Association of the 98T ELAM-1 polymorphism with increased bleeding after cardiac surgery.
OBJECTIVE
Hemorrhage continues to be a major problem after cardiac surgery despite the routine use of antifibrinolytic drugs, with striking inter-patient variability poorly explained by already known risk factors. The authors tested the hypothesis that genetic polymorphisms of inflammatory mediators and cellular adhesion molecules are associated with bleeding after cardiac surgery.


METHODS
Prospective, observational study.


METHODS
Single, tertiary referral university heart center.


METHODS
Adult patients undergoing aortocoronary surgery with cardiopulmonary bypass.


METHODS
Patients (n = 759) had 10 mL of blood drawn preoperatively and genomic DNA isolated then genotyped for 17 polymorphisms in 7 candidate genes: tumor necrosis factor, interleukins 1beta and 6, interleukin 1 receptor antagonist, intercellular adhesion molecule-1 (ICAM-1), P-selectin and endothelial leucocyte adhesion molecule-1 (E-selectin). Multivariate analyses were used to relate clinical and genetic factors to bleeding and transfusion.


RESULTS
The 98G/T polymorphism of the E-selectin gene was independently associated with bleeding after cardiac surgery (p = 0.002), after adjusting for significant clinical predictors (patient size and baseline hemoglobin concentration). There was a gene dose effect according to the number of minor alleles in the genotype; carriers of the minor allele bled 17% (GT) and 54% (TT) more than wild type (GG) genotypes, respectively (p = 0.01). Carriers of the minor allele also had longer activated partial thromboplastin times (p = 0.0023) and increased fresh frozen plasma transfusion (p = 0.03) compared with wild type.


CONCLUSIONS
The authors found a dose-related association between the 98T E-selectin polymorphism and bleeding after cardiac surgery, independent of and additive to standard clinical risk factors.
Welsby
Ian J
IJ
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. welsb001@mc.duke.edu
Podgoreanu
Mihai V
MV
Phillips-Bute
Barbara
B
Morris
Richard
R
Mathew
Joseph P
JP
Smith
Peter K
PK
Newman
Mark F
MF
Schwinn
Debra A
DA
Stafford-Smith
Mark
M
D000368:Aged; D000483:Alleles; D001772:Blood Cell Count; D001778:Blood Coagulation Disorders / Q000097:blood; D001780:Blood Coagulation Tests; D001803:Blood Transfusion; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D015815:Cell Adhesion Molecules / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000235:genetics*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011110:Polymorphism, Genetic; D019106:Postoperative Hemorrhage / Q000453:epidemiology* / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors; D016896:Treatment Outcome
D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D004247:DNA