Pathophysiological concepts in transfusion-associated circulatory overload

Pulmonary transfusion complications are the leading cause of transfusion related morbidity and mortality. The most important pulmonary transfusion reactions are transfusion-related lung injury (TRALI) and transfusion-associated circulatory overload (TACO). TACO is defined as acute or worsening respiratory comprise or pulmonary edema within 12 hours following transfusion accompanied by cardiovascular changes. TACO is suggested to be a consequence of volume overload and is characterized by transudative protein poor edema. TACO’s pathophysiology is not completely understood. There is evidence TACO follows a two-hit model. The first hit consists of patient comorbidities resulting in volume incompliance. The second hit is the transfusion itself which increases the intravascular volume and leads to volume overload. When the cardiovascular system is unable to compensate for this additional volume, fluid is forced out of the vessels, ultimately leading to pulmonary edema and respiratory failure. In this thesis we have investigated second hit mechanisms that could contribute to the development of TACO. These include changes in colloid osmotic pressure, the endothelial glycocalyx layer and inflammation as well as the impact of storage lesion of blood products. We hypothesized that multiple mechanisms can contribute to the development of TACO and that TACO is most likely a result of a combination of increased hydrostatic pressure and diminished endothelial barrier function.