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

Abstract

Background/objectives 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. Materials/Methods 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). Results 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). Conclusions Only half of cardiopulmonary TRs constituted high certainty diagnoses. Nevertheless, cardiopulmonary TRs and suspected BaCon marked higher VISTR mortality with shorter TTDs. Short (<1 week) TTDs in TAD, BaCon or TRALI imply either contributing roles in death, treatment refractoriness and/or applicable TR susceptibilities in the dying.

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

“…[17][18][19][20][21][22] Given the disproportionate extent of coding-uncertainty in CRTRs, deep/unbiased clinicolaboratory profiling may identify unsuspected pathophysiologic mediators, and consequently enable re-classification of CRTRs that have either been coded as uncertain, incorrect, or incomplete diagnoses or as members of the pragmatic exclusion category known as transfusion-associated dyspnea (TAD) (Figure 2). 16 Interestingly, TACO appears to be more than mere circulatory overload, exhibiting inflammation and/or pyrexia in 1/3 rd of cases, and a non-leukoreduction association. 4,[23][24][25][26] Endothelial stretch may advance transudation to exudation and cloud the difference between TACO and TRALI.…”

“…[9][10][11] Taken together, CRTRs account for the majority of transfusion-related fatalities, though their true scope in all-cause morbidity and mortality remains unknown. [12][13][14][15][16]…”

“…52,53 Despite these facts, few reports describe the proportion or frequency of adverse transfusion events presenting as two or more simultaneous injuries. 16,23 The uncertain roots of TAD TAD is a final diagnosis-of-exclusion in hemovigilance if neither the underlying condition nor a specifically defined harm account for the suspected CRTR. As a basket category guarding against inflated tallies of TRALI or TACO (for those cases falling short in criteria and/or severity), TAD therefore shelters unknown proportions of these and other states, including the possibility of a unique injury group with its own pathogenesis.…”

“…61 Whereas uncertainty (i.e., confidence in the provisional diagnosis deemed not better than "possible" (or simply "unable to rule out") runs at roughly 10%, a distinct rate (of 63%) in CRTR was the primary concern and justification for a targeted and deeper-testing approach. 16 The aspirational hypothesis was to reduce CRTR baseline uncertainty ranges from 40-60% to 20-45%. At α 0.05 and β 0.90, by paired Chi-square/McNemar's test for CRTRs prior to and after systematic TADPOL-specified data enrichment, the sample size requirement was 53 to 110 (Table 1).…”

Potential Predictors for Deterioration of Renal Function After Transfusion

“…8 It is difficult to judge whether the transfusion of a specific pRBC unit results in a side effect in a particular patient. 9 Furthermore, it is difficult to evaluate whether a specific transfusion causes an adverse reaction or whether a patient develops a complication irrespective of the unit of RBC transfused.…”