Original article

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

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Key words: transfusion reaction, plasma, pulmonary edema, animal models, transfusion-associated circulatory overload
Publication Date: 2022-11-04

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. 

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Authors

Esther B. Bulle - Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

Robert B. Klanderman - Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

Marit B. de Wissel - Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

Joris J.T.H. Roelofs - Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Microcirculation, University of Amsterdam, Amsterdam, the Netherlands

Denise P. Veelo - Department of Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

Charissa E. van den Brom - Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Anesthesiology, Amsterdam UMC, VU University, Amsterdam, the Netherlands

Rick Kapur - Sanquin Research, Department of Experimental Immunohematology, Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

Alexander P.J. Vlaar - Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

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