The effect of plasma transfusion in an experimental two-hit animal model of transfusion-associated circulatory overload with heart failure

Abstract

Background: Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-related morbidity and mortality. TACO follows a two-hit pathophysiology, where comorbidities like cardiac or renal failure act as the first hit followed by blood transfusion as a second hit. Observational studies suggest that plasma transfusion is more likely to cause TACO than other blood products. We conducted a randomized animal study to gather evidence that plasma transfusion can induce TACO.

Material and methods: As a first hit a large myocardial infarction was created in male Wistar rats. Then animals were randomized to receive 4 units of solvent/ detergent-treated pooled plasma (SDP), fresh frozen plasma (FFP), a colloid control (albumin 5%) or a crystalloid fluid control (Ringer's lactate) (n=10 per group). The primary outcome was the difference between pre- and post-transfusion left-ventricular end diastolic pressure (ΔLVEDP). Secondary outcomes were markers for acute lung injury; lung wet/dry weight ratio, PaO₂/FiO₂ ratio and pulmonary histological assessment.

Results: Pre-transfusion characteristics were similar between groups. ΔLVEDP increased significantly after transfusion with SDP (7.7 mmHg; 4.5-10.5) and albumin (13.0 mmHg; 6.5-15.2), but not after FFP (7.9 mmHg, 1.1; 11.3) compared to infusion with Ringer's lactate (0.6 mmHg; 0.4-2.2), p=0.007, p=0.0005 and p=0.14 respectively. There were no significant differences in ΔLVEDP between groups receiving SDP, FFP or albumin. There was no increase in acute lung injury in any group compared to other groups.

Discussion: Circulatory overload, measured as ΔLVEDP, was induced after transfusion of SDP or albumin, but not after infusion of Ringer's lactate. These results show that the effect of plasma transfusion on ΔLVEDP differs from fluid overload induced by crystalloid infusion. Colloid osmotic pressure may be an important component in the development of TACO and should be a target for future research.

Figure 1

LVEDP peri-transfusion LVEDP values for individual animals are displayed for all randomization groups (A=SDP; B=FFP; C=Ringer’s lactate; D=albumin) SDP: solvent-detergent pooled plasma; FFP: fresh frozen plasma.

Figure 2

ΔLVEDP is calculated as post-transfusion LVEDP – pre-transfusion LVEDP SDP: solvent-detergent pooled plasma; FFP: fresh frozen plasma; *p: 0.007; ** p: 0.0005.

Figure 3

Pulmonary outcomes Individual values are displayed, median values for each group are indicated with black lines (A=pulmonary wet/dry weight ratio, B=paO₂/FiO₂(P/F) ratio before termination of the experiment, C=histopathological score) SDP: solvent-detergent pooled plasma FFP: fresh frozen plasma.