Supernatant of aged erythrocytes causes lung inflammation and coagulopathy in a "two-hit" in vivo syngeneic transfusion model.
BACKGROUND
Transfusion of erythrocytes is associated with increased morbidity in certain patient groups. Storage time of erythrocytes may contribute to respiratory complications. Using a syngeneic in vivo transfusion model, we investigated whether transfusion of stored rat erythrocytes causes lung injury in healthy and in lipopolysaccharide-primed rats in a "two-hit" model of lung injury.


METHODS
Rats were infused with aged rat erythrocytes (14 days of storage) and washed aged erythrocytes or supernatant of aged erythrocytes. Controls received fresh rat erythrocytes (0 days of storage) or saline. In the "two-hit" model of lung injury, lipopolysaccharide was used as a "first hit" before transfusion. Rat and control human erythrocyte products were analyzed for lysophosphatidylcholine accumulation.


RESULTS
In healthy rats, transfusion of aged erythrocytes caused mild pulmonary inflammation but no coagulopathy. In lipopolysaccharide-pretreated rats, transfusion of aged erythrocytes augmented lung injury by inducing coagulopathy, both in the pulmonary and systemic compartment, when compared with transfusion with fresh erythrocytes. When transfused separately, supernatant of aged erythrocytes, but not washed aged erythrocytes, mediated coagulopathy in the "two-hit" model. Analysis of the supernatant of aged erythrocytes (rat and human) showed no lysophosphatidylcholine accumulation.


CONCLUSIONS
Transfusion of aged erythrocytes induces lung injury in healthy rats. In a "two-hit" model, injury induced by aged erythrocytes was characterized by coagulopathy and was abrogated by washing. Washing of aged erythrocytes may decrease pulmonary complications in patients with an inflammatory condition who are exposed to a blood transfusion.
Department of Intensive Care Medicine, Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, Amsterdam, The Netherlands. a.p.vlaar@amc.uva.nl
Alexander P J
AP
Vlaar
Jorrit J
JJ
Hofstra
Marcel
M
Levi
Willem
W
Kulik
Rienk
R
Nieuwland
Anton T J
AT
Tool
Marcus J
MJ
Schultz
Dirk
D
de Korte
Nicole P
NP
Juffermans
D055371:Acute Lung Injury / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004905:Erythrocyte Aging; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D011014:Pneumonia / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage
D015415:Biomarkers; D008070:Lipopolysaccharides; D012965:Sodium Chloride