This secondary analysis of a prospective cohort of critically ill patients who were transfused in the medical ICU confirmed the common occurrence of TACO. Positive fluid balance, larger volume of transfusion, greater plasma transfusion volume, and a faster transfusion rate predicted development of TACO. A comparison of TACO cases and randomly selected controls identified left ventricular dysfunction and FFP ordered for the reversal of anticoagulation therapy predicted the development of TACO before the onset of transfusion.
Our findings confirmed TACO is a common transfusion-related complication in critically ill patients. The incidence of TACO in this report (6%) is consistent with existing literature which notes an incidence ranging from 1 to 8 percent3,6,20
. Our previous study noted a higher rate of TACO (1 in 356) than TRALI (1 in 534 per unit) per unit of blood component transfused3
. This is much higher than the incidence rate in a recent hemovigilance report from Ireland (1/10,000 of all components)21
. In addition to a different study population (critically ill patients vs all transfused patients), the major difference is likely a result of different identification methods (prospective observation vs passive reporting). Recent reports noted TACO to be the fifth most common cause of death resulting from transfusion in the United States with an estimated mortality ranging from 5–15%22
. Although the observed mortality is mostly due to underlying illness, rather than TACO per se5
, this complication does result in significant morbidity and increase the length of hospital stay5
Despite its importance, TACO has received surprisingly little attention when compared with other transfusion-related complications such as infection and TRALI 9
. A single report associated age with the occurrence of TACO in an orthopedic surgery population. The mean age of patients who developed TACO in this investigation was 84 years. In contrast, the median age of our TACO patients was 73 years, similar to recent reports from Robillard23
. This difference is explained by the differing study populations as patients undergoing total hip or knee replacements are more likely to be of advanced age than an unselected ICU population.
Left ventricular dysfunction is believed to be a risk factor for TACO with previous estimates reporting it’s presence in 73% (131) of TACO cases21
. TACO often occurs in elderly patients6
and those with compromised cardiac function24
. FFP remains as the first-line therapy for the urgent/emergent reversal of anticoagulant therapy in the US and American Society of Anesthesiologist’s recommended dose of FFP is 10–15 ml per kg25
, which is similar to dosing recommendations provided by the British Committee on Standards in Haematology26
. This large volume of FFP (frequently 1 – 2 liters) is clearly undesirable in patients at risk of TACO. Our unmatched univariate and multivariate analysis confirmed cardiovascular dysfunction and FFP use for reversal of anticoagulant therapy before transfusion as important predictors of TACO. Lower volume alternatives to FFP need to be evaluated in future TACO prevention trials. Further, our results identified blood component transfusion rate, cumulative fluid balance, cumulative transfusion volume, and volume of plasma transfused as significant predictors of TACO, independent of pre-existing cardiovasucular disease or left ventricular dysfunction. The average transfusion rate in patients who developed TACO was 225 (IQR 135–350) ml/hour compared to 164 (IQR 99–206) ml/hour in matched controls. Although the AABB Technical Manual27
recommends an infusion rate of 150 to 300 mL per hour for red blood cell transfusion and faster rates for plasma and platelets components, our data suggest slower transfusion rates should be observed when possible. In addition to the faster infusion rates, patients who developed TACO also received a significantly larger volume of blood product. Previous reports have described TACO following 1–4 units of administered blood product3,20
. A smaller volume of blood component therapy (1–2 units) was associated with TACO in the study of Popovsky and colleagues as well6
. Indeed, even a single transfused unit may be sufficient to precipitate the reaction in a susceptible recipient.1,28
Pre-transfusion diuretic therapy was not found to be protective. This is similar to the findings of Andrea21
where 40% of patients received diuretics but still progressed to TACO. However, infrequent use of diuretics before transfusion make it difficult to determine the benefit of this prevention strategy.
There are a number of potential limitations with this investigation that deserve mention. To begin, the study was conducted in the ICU of a single tertiary center and the results are unlikely to be generalizable to non-ICU patients. In addition, the sample size was limited by the TACO cases observed in the initial prospective cohort study. As a result, the present study was not adequately powered to detect more subtle associations. Although the matched study design minimized confounding from underlying cardiovascular disease and left ventricular dysfunction, the observational nature of this investigation also has the potential for multiple additional measured and unmeasured confounding effects.
In conclusion, TACO occurs frequently after transfusion in critically ill patients. Transfusion volume and the rate of blood component administration appear to be important risk factors for development of TACO in patients with similar baseline characters. Baseline cardiovascular function and FFP ordered for the reversal of anticoagulant therapy are strong predictors of TACO before the onset of transfusion.