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
DOI:
https://doi.org/10.18203/2349-3259.ijct20230051Keywords:
Transfusion, Hemovigilance, TAD, TACO, TRALI, FeverAbstract
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.
References
Roubinian N, Murphy EL. Transfusion-associated circulatory overload (TACO): prevention, management, and patient outcomes. Int J Clin Transfus Med. 2015;3:17-28.
Wiersum-Osselton JC, Whitaker B, Grey S, Land K, Perez G, Rajbhandary S, Andrzejewski C, et al. Revised international surveillance case definition of transfusion-associated circulatory overload: a classification agreement validation study. Lancet Haematol. 2019;6:e350-e8.
Hendrickson JE, Roubinian NH, Chowdhury D, Brambilla D, Murphy EL, Wu Y, et al. Incidence of transfusion reactions: a multicenter study utilizing systematic active surveillance and expert adjudication. Transfusion. 2016;56:2587-96.
Bosboom JJ, Klanderman RB, Zijp M, Hollmann MW, Veelo DP, Binnekade JM, et al. Incidence, risk factors, and outcome of transfusion-associated circulatory overload in a mixed intensive care unit population: a nested case-control study. Transfusion. 2018;58:498-506.
Sachs UJ. Recent insights into the mechanism of transfusion-related acute lung injury. Curr Opin Hematol. 2011;18:436-42.
Vlaar APJ, Toy P, Fung M, Looney MR, Juffermans NP, Bux J, et al. A consensus redefinition of transfusion-related acute lung injury. Transfusion. 2019;59:2465-76.
Domen RE, Hoeltge GA. Allergic transfusion reactions: an evaluation of 273 consecutive reactions. Arch Pathol Lab Med. 2003;127:316-20.
Badami KG. Transfusion double whammy? Adrenaline-takotsubo-anaphylaxis-Kounis complex post transfusion? Vox Sang. 2022;117:862-5.
Rollins MD, Molofsky AB, Nambiar A, Pandey S, Weiskopf RB, Toy P. Two septic transfusion reactions presenting as transfusion-related acute lung injury from a split plateletpheresis unit. Crit Care Med. 2012;40:2488-91.
Bux J, Sachs UJ. Pulmonary transfusion reactions. Transfus Med Hemother. 2008;35: 337-45.
Cohen R, Escorcia A, Tasmin F, Lima A, Lin Y, Lieberman L, et al. Feeling the burn: the significant burden of febrile nonhemolytic transfusion reactions. Transfusion. 2017;57:1674-83.
Annual SHOT Report. Available at: https://www. shotuk.org/shot-reports/. Accessed on 20 November 2021.
Fatalities reported to FDA following blood collection and transfusion annual summary for FY2016. Available at: https://www.fda.gov/media/111226/ download. Accessed on 20 November 2021.
Health Canada transfusion transmitted injuries surveillance system, 2009 – 2013 Report. Available at: https://www.canada.ca/en/public-health/services/ publications/drugs-health-products/transfusion-transmitted-injuries-surveillance-system-ttiss-2009-2013-summary-results.html. Accessed on 20 November 2021.
Politis C, Wiersum JC, Richardson C, Robillard P, Jorgensen J, Renaudier P, et al. The international haemovigilance network database for the surveillance of adverse reactions and events in donors and recipients of blood components: technical issues and results. Vox Sang. 2016;111:409-17.
McVey MJ, Cohen R, Arsenault V, Escorcia A, Tasmin F, Pendergrast J, et al. Frequency and timing of all-cause deaths in visits involving suspected transfusion reactions, and the significance of cardiopulmonary disturbances. Vox Sang. 2021;116: 898-909.
Andrzejewski C, Cloutier D, Unold D, Friedberg R. Improving patient safety in transfusion medicine: contemporary challenges and the roles for bedside and laboratory biovigilance in addressing them. Int J Clin Transfus Med. 2014;2:45-57.
Lieberman L, Maskens C, Cserti-Gazdewich C, Hansen M, Lin Y, Pendergrast J, et al. A retrospective review of patient factors, transfusion practices, and outcomes in patients with transfusion-associated circulatory overload. Transfus Med Rev. 2013;27: 206-12.
Thomas JT, Kelly RF, Thomas SJ, Stamos TD, Albasha K, Parrillo JE, Calvin JE. Utility of history, physical examination, electrocardiogram, and chest radiograph for differentiating normal from decreased systolic function in patients with heart failure. Am J Med. 2002;112:437-45.
Juffermans NP, Vlaar AP. Possible TRALI is a real entity. Transfusion. 2017;57: 2539-41.
Kojicic M, Li G, Hanson AC, Lee KM, Thakur L, Vedre J, et al. Risk factors for the development of acute lung injury in patients with infectious pneumonia. Crit Care. 2012;16:46.
Wiener-Kronish J, Nozari A. Blood transfusions and infected lungs--worse outcomes?. Crit Care Med. 2014;42:1739-40.
Parmar N, Pendergrast J, Lieberman L, Lin Y, Callum J, Cserti-Gazdewich C. The association of fever with transfusion-associated circulatory overload. Vox Sang. 2017;112:70-8.
Robillard P, Itaj NK, Chapdelaine A. Increasing incidence of transfusion-associated circulatory overload reported to the Quebec Hemovigilance System, 2000-2006. Transfusion. 2008.
Andrzejewski C, Popovsky MA, Stec TC, Provencher J, O'Hearn L, Visintainer P, et al. Hemotherapy bedside biovigilance involving vital sign values and characteristics of patients with suspected transfusion reactions associated with fluid challenges: can some cases of transfusion-associated circulatory overload have proinflammatory aspects? Transfusion. 2012;52: 2310-20.
Blumberg N, Heal JM, Gettings KF, Phipps RP, Masel D, Refaai MA, et al. An association between decreased cardiopulmonary complications (transfusion-related acute lung injury and transfusion-associated circulatory overload) and implementation of universal leukoreduction of blood transfusions. Transfusion. 2010;50:2738-44.
Collins SR, Blank RS, Deatherage LS, Dull RO. Special article: the endothelial glycocalyx: emerging concepts in pulmonary edema and acute lung injury. Anesth Analg. 2013;117:664-74.
Skeate RC, Eastlund T. Distinguishing between transfusion related acute lung injury and transfusion associated circulatory overload. Curr Opin Hematol. 2007;14:682-7.
Palfi M, Berg S, Ernerudh J, Berlin G. A randomized controlled trial oftransfusion-related acute lung injury: is plasma from multiparous blood donors dangerous? Transfusion. 2001;41:317-22.
Triulzi DJ, Kleinman S, Kakaiya RM, Busch MP, Norris PJ, Steele WR, et al. The effect of previous pregnancy and transfusion on HLA alloimmunization in blood donors: implications for a transfusion-related acute lung injury risk reduction strategy. Transfusion. 2009;49:1825-35.
Saw CL, Hannach B, Petrazsko T, Nickerson P. Blood donors implicated in transfusion-related acute lung injury with patient-specific HLA antibodies are more broadly sensitized to HLA antigens compared to other blood donors. Transfusion. 2013;53:518-25.
Peters AL, Van Stein D, Vlaar AP. Antibody-mediated transfusion-related acute lung injury; from discovery to prevention. Br J Haematol. 2015;170: 597-614.
Muller MC, van Stein D, Binnekade JM, van Rhenen DJ, Vlaar AP. Low-risk transfusion-related acute lung injury donor strategies and the impact on the onset of transfusion-related acute lung injury: a meta-analysis. Transfusion. 2015;55:164-75.
Schmickl CN, Mastrobuoni S, Filippidis FT, Shah S, Radic J, Murad MH, et al. Male-predominant plasma transfusion strategy for preventing transfusion-related acute lung injury: a systematic review. Crit Care Med. 2015;43:205-25.
Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, et al. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intens Care Med. 2012;38: 1573-82.
Toy P, Kleinman SH, Looney MR. Proposed revised nomenclature for transfusion-related acute lung injury. Transfusion. 2017;57:709-13.
Nixon CP, Sweeney JD. Discriminating different causes of transfusion-associated pulmonary edema. Transfusion. 2015;55:1825-8.
Webert KE. Splitting versus lumping: reconsidering the definition of transfusion-related acute lung injury. Transfusion. 2015;55:927-9.
Peters AL, Vlaar AP. Redefining transfusion-related acute lung injury: don't throw the baby out with the bathwater. Transfusion. 2016;56:2384-8.
Andreu G, Boudjedir K, Muller JY, Pouchol E, Ozier Y, Fevre G, et al. Analysis of Transfusion-related acute lung injury and possible transfusion-related acute lung injury reported to the French hemovigilance network from 2007 to 2013. Transfus Med Rev. 2018;32:16-27.
Bux J, Becker F, Seeger W, Kilpatrick D, Chapman J, Waters A. Transfusion-related acute lung injury due to HLA-A2-specific antibodies in recipient and NB1-specific antibodies in donor blood. Br J Haematol. 1996;93:707-13.
Jug R, Anani W, Callum J. A possible case of recipient anti-neutrophil and anti-human leukocyte antigen antibody-mediated fatal reverse transfusion-related acute lung injury. Transfusion. 2021;61:1336-40.
Bayat B, Nielsen KR, Bein G, Traum A, Burg-Roderfeld M, Sachs UJ. Transfusion of target antigens to preimmunized recipients: a new mechanism in transfusion-related acute lung injury. Blood Adv. 2021;5:3975-85.
Benson AB, Moss M, Silliman CC. Transfusion-related acute lung injury (TRALI): a clinical review with emphasis on the critically ill. Br J Haematol. 2009;147:431-43.
Davis A, Mandal R, Johnson M, Makar R, Stowell C, Dzik S. A touch of TRALI. Transfusion 2008;48:541-5.
Kopko PM, Marshall CS, MacKenzie MR, Holland PV, Popovsky MA. Transfusion-related acute lung injury: report of a clinical look-back investigation. JAMA. 2002;287:1968-71.
Win N, Chapman CE, Bowles KM, Green A, Bradley S, Edmondson D, et al. How much residual plasma may cause TRALI? Transfus Med. 2008;18:276-80.
Stroncek DF, Klein HG. Red blood cells, transfusion-related acute lung injury, and lipids: a role for liporeduction? Transfusion. 2011;51:2524-6.
Chi X, Zhi L, Vostal JG. Human platelets pathogen reduced with riboflavin and ultraviolet light do not cause acute lung injury in a two-event SCID mouse model. Transfusion. 2014;54:74-85.
Mounchili A, Leduc S, Archibald C, Miller J, Hyson C. A summary of the Transfusion Transmitted Injuries Surveillance System: 2006 - 2012. Can Commun Dis Rep. 2014;40(18):379-84.
Hillis CM, Shih AW, Heddle NM. Best practices in the differential diagnosis and reporting of acute transfusion reactions. Int J Clin Transfus Med. 2016; 4:1-4.
Croskerry P. From mindless to mindful practice-cognitive bias and clinical decision making. N Engl J Med. 2013;368:2445-8.
Karlamangla A, Tinetti M, Guralnik J, Studenski S, Wetle T, Reuben D. Comorbidity in older adults: nosology of impairment, diseases, and conditions. J Gerontol A Biol Sci Med Sci. 2007;62:296-300.
Badami KG, Joliffe E, Stephens M. Transfusion-associated dyspnea--shadow or substance? Vox Sang. 2015;109:197-200.
Savage WJ, Tobian AA, Savage JH, Wood RA, Schroeder JT, Ness PM. Scratching the surface of allergic transfusion reactions. Transfusion. 2013;53: 1361-71.
Cyr M, Eastlund T, Blais C, Rouleau JL, Adam A. Bradykinin metabolism and hypotensive transfusion reactions. Transfusion. 2001;41:136-50.
Narayan S. The 2020 Annual SHOT Report. Available at: https://www.shotuk.org/wp-content/ uploads/myimages/SHOT-REPORT-2020.pdf. Accessed on 20 November 2021.
Bernard R, Yan M, Ning S, Escorcia A, Pendergrast JM, Cserti-Gazdewich C. Sustained and significant increase in reporting of transfusion reactions with the implementation of an electronic reporting system. Transfusion. 2016;56:1247-8.
Cserti-Gazdewich C, Escorcia A, Pendergrast J, Lieberman L, Skeate R, Lin Y, et al. Platelet transfusion reactions do not occur more often in recipients transfused with apheresis versus buffy coat platelet concentrates. Transfusion. 2016;56:3144-6.
Shih AW, Cohn CS, Delaney M, Fontaine MJ, Martin I, Dunbar NM, et al. The BEST criteria improve sensitivity for detecting positive cultures in residual blood components cultured in suspected septic transfusion reactions. Transfusion. 2019;59:2292-300.
Pendergrast J, Armali C, Cserti-Gazdewich C, Hansen M, Kiss A, Lieberman L, et al. Can furosemide prevent transfusion-associated circulatory overload? Results of a pilot, double-blind, randomized controlled trial. Transfusion. 2019;59:1997-2006.
McVey MJ, Weidenfeld S, Maishan M, Spring C, Kim M, Tabuchi A, et al. Platelet extracellular vesicles mediate transfusion-related acute lung injury by imbalancing the sphingolipid rheostat. Blood. 2021;137:690-701.
Ning S, Heddle NM, Acker JP. Exploring donor and product factors and their impact on red cell post-transfusion outcomes. Transfus Med Rev. 2018;32: 28-35.
Murphree D, Ngufor C, Upadhyaya S, Madde N, Clifford L, Kor DJ, et al. Ensemble learning approaches to predicting complications of blood transfusion. Conf Proc IEEE Eng Med Biol Soc. 2015;2015:7222-5.
