Transfusion-associated Dyspnoea Research Articles

Retrospective evaluation of indications, transfusion protocols, and acute transfusion reactions associated with the administration of lyophilized canine albumin: 53 cases (2009-2020).

To describe the administration of lyophilized canine albumin (LCA) and determine the increase in serum albumin concentrations post-LCA transfusion. To describe the incidence and types of acute transfusion reactions (TRs) and associated outcome in dogs presenting to a veterinary teaching hospital. Retrospective and descriptive study from 2009 to 2020. University teaching hospital. Fifty-three client-owned dogs included in the study if they received an LCA transfusion and had vital sign monitoring recorded for at least for 4hours after starting the LCA transfusion. None. The 53 dogs available for study inclusion received 64 LCA transfusions. Signalment; underlying disease; indications for LCA transfusion; pre- and posttransfusion serum albumin concentration; volume, concentration, and dose of LCA; duration of transfusion; administration of other blood products or synthetic colloids; occurrence, timing, and type of TR; length of hospitalization; and outcome were recorded. Serum albumin concentrations increased post-LCA transfusion, with a median dose of 0.56g/kg and a median posttransfusion serum albumin increase of 3g/L (0.3g/dL) (P=0.008). TRs occurred in 13 of 64 (20.3%) transfusion events. Volume per kilogram, dose (g/kg), concentration, duration of transfusion, and additional administration of synthetic colloids were not associated with TRs. Three (23%) TRs were classified as febrile nonhemolytic transfusion reaction, 5 (38.5%) as transfusion-associated dyspnea (development of respiratory distress and limited diagnostics), and 5 (38.5%) had clinical signs that could not be defined by any 1 TR category. Six (46.1%) of 13 events were nonsevere, 5 (38.5%) were severe, and 2 (15.4%) were life-threatening. Administration of LCA can be used to increase serum albumin concentrations, although the clinical implications of this increase are unknown. Acute TRs associated with LCA are relatively frequent and can be life-threatening. Careful monitoring is vital.

Spectrum of Hemolytic Transfusion Reactions from Tertiary Cancer Center Over a 1-year Period

Background and Objectives: Acute hemolytic transfusion reactions (HTRs) one of the serious adverse events manifesting within 24 h of blood transfusion. To review the adverse transfusion reactions in our cancer center over a 1-year period, especially HTR and its causation to find the ways of mitigating the same. Methods: This was a retrospective analysis of HTR in tertiary care cancer center from South India. Patients who developed HTR in 2022 were included for discussion. Results: A total of six HTRs observed in five patients during 1 year. Case 1 was an acute presentation of HTR due to Anti Jka antibody. Case 2 was a nonimmune HTR associated with leukodepleted irradiated packed red blood cells transfusion. Case 3 was an incidental finding of passive hemolysis due to ABO incompatible platelet transfusion in patient clinically manifesting febrile and transfusion-associated dyspnea. Case 4 presented as an HTR with inconclusive evidence suggestive of HTR, with an impression of hemolysis as a part of the underlying disease. Conclusion: While the incidence of HTR due to ABO-incompatible transfusion reactions has been minimized, the other potential causes for acute HTR are still a concern. An effective hemovigiliance and strict adherence to standards in blood component practice may help to mitigate any form of transfusion reaction.

Guideline on the investigation and management of acute transfusion reactions.

Guideline on the investigation and management of acute transfusion reactions.

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

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. 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. 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. 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.

The transfusion-associated dyspnea prospective observation and laboratory assessment study: a protocol for investigating and disambiguating cardiopulmonary and high-grade febrile transfusion reactions in adults

Background: Cardiorespiratory transfusion reactions drive most transfusion-related morbidity and mortality. Transfusion-associated circulatory overload and transfusion-related acute lung injury have established causes, important impacts, mitigation options, and revised definitions, while non-conforming CRTRs fall into a category known as transfusion-associated dyspnea. Though procedures to investigate high-risk febrile transfusion reactions are typically rooted in detecting incompatibility or bacterial contamination, a common standard for examining CRTRs is lacking. CRTRs are further challenged by charting limitations, confounding (or enhanced susceptibility) by comorbidities, and/or overlapping insults. Deeper profiling of CRTRs could improve categorizations, reveal best-value diagnostics, and decipher the nature of (and/or minimize) reactions coded as TAD. Methods: The primary objective of this multi-center study is to reduce uncertainty in final conclusions drawn on CRTRs (cases), defined by dyspnea with objective disturbances and/or significant hemodynamic insults, with/without fever (±F). HRFTRs (controls) represent higher-grade F (T≥39°C or chills/rigors or lower-grade F (≥38°C by +Δ1°C) with non-respiratory effects). Patients (goal: 200) consent to additional sampling (≤24h post-TR) to identify contributing factors in case/control presentations, and in diagnostic groups (TRALI, TACO±F, TAD). Mechanistic axes of interest are cardiorenal, hemolytic, leukoagglutinating, biolipid, vasoactive, and inflammatory. Secondary goals include elucidation of real-life “insult-multiplicity” in CRTRs, tests of greatest yield, and distinguishing features in TRALI/TACO/TAD. Conclusions: A deep systematic CRTR probe may not only reduce diagnostic uncertainty but frame biomarker performance and pathologic signatures in definition-specific CRTRs. The re-classifiability or biology of TAD may be better understood. High-quality, mechanistic, true-to-quantity hemovigilance better exposes burdens and management options. Trial Registration: The trial is registered with ClinicalTrials.gov. with registry number NCT04267029.

Receiver Operating Characteristics of NT-Probnp in the Transfusion Associated Dyspnea: Prospective Observation & Laboratory Assessment (TADPOL) Study of Cardiorespiratory Versus Febrile Presentation Archetypes

BACKGROUND: B-type natriuretic peptide (BNP) is a hormone secreted in response to volume-related ventricular stretch, and as a biomarker is both diagnostic and prognostic in heart failure. Elevation in BNP or its equimolar N-terminal prohormone fragment (NT-proBNP, noteworthy for its longer half-life) qualifies as a criterion in ISBT-IHN-AABB guidelines for the diagnosis of transfusion-associated circulatory overload (TACO). However, real-life range comparisons in TACO vs. non-respiratory transfusion reactions (TR) are lacking. In the Transfusion Associated Dyspnea-Prospective Observation and Laboratory Assessment (TADPOL) study of acute TRs requiring laboratory investigation (cardiorespiratory events +/- fever [CRTR+/-F] vs. standalone high-risk fevers [HRFTR]), patients consented to NT-proBNP testing as part of a multi-dimensional assessment of presentation archetypes and final diagnoses (e.g., TACO, transfusion-associated dyspnea [TAD], febrile non-hemolytic TR [FNHTR]). METHODS: Blood samples were collected within 24h of reaction onset from patients enrolled across 6 centers in the study's first 134 weeks. NT-proBNP (ng/L) was quantified by chemiluminescence immunoassay (Roche Diagnostics) in real-time (3 sites) or by batched testing (3 sites); reference cut-off values to rule in a cardiac cause for dyspnea in the acute care setting were >450 (age <50y), >900 (age 50-75y), and >1800 (age >75y). Summary statistics are reported. Relationships to provisional reaction diagnosis and clinical features were also explored using appropriate tests (Student's t-test, Mann-Whitney U, Pearson's correlation, and/or Fisher's exact test). Discrimination between possible-to-definite TACO and doubtful or ruled-out TACO was assessed using receiver operating characteristic (ROC) curve analysis with logistic regression. RESULTS: At the study mid-point, 1180 TR (604 TADPOL-eligible) occurred, with NT-proBNP tested in 77/100 enrolled patients. NT-proBNP was significantly higher in patients enrolled in the CRTR arms compared to HRFTR (p=0.0009), with no difference between CRTR+F and CRTR-F (p=0.4). NT-proBNP was also significantly higher in patients with dyspnea in the TR (p=0.005). There was no correlation between NT-proBNP and systolic blood pressure change (p=0.1) or at baseline (p=0.1). Provisional reaction diagnoses were available for 55 patients including 32/39 in the CRTR arms: for possible-to-definite TACO (n=14) and TAD (n=19), vs. standalone FNHTR (n=38), the median NT-proBNP (IQR) was 3,439 (1,587-10,668) and 1,893 (674-5,361), vs. 710 (124-10,542), respectively. Transfusion-related acute lung injury was considered possible in 3 cases, all with TACO. Among CRTR, there was a trend towards higher NT-proBNP values in patients with TACO (p=0.05), with no difference in ages (p=0.8). Using the age-adjusted reference cut-off, the sensitivity of high NT-proBNP for TACO was 86%; specificity was 54% when differentiating TACO from all enrolled TR and 38% between TACO and non-TACO CRTR. In ROC curve analysis (Fig. 1), the area under the curve was 72% (95% CI 55-88%) and the threshold value for discriminating TACO from other TR was 1606 with 60% sensitivity and 65% specificity (Fig. 2). CONCLUSIONS: NT-proBNP is strongly correlated with dyspneic TRs compared to isolated febrile TRs. Elevations appeared more marked in TACO, with a sensitivity of 86% using existing laboratory reference values. However, specificity and discrimination within CRTR were poor. These results affirm that NT-proBNP is helpful in ruling out TACO, whereas ruling in TACO continues to demand a more integrated approach. Whether cardiac strain in unclassified CRTR and TAD is evidence of missed TACO or other insults remains to be determined. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Adverse reactions following transfusion of blood components, with a focus on some rare reactions: Reports to the International Haemovigilance Network Database (ISTARE) in 2012-2016.

The International Haemovigilance Network's (IHN) ISTARE database collects surveillance data on all adverse reactions (AR) associated with transfusion of blood and blood components, facilitating the sharing of best practice and benchmarking for improving blood safety and quality. Up to 2012, no publications discussed certain rare AR. The aim of this study is to examine ISTARE data on AR from 2012 to 2016, focusing on hypotensive reactions, post-transfusion purpura (PTP), transfusion-associated graft versus host disease (TA-GvHD), hyperkalemia and hypocalcemia. National Haemovigilance Systems (HVS), provided aggregate annual data on AR by type of reaction, severity, imputability to transfusion, and blood component implicated. Twenty-nine HVS provided 104 annual reports covering 107,778,290 blood units issued. Among AR reported, 25% were serious, including 368 deaths. The 284 transfusion-transmitted infections included 187 bacterial infections, 84 viral and 13 parasitic or fungal; nine deaths resulted. AR related to the respiratory system transfusion-associated circulatory overload, transfusion-related acute lung injury and transfusion-associated dyspnoea accounted for 8.3% of all AR, 20.1% of serious, and 52.2% of deaths. Of 1634 rare AR, 1565 were hypotensive, 38 PTP, 17 GvHD, 9 hyperkalemia and 5 hypercalcemia. Half were serious and 16 fatalities were recorded (13 hypotensive, 2 GvHD, one PTP). Among 14 countries that reported any hypotensive AR, incidences diverged widely. ARs in this group are frequently severe or life-threatening. Hypotensive AR are the most common, but may have been overlooked and counted under allergic and other AR presenting with hypotension. Compliance with the ISBT definition may be suboptimal, thus its real incidence may be higher. Data on GvHD may contribute to clarifying the role of leukodepletion with or without irradiation. ISTARE continues to be a useful surveillance tool for all transfusion AR and provides relevant insights into overlooked and rare AR, thus offering important contributions towards maximising transfusion safety.

Plasma, platelets and cryoprecipitates therapies

The present review gives an overview of the components, applications and risks of transfusion therapy. Fresh frozen plasma (FFP) transfusion is a widely used procedure both in a prophylactic and therapeutic context. In both scenarios the method of administration and the dosage are, improperly, the same; it is reported that in the clinical context FFP is inappropriately used in over 50% of cases. According to different guidelines its only recommended use is in a condition of critical hemorrhage, as there is no evidence of positive outcomes in its prophylactic administration. Platelet concentrates (PCs) are broadly used to support patients with thrombocytopenia, whether it is pre or postoperative, or in intensive care medicine. The only consensus on its use is the prophylactic administration when the patient’s platelet count is lower than 10,000. Another use of PCs can be in reducing side effects and enhancing the effects of specific drugs, although this application is still complex. Cryoprecipitate usage in clinics is decreasing both due to its variable content of factors I, VIII, XIII and von Willebrand, and the amount of time necessary to obtain it. Of great importance in the transfusion therapy framework are the respiratory complications that can occur, such as Transfusion-Associated Cardiac Overload (TACO), Transfusion-Related Acute Lung Injury (TRALI), Transfusion-Associated Dyspnea (TAD) and transfusion-induced sepsis. The suggested procedure when any of these (and other) complications occur is to seek consultation from the transfusion medicine unit.

Development of the Chinese Haemovigilance Network and reporting of adverse transfusion reactions from 2018 to 2020.

To advance blood transfusion safety, the Chinese Haemovigilance Network (CHN) was put into operation in 2018. This report describes the development of the CHN and evaluates its role by analysing reported adverse transfusion reactions (ATRs) from 2018 to 2020. All data in this study were obtained from the CHN online reporting platform. A timeline of CHN development is presented, and the activities of CHN-enrolled facilities are analysed by year. The reported ATRs were analysed in detail for ATR types, blood components involved and adherence to case definition, severity and imputability criteria. Incidence rates were calculated and compared with international examples. During 2018-2020, a total of 3061 ATRs were reported through the CHN online reporting system. The rate of reported ATRs in all facilities and the 10 highest reporting facilities was 0.7‰ and 1.8‰, respectively. When analysed by year, the incidence rate showed an increasing trend from 2018 to 2020. Allergic (68.2%) and febrile non-haemolytic transfusion reaction (27.1%) were the most common. The vast majority of ATRs (92.0%) were not serious, but serious cases of transfusion-associated circulatory overload, transfusion-associated dyspnoea and hypotensive reaction were common. Most (86.0%) of reported cases were definitely or probably associated with transfusion. Under-reporting of ATRs occurs in many Chinese hospitals, but the establishment of CHN has increased ATR recognition and management. More effort will be needed in the future to detect transfusion problems and improve transfusion practice in China.

Transfusion-related respiratory complications in intensive care: A diagnosis challenge.

Transfusion-related respiratory complications can be challenging to diagnose especially in mechanically-ventilated patients in the intensive care unit (ICU) due to the concurrent respiratory symptoms associated with the patients' primary diagnoses. In this narrative review, transfusion-related respiratory complications, including transfusion-associated dyspnea (TAD), transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and transfusion-related allergic reaction (TRAR), are briefly presented in light of the recent consensus or experts' definitions; and the diagnosis issues for ICU patients are discussed. Acute respiratory failure occurring during, or within 6 to 24hours, of transfusion might be a transfusion-related respiratory complication. The recent updated definitions for TRALI and TACO should assist clinicians to differentiate between possible diagnoses. The issues for ICU clinicians are first to recognize the acute respiratory deterioration and the possible causality between the deterioration and blood transfusion and secondly to make the proper diagnosis. This remains challenging for mechanically-ventilated patients. Clinical assessment to identify ICU patients at particular risk of transfusion-related respiratory complications and non-invasive investigation tools could be beneficial and may help to remind clinicians to be alert to the link between transfusion and worsening of respiratory symptoms in these vulnerable critically ill patients.

Transfusion-related adverse reactions: Data from the National Healthcare Safety Network Hemovigilance Module - United States, 2013-2018.

Despite current blood safety measures, transfusion recipients can experience transfusion-related adverse reactions. Monitoring these reactions can aid in understanding the effectiveness of current transfusion safety measures. Data from the National Healthcare Safety Network Hemovigilance Module were used to quantify adverse reaction risk. Facilities reporting at least one month of transfused blood components and transfusion-related adverse reactions during January 2013-December 2018 were included. Adverse reaction rates (number per 100,000 components transfused) were calculated for transfused components stratified by component type, collection, and modification methods. During 2013-2018, 201 facilities reported 18,308 transfusion-related adverse reactions among 8.34 million blood components transfused (220/100,000). Adverse reactions were higher among apheresis (486/100,000) and pathogen-reduced platelets (579/100,000) than apheresis red blood cells (197/100,000). Allergic reactions (41%) were most common. There were 23 fatalities and 9% of all adverse reactions were serious (severe, life-threatening, or fatal). Reactions involving pulmonary complications (transfusion-associated circulatory overload, transfusion-related acute lung injury and transfusion-associated dyspnea) accounted for 35% of serious reactions but 65% of fatalities. Most (76%) of the 37 transfusion-transmitted infections were serious; none involved pathogen-reduced components. One in 455 blood components transfused was associated with an adverse reaction although the risk of serious reactions (1 in 6224) or transfusion-transmitted infections (1 in 225,440) was lower. Some serious reactions identified were preventable, suggesting additional safety measures may be beneficial. Higher reaction rates identified among pathogen-reduced platelets require further study. These findings highlight the importance of monitoring reactions through national hemovigilance to inform current safety measures and the need for strategies to increase healthcare facility participation.

Frequency and timing of all‐cause deaths in visits involving suspected transfusion reactions, and the significance of cardiopulmonary disturbances

Transfusion reactions (TRs) may cause or contribute to death. Cardiopulmonary TRs are distressing, and collectively account for most transfusion fatalities, though the degree to which they alter survival more broadly is unclear. Deaths (and their timing) after TRs may provide further insights. Adult (tri-hospital network) haemovigilance data (2013-2016) recorded referrals with conclusions ranging from unrelated to transfusion (UTR) to entities such as: septic TRs, serologic/haemolytic reactions, transfusion-associated circulatory overload (TACO), transfusion-associated dyspnoea (TAD), transfusion-related acute lung injury (TRALI), allergic transfusion reaction (ATR), and others. For (in- or out-patient) visits involving suspected TRs (VISTRs), all-cause mortalities (% [95% confidence interval]) and associated time-to-death (TTD) (median days, [interquartile range]) were compared. Diagnoses were defined inclusively (possible-to-definite) or strictly (probable-to-definite). Of 1144 events, rank order VISTR mortality following (possible-to-definite) TRs, and associated TTDs, were led by: DHTR 33% [6-19], 1 death at 123d; TRALI 32% [15-54], 6 deaths: 3d [2-20]; BaCon 21% [14-31], 17 deaths: 10d [3-28]; TACO 18% [12-26], 23 deaths: 16d [6-28]; TAD 17% [11-26]: 18 deaths, 6d [3-12]. Higher-certainty TRs ranked similarly (DHTR 50% [9-91]; BaCon 29% [12-55], 4 deaths: 12d [3-22]; and TACO 25% [16-38], 15 deaths: 21d [6-28]). VISTR mortality after TACO or TRALI significantly exceeded ATR (3·3% [2·4-5·8], P<0·00001) but was not different from UTR events (P=0·3). Only half of cardiopulmonary TRs constituted high certainty diagnoses. Nevertheless, cardiopulmonary TRs and suspected BaCon marked higher VISTR mortality with shorter TTDs. Short (<1week) TTDs in TAD, BaCon or TRALI imply either contributing roles in death, treatment refractoriness and/or applicable TR susceptibilities in the dying.

A Study of Frequency and Pattern of Adverse Transfusion Reactions at a Blood Bank in a Tertiary Care Hospital: Towards Hemovigilance

Background: Adequate and safe transfusion facility of blood and its components is necessary as blood transfusions are a part of life saving measures in medical and surgical emergencies. However, transfusion practice could result in non-fatal to fatal adverse transfusion reactions (ATR). Therefore, it is important to identify various adverse reactions so that steps can be taken to minimize such reactions and ensure safer transfusion being carried out.&#x0D; Methods: All ATRs reported to the blood bank from January 2013 to December 2016 were reviewed and analysed. The frequency of ATRs and its association with various component types were assessed.&#x0D; Result: During the study period, a total of 199106 units of blood were issued from the blood bank out of which there was an incidence of 77 (0.12%) transfusion reactions. Chills/rigors was the most common symptom (27.3%) of the symptomatic cases followed by pruritis (23.4%)&#x0D; Majority of the transfusion reaction were non haemolytic, 76 (98.7%) cases. One case was of haemolytic transfusion reaction. Among the non-haemolytic transfusion reactions, febrile non haemolytic transfusion reaction (FNHTR) constituted 28 (36.4%) and allergic reactions constituted 41(53.2%). Other transfusion reactions including hypotensive transfusion reaction (HTR), 1 (1.3%) case and transfusion associated dyspnoea (TAD), 6 (7.8%) cases were also seen. The frequency of ATRs was highest with packed red cells (PC) being 75.3% and least with platelet concentrate (PLTC) being 11.7%.&#x0D; Conclusion: The frequency of ATRs in our blood bank was found to be on a lower scale when compared to that of most of the similar studies. Allergic reactions and FNHTR were the most common ATRs seen, introduction of leukoreduction filters would help reduce FNHTRs.

Respiracijske transfuzijske reakcije

Respiratory transfusion-related reactions are not very frequent, partly also because recognition and reporting transfusion reactions is still underemphasized. Tis article describes the most important respiratory transfusion reactions, their pathophysiology, clinical picture and treatment strategies. Respiratory transfusion related reactions can be primary or secondary. The most important primary transfusion-related reactions are TRALI - transfusion-related acute lung injury, TACO – transfusion-associated circulatory overload, and TAD - transfusion-associated dyspnea. TRALI is immuneassociated injury of alveolar basal membrane, which becomes highly permeable and causes noncardiogenic pulmonary edema. Treatment of TRALI is mainly supportive with oxygen, fluids (in case of hypotension) and in cases of severe acute respiratory failure also mechanic ventilation. TACO is caused by volume overload in predisposed individuals, such as patients with heart failure, the elderly, infants, patients with anemia and patients with positive fluid balance. Clinical picture is that of a typical pulmonary cardiogenic edema, and the therapy is classical: oxygen and diuretics, and in severe cases also non-invasive or invasive mechanical ventilation. TAD is usually a mild reaction of unknown cause and cannot be classified as TACO or TRALI, nor can it be ascribed to patient’s preexisting diseases. Although the transfusion-related reactions are not very common, knowledge about them can prevent serious consequences. On the one hand preventive measures should be sought, and on the other early recognition is beneficial, so that proper treatment can take place.

Transfusion-associated hypoxemia in pediatric patients with solid tumors after autologous peripheral blood stem cell transplantation

BackgroundAlthough several types of transfusion-related adverse reactions (TRARs) have been reported, one of the most important involves respiratory features during and after blood transfusion. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the most severe adverse events following blood transfusion, whereas transfusion-associated dyspnea (TAD) is a less severe respiratory distress. However, there exists little evidence of these factors in pediatric populations. Case reportHere, two cases of atypical TRARs with respiratory features, in pediatric patients with solid tumors, appearing after transfusion of platelet concentrate following autologous peripheral blood stem cell transplantation are reported. Both patients developed mild hypoxemia during PC transfusion, which continued for approximately 2 weeks. Chest radiography in either patient did not reveal any abnormalities that are included in the criteria of either TRALI or TACO. Both patients recovered following oxygen administration. ConclusionThis complication of TRARs with respiratory features may occur more frequently in pediatric populations than realized because it may be under-recognized or under-reported. Accumulation of additional cases, including non-typical cases, is necessary to fully understand the pathology of TRARs, correctly classify these reactions, and improve care of patients receiving blood transfusions.

Inpatient Non-Hemolytic Delayed Serologic Transfusion Reactions and Hospital Length of Stay: Is There an Association?

Introduction Anti-erythroid antibodies are the classical marks of serologic and hemolytic transfusion reactions. These reactions can occur acutely or in a delayed timeframe, while the sensitizing antibody may derive from the host or be passively acquired. In those with concurrent hemolysis, the red blood cell (RBC) breakdown may be severe enough to command supportive care. However, in those with non-hemolytic delayed serologic transfusion reactions (NH-DSTRs), the threat applies more towards the future rather than the present time. Downstream hazards range from hemolytic disease of the newborn, to delays and difficulties sourcing antigen-negative blood (when the antibody is known), or an anamnestic response with higher odds of hemolysis on antigen re-exposure (when the antibody becomes unknown by evanescence and healthcare fragmentation). Data are lacking on inpatient outcomes associated with discovering a new NH-DSTR during a hospital admission. A review of NH-DSTRs was thus performed in a large academic hospital (34,000 RBC dispensations annually). Methods A retrospective review of a transfusion reaction database was undertaken at a large academic hospital in Toronto, Canada. Transfusion reactions (TRs) occurring during inpatient admissions (excluding emergency room and outpatient visits) from 1/1/2010-31/12/2015 were included. NH-DSTR was defined as the presence of a new antibody on repeat screen post transfusion with no evidence of hemolysis. Other anti-RBC antibody mediated TRs included acute hemolytic transfusion reactions (AHTR) (both host-derived and passively-acquired [from products such as intravenous immunoglobulin]), and delayed hemolytic transfusion reactions (DHTR) occurring with or without serologic findings. A comparison was also made against all inpatient TRs not due to RBC antibodies (non-anti-RBC TRs). Disturbances deemed unrelated to transfusion were excluded. Outcomes included length of stay (LOS), interval between TR recognition and discharge, severity of TR (as per the International Society of Blood Transfusion grading system), and death. Results A total of 783 inpatient TRs were reviewed. The distribution of TRs (Figure 1) included 562 (71.8%) non-anti-RBC TRs and 221 (28.2%) anti-RBC TRs. Within the anti-RBC TRs, 159 (71.9%) were classified as NH-DSTRs. The mean age of all patients was 57 (± 17) with 49.4% of reactions occurring in females. Compared with non-anti-RBC and other anti-RBC transfusion reactions, NH-DSTRs were significantly less frequently classified as severe (Table 1). The overall LOS and remaining days in hospital after TR were significantly longer in those with NH-DSTRs compared with the two other groups (Table 1). Post-reaction LOS was longer by a median of 5 or 7 days for NH-DSTR versus non-anti-RBC TRs and other anti-RBC TRs respectively. There was no significant difference between groups when evaluating inpatient mortality. Conclusions NH-DSTRs are associated with a longer LOS when compared with all other TRs. This relationship holds even in comparisons with other anti-RBC TRs. Causality is not established by this analysis, nor is there a biologic rationale for a NH-DSTR to directly impact LOS. However, the propensity to form a new anti-RBC antibody may reflect an underlying pro-inflammatory comorbid state that itself may be influencing LOS. Further studies are needed to confirm this association. Nevertheless, given any potential for additional/current impacts beyond future ramifications, the precautionary principle is strengthened for the value of curating the full extent of a recipient's antibody history, and prophylactically matching for minor antigens if resources permit. Table 1 Comparison of outcomes between NH-DSTRs versus non-anti-RBC TRs and other-anti-RBC TRs. Table 1. Comparison of outcomes between NH-DSTRs versus non-anti-RBC TRs and other-anti-RBC TRs. Figure 1 Frequency of transfusion reactions from January 1, 2010 to December 31, 2015. Abbreviations: allergic transfusion reaction (ATR), febrile non-hemolytic transfusion reaction (FNHTR), transfusion associated circulatory overload (TACO), transfusion associated dyspnea (TAD), bacterial contamination (BaCon), transfusion related acute lung injury (TRALI), inflammatory transfusion reaction (ITR), citrate reaction (CR), acute passive serologic/hemolytic transfusion reaction (APSHTR). Figure 1. Frequency of transfusion reactions from January 1, 2010 to December 31, 2015. Abbreviations: allergic transfusion reaction (ATR), febrile non-hemolytic transfusion reaction (FNHTR), transfusion associated circulatory overload (TACO), transfusion associated dyspnea (TAD), bacterial contamination (BaCon), transfusion related acute lung injury (TRALI), inflammatory transfusion reaction (ITR), citrate reaction (CR), acute passive serologic/hemolytic transfusion reaction (APSHTR). Disclosures No relevant conflicts of interest to declare.

The International Haemovigilance Network Database for the Surveillance of Adverse Reactions and Events in Donors and Recipients of Blood Components: technical issues and results.

The International Haemovigilance Network's ISTARE is an online database for surveillance of all adverse reactions (ARs) and adverse events (AEs) associated with donation of blood and transfusion of blood components, irrespective of severity or the harm caused. ISTARE aims to unify the collection and sharing of information with a view to harmonizing best practices for haemovigilance systems around the world. Adverse reactionss and adverse events are recorded by blood component, type of reaction, severity and imputability to transfusion, using internationally agreed standard definitions. From 2006 to 2012, 125 national sets of annual aggregated data were received from 25 countries, covering 132.8 million blood components issued. The incidence of all ARs was 77.5 per 100 000 components issued, of which 25% were severe (19.1 per 100 000). Of 349 deaths (0.26 per 100 000), 58% were due to the three ARs related to the respiratory system: transfusion-associated circulatory overload (TACO, 27%), transfusion-associated acute lung injury (TRALI, 19%) and transfusion-associated dyspnoea (TAD, 12%). Cumulatively, 594 477 donor complications were reported (rate 660 per 100 000), of which 2.9% were severe. ISTARE is a well-established surveillance tool offering important contributions to international efforts to maximize transfusion safety.

Transfusion-associated dyspnea--shadow or substance?

New Zealand Blood Service Haemovigilance uses International Society of Blood Transfusion/International Haemovigilance Network definitions to categorize transfusion reactions (TR). Transfusion-associated dyspnoea (TAD) is a category for TR with respiratory features (TRRF) that do not fit definitive entities. TRRF, including TAD, are clinically significant. TR classified as TAD were reviewed. We found that many TAD may have been transfusion-associated circulatory overload. Better information in TR reports and refining TR diagnostic criteria may result in less misclassification of TRRF. TAD may represent mild, atypical or overlap entities, and there may be a residuum of cases with currently unexplained pathophysiology.

Analysis of leucocyte antibodies, cytokines, lysophospholipids and cell microparticles in blood components implicated in post‐transfusion reactions with dyspnoea

Post-transfusion reactions with dyspnoea (PTR) are major causes of morbidity and death after blood transfusion. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are most dangerous, while transfusion-associated dyspnoea (TAD) is a milder respiratory distress. We investigated blood components for immune and non-immune factors implicated in PTR. We analysed 464 blood components (RBCs, PLTs, L-PLTs, FFP) transfused to 271 patients with PTR. Blood components were evaluated for 1/antileucocyte antibodies, 2/cytokines: IL-1β, IL-6, IL-8, TNF-α, sCD40L, 3/lysophosphatidylcholines (LysoPCs), 4/microparticles (MPs) shed from plateletes (PMPs), erythrocytes (EMPs) and leucocytes (LMPs). Anti-HLA class I/II antibodies or granulocyte-reactive anti-HLA antibodies were detected in 18.2% of blood components (RBC and FFP) transfused to TRALI and in 0.5% of FFP transfused to TAD cases. Cytokines and LysoPCs concentrations in blood components transfused to PTR patients did not exceed those in blood components transfused to patients with no PTR. Only EMPs percentage in RBCs transfused to patients with TRALI was significantly higher (P < 0.05) than in RBCs transfused to patients with no PTR. Immune character of PTR was confirmed mainly in 1/5 TRALI cases. Among non-immune factors, only MPs released from stored RBCs are suggested as potential mediators of TRALI. Our results require further observations in a more numerous and better defined group of patients.

Incidence of acute transfusion reactions to platelets in hospitalized pediatric patients based on the US hemovigilance reporting system

Transfusion reactions in pediatric populations have not been well studied. We investigated the incidence and type of transfusion reactions to platelets (PLTs) in a pediatric inpatient population. Over 1 year, a retrospective review of all PLT transfusions given to pediatric inpatients (≤ 18 years old) was performed at a single institution with application of the US hemovigilance reporting definitions. Intraoperative transfusions were excluded. Any signs or symptoms that could represent an acute transfusion reaction (ATR) within 24 hours after PLT transfusion were reviewed and classified based on the US hemovigilance reporting definitions. Between June 1, 2010, and May 31, 2011, a total of 805 PLT transfusions to 126 patients were identified as appropriate for inclusion. Of these 805 transfusions, 116 (14.4%) met the reporting criteria for ATRs. Some PLT transfusions were associated with multiple types of ATRs leading to 120 ATRs overall, as defined by the US hemovigilance reporting system. Of these 120 reportable ATRs, 54 (45.0%) transfusion-associated dyspnea (TAD) reactions, 38 (31.7%) febrile nonhemolytic transfusion reactions, 15 (12.5%) allergic transfusion reactions, eight (6.7%) hypotensive transfusion reactions, and five (4.2%) transfusion-associated cardiac overload reactions were identified. No resultant deaths associated with ATRs were observed. Of these reportable ATRs, only four (3.34%) were reported to the hospital transfusion service. Our findings indicate that reportable ATRs in the pediatric populations may be more prevalent than previously reported and were underreported to our transfusion service. TAD encompassed the majority of reportable ATRs and is the main contributor to the increased rate of reportable ATRs.