Association of the 98T ELAM-1 Polymorphism With Increased Bleeding After Cardiac Surgery
published online 07 January 2010.
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.
Design
Prospective, observational study.
Setting
Single, tertiary referral university heart center.
Participants
Adult patients undergoing aortocoronary surgery with cardiopulmonary bypass.
Interventions
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 1β 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.
Measurements and Main 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.
⁎Department of Anesthesiology, Duke University Medical Center, Durham, NC
†Department of Surgery, Duke University Medical Center, Durham, NC
‡Department of Pharmacology/Cancer Biology, Duke University Medical Center, Durham, NC
Address reprint requests to Ian J. Welsby, MBBS, Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC 27710
Funded in part by NIH grant AG17556 (D.A.S.), AHA grants 0120492U (M.V.P.), 0256342U (J.P.M.), 9970128N (M.F.N.); an educational grant from Bayer Pharmaceuticals Corporation (I.J.W.); and the Duke Clinical Research Centers Program (NIH grant M01-RR-30). D.A.S. is a senior fellow in the Duke Center for the Study of Aging and Human Development.
ABSTRACT