding events. Studies comparing TEG or ROTEM-guided transfusions with standard-of-care (SOC) prior to non-surgical procedures in adult patients with cirrhosis were included. Primary outcomes were fresh frozen plasma (FFP) and platelet transfusion and secondary outcomes of post-procedure bleeding, transfusion-related complications, and mortality; and were reported as standardized mean differences (SMD) and risk ratios (RR). RESULTS: Six studies (five randomized controlled trials and one cohort study) involving 367 patients met inclusion criteria. Compared with SOC, TEG/ROTEM-guided transfusions led to an overall decreased number of patients who received FFP transfusions (SMD = -0.93, 95% CI [-1.54, -0.33], p < 0.001) and platelets transfusions (SMD = -1.50, CI [-1.85, -1.15], p < 0.001). Total amount of FFP (SMD-0.86, p < 0.001) and platelet (SMD = -0.99, p < 0.001) transfused in the TEG/ROTEM group were also lower. Decreased pre-procedure transfusion in the TEG/ROTEM group did not result in increased post-procedure bleeding (RR = 0.61, p = 0.09) or in mortality (RR = 0.91, p = 0.93). CONCLUSION: In patients with cirrhosis, TEG or ROTEM significantly reduces blood product utilization prior to non-surgical procedures, with no increase in post-procedure bleeding or mortality. TEG and ROTEM utilization can promote high-value care and improve transfusion stewardship in this population.

Transfusion-related Acute Lung Injury: 36 Years of Progress (1985-2021).

The term transfusion-related acute lung injury (TRALI) was coined in 1985 to describe acute respiratory distress syndrome (ARDS) after transfusion, when another ARDS risk factor was absent; TRALI cases were mostly associated with donor leukocyte antibody. In 2001, plasma from multiparous donors was implicated in TRALI in a randomized controlled trial in Sweden. In 2003 and in many years thereafter, the U.S. Food and Drug Administration reported that TRALI was the leading cause of death from transfusion in the United States. In 2003, the United Kingdom was the first among many countries to successfully reduce TRALI using male-predominant plasma. These successes are to be celebrated. Nevertheless, questions remain about the mechanisms of non-antibody TRALI, the role of blood products in the development of ARDS in patients receiving massive transfusion, the causes of unusual TRALI cases, and how to reduce inaccurate diagnoses of TRALI in clinical practice. Regarding the latter, a study in 2013-2015 at 169 U.S. hospitals found that many TRALI diagnoses did not meet clinical definitions. In 2019, a consensus panel established a more precise terminology for clinical diagnosis: TRALI type I and TRALI type II are cases where transfusion is the likely cause, and ARDS are cases where transfusion is not the likely cause. For accurate diagnosis using these clinical definitions, critical care or pulmonary expertise is needed to distinguish between permeability versus hydrostatic pulmonary edema, to determine whether an ARDS risk factor is present, and, if so, to determine whether respiratory function was stable within the 12 hours before transfusion.