title: Red Cell Transfusion-Associated Hemolysis in Cardiac Surgery: An Observational Cohort Study.
abstract: Red cell viability is impaired during storage, resulting in excess hemolysis during storage and after transfusion. As a result, transfusions may oversaturate the hemoglobin clearance pathways, resulting in cell-free hemoglobin and iron toxicity in susceptible patients, such as those undergoing cardiac surgery with cardiopulmonary bypass. To explore this hypothesis, we assessed the relationship of red cell transfusions with cell-free hemoglobin and transferrin saturation levels in a consecutive cohort of cardiac surgical patients.
  
  
  
  Laboratory measures of hemolysis were obtained in consecutive cardiac surgical patients 15 to 30 minutes after bypass. Multivariable regression models controlling for important confounders were constructed to determine the independent relationship of red cell transfusions during bypass with cell-free hemoglobin and transferrin saturation levels post-bypass, analyzed as continuous variables (linear regression) and categorized at the 90th percentiles (logistic regression).
  
  
  
  Of the 543 included patients, 82 (15.1%) received red cell transfusions during bypass (median 1; interquartile range 1-2 units). Cell-free hemoglobin was detected in all patients (mean 11.3; standard deviation ± 9.3; 90th percentile 18 μmol/L), and transferrin saturations were relatively high (mean 41 ± 19%; 90th percentile 66%). After controlling for confounders, transfusions were not associated with cell-free hemoglobin (P > .25 in linear and logistic regression) but were directly associated with transferrin saturation levels (P < .001 in linear and logistic regression). Transfused patients had a 6.2-fold (95% confidence interval: 2.4-16.1) risk-adjusted increase in the odds of having high (>66%) transferrin saturation levels.
  
  
  
  The findings support the hypothesis that transfusion-related adverse events may be in part caused by the excessive hemolysis of transfused red cells, which can lead to acute iron overload and related toxicity. This suggests that strategies aimed at avoiding or mitigating transfusion-related acute iron overload may improve the safety of red cell transfusions.
authors.affiliation: From the *Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, and †Department of Clinical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; ‡Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada; §Centre for Innovation, Canadian Blood Services, Edmonton, Canada; ‖Department of Clinical Biochemistry, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada; and ¶Department of Surgery, Division of Cardiac Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Karkouti
authors.forename: Jeannie L
authors.initials: JL
authors.lastname: Callum
authors.forename: Jason P
authors.initials: JP
authors.lastname: Acker
authors.forename: Paul
authors.initials: P
authors.lastname: Yip
authors.forename: Vivek
authors.initials: V
authors.lastname: Rao
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D014168:Transferrin