Association of the 98T ELAM-1 polymorphism with increased bleeding after cardiac surgery.

Published

Journal Article

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 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. 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.

Full Text

Duke Authors

Cited Authors

  • Welsby, IJ; Podgoreanu, MV; Phillips-Bute, B; Morris, R; Mathew, JP; Smith, PK; Newman, MF; Schwinn, DA; Stafford-Smith, M; Perioperative Genetics and Safety Outcomes Study Investigative Team,

Published Date

  • June 2010

Published In

Volume / Issue

  • 24 / 3

Start / End Page

  • 427 - 433

PubMed ID

  • 20056442

Pubmed Central ID

  • 20056442

Electronic International Standard Serial Number (EISSN)

  • 1532-8422

Digital Object Identifier (DOI)

  • 10.1053/j.jvca.2009.10.030

Language

  • eng

Conference Location

  • United States