Acute transfusion reactions: TRALI, TACO, allergic, haemolytic, and septic

Acute haemolytic (ABO mismatch): mortality 30-40% (mostly from clerical error — prevent with barcode ID). TRALI: mortality 5-10% (lower than other ARDS); resolves in 48-72h; male-only plasma donors reduces incidence. TACO: mortality <5% (treat with diuretics); common in elderly/heart failure — prevent with slow transfusion. Anaphylactic (IgA deficiency): mortality low with prompt adrenaline; prevent with washed products. Septic (platelets): mortality 10-20% (Gram-negative worse); bacterial screening + pathogen reduction reduces. TRICC trial (1998): restrictive (Hb 70) safe; fewer transfusions = fewer reactions. TA-GVHD: mortality >90% (prevent with irradiated products for immunocompromised). Haemovigilance: reporting systems have reduced reaction rates dramatically since implementation.

TRICC (Hebert, NEJM 1999): ICU patients (n=838), Hb <70 (restrictive, transfuse at 70, target 70-90) vs <100 (liberal). 30-day mortality equivalent; restrictive group received 54% fewer transfusions and had lower in-hospital mortality in the less-ill (APACHE II <=20) and younger (<55) subgroups.[7] Landmark trial establishing restrictive transfusion in ICU. FOCUS (Carson, NEJM 2011): hip-fracture surgery in elderly (n=2016), Hb <80 (symptomatic, target ~80) vs <100. No difference in mortality or functional recovery; restrictive non-inferior. Established the 80 threshold in elderly surgical patients.[10] TRISS (Holst, NEJM 2014): septic shock ICU (n=998), Hb <70 vs <90. 90-day mortality identical (27.8% vs 27.5%); restrictive group used 50% fewer RBC units; no increase in ischaemic events. Restrictive strategy confirmed safe in septic shock.[8] PROPPR (Holcomb, JAMA 2015): severe trauma (n=680), 1:1:1 (plasma:platelet:RBC) vs 1:1:2 ratio. No difference in 24-h or 30-d mortality, but 1:1:1 achieved earlier haemostasis and fewer exsanguination deaths.[9] Foundation for modern massive haemorrhage protocols. Vlaar TRALI Consensus 2019 (Transfusion): redefined TRALI as ALI within 6 h of transfusion with no other risk factor (Type I) or with a competing risk factor deemed less contributory (Type II / possible TRALI). Standardised global case definitions for surveillance and trials.[1] Toy revised nomenclature 2017 (Transfusion): harmonised TRALI terminology between European and US groups; introduced the "possible TRALI" category.[11] Middelburg plasma meta-analysis (Transfusion 2017): male-only / male-predominant plasma donors reduce TRALI risk without compromising supply; basis for universal male-predominant plasma policies in high-income countries.[12] Roubinian TACO risk factors (Crit Care Med 2018): identified older age, heart failure, renal dysfunction, positive fluid balance, and larger transfusion volume as independent TACO predictors; supports pre-transfusion risk stratification.[13] Bux/Sachs HLA class II TRALI (Blood 2011): delineated the antibody-mediated neutrophil-activation mechanism of TRALI, particularly for HLA class II antibodies.[14] AABB RBC transfusion guideline 2023 (Carson, JAMA): Hb 7 g/dL threshold for hospitalised stable adults, 8 g/dL for those undergoing orthopaedic/cardiac surgery or with pre-existing cardiovascular disease; restricts recommendation to symptom/physiology-guided transfusion.[6]

Leucoreduction: universal pre-storage leucoreduction reduces febrile non-haemolytic reactions, CMV transmission, and contributes to TRALI reduction; standard in most high-income countries. Male-predominant plasma (TRALI mitigation): excluding previously-pregnant female donors from plasma/apheresis-platelet donation reduced TRALI incidence by ~60-70% where adopted.[12] Irradiation (TA-GVHD mitigation): 25-50 Gy gamma or X-ray irradiation of cellular products for immunocompromised recipients, neonates, and directed donations; the ONLY effective TA-GVHD prevention (leucoreduction alone is insufficient). Bacterial screening of platelets: mandatory culture or rapid detection reduces septic reactions; pathogen-reduction technology (amotosalen/UVA, riboflavin/UVB) further lowers risk and may extend shelf-life. Restrictive transfusion strategy: the single most effective reaction-prevention measure is to transfuse fewer units — TRICC, TRISS, FOCUS, and the 2023 AABB guideline all endorse a restrictive (Hb 70) strategy for most stable ICU patients.[6] Single-unit policy: transfuse one unit, reassess, only give the next if still indicated — reduces TACO and unnecessary exposure. Patient identification: two-person bedside check + barcode/PDA identification at sampling, labelling, and administration prevents ABO-mismatch acute haemolytic reactions (overwhelmingly due to clerical error).