Factors Associated with Mortality in Transfusion
Associated Circulatory Overload
Soni L, Saeed S, Cserti-Gazdewich C, McVey MJ
Background. Transfusion associated circulatory overload (TACO) surpassed transfusion-related
acute lung injury (TRALI) making it the leading cause of death amongst respiratory transfusion
reactions. Aims. Here we retrospectively determine risk factors associated with TACO from a
hemovigilance database. Methods. Non-pregnant adults (age > 18 years) with possible to definite
TACO reactions from 3 quaternary urban hospitals from 2010-2020 were analyzed
(REB#1000080295). Of 407 suspected TACOs, 19 were ruled out, while 17 were excluded as
massive hemorrhages. To assess TACO risk factors the following parameters were analyzed: age
(years), sex, received-red blood cells (RBC)s (Y/N, platelets- (Y/N), plasma- (Y/N), TACO
severity (1: minor [required no treatment or only agents that nursing can provide from automatic
orders], 2: moderate [required MD review +/- unplanned treatment], 3: severe [escalation in care/
disposition change now needing major supplemental oxygen], and 4: life-threatening/fatal
[requirement for lifesaving care such as intubation]), grade (high severity: 3+4; or low: 1+2), 28
day mortality, in-hospital mortality and new ICU admission. TACO reactions were judged on the
confidence spectrum as either ruled out/doubtful, possible, probable, most likely, or definite per
previously described paradigms. The potential additional diagnosis of TRALI was also noted when
applicable. Descriptive statistical tests were conducted with SPSS software. A. p≤0.05 was
considered statistically significant. Results. Of the 371 TACO cases (63 ± 16.8 years; mean ± S.D.)
overall in-hospital mortality (IHM) was 17.5% and the 28-day mortality (28M) was 12.9%. Both
28M (p=0.04) and IHM (p=0.04) were significantly different between the 179 males and 192
females. The odds of surviving were 0.55 times lower in males ( 95% CI: 0.32 – 0.95). Severity
grading revealed 31 (8.4%), 83 (22.4%), 204 (55%), and 53 (14%) life-threatening, severe,
moderate, and mild reactions respectively. Platelet-involving encounters were associated with
severe TACO. Among cases, 274 (73.9%), 121 (32.6%), and 28 (7.5%) involved RBC, platelets,
or plasma respectively. Mortality data were available for 369 patients. Platelet transfusion was
found to be associated with both 28M (p=0.035) and IHM (p=0.013). Survival odds were 1.97
times greater (95% CI: 1.14-3.40) in patients with no platelet transfusion compared to those
platelet-transfused. We assessed concomitant TRALI as a possible confounder as we found 29
TACO cases that had an additional diagnosis of TRALI which was also associated with mortality
(p<0.05). Of interest 10 of those were transfused platelets. New ICU admission (data available for
356 cases) amongst the survivors and non-survivors was also found to be significantly associated
with 28M (p =0.001) and IHM (p=0.00). Discussion. TACO remains underrecognized. While
TACO may generally associate often with RBC transfusion, here we show TACO mortality
associations with platelet transfusions, male recipients, and disposition escalation to the ICU. Our
findings are preliminary and limited by the retrospective and uncontrolled nature of the study.
Gaps included details on circulatory fluid status as well as renal or cardiac disease. Future
prospective mechanistic and larger epidemiological studies are needed to confirm our findings.
Potential sex differences and product-related factors may influence not only the incidence but also
the severity (i.e. mortality) of TACO.