title: Genetic factors contribute to bleeding after cardiac surgery.
abstract: BACKGROUND
  Postoperative bleeding remains a common, serious problem for cardiac surgery patients, with striking inter-patient variability poorly explained by clinical, procedural, and biological markers.
  
  
  OBJECTIVE
  We tested the hypothesis that genetic polymorphisms of coagulation proteins and platelet glycoproteins are associated with bleeding after cardiac surgery.
  
  
  METHODS
  Seven hundred and eighty patients undergoing aortocoronary surgery with cardiopulmonary bypass were studied. Clinical covariates previously associated with bleeding were recorded and DNA isolated from preoperative blood. Matrix Assisted Laser Desorption/Ionization, Time-Of-Flight (MALDI-TOF) mass spectroscopy or polymerase chain reaction were used for genotype analysis. Multivariable linear regression modeling, including all genetic main effects and two-way gene-gene interactions, related clinical and genetic predictors to bleeding from the thorax and mediastinum.
  
  
  RESULTS
  Nineteen candidate polymorphisms were assessed; seven [GPIaIIa-52C>T and 807C>T, GPIb alpha 524C>T, tissue factor-603A>G, prothrombin 20210G>A, tissue factor pathway inhibitor-399C>T, and angiotensin converting enzyme (ACE) deletion/insertion] demonstrate significant association with bleeding (P < 0.01). Adding genetic to clinical predictors results improves the model, doubling overall ability to predict bleeding (P < 0.01).
  
  
  CONCLUSIONS
  We identified seven genetic polymorphisms associated with bleeding after cardiac surgery. Genetic factors appear primarily independent of, and explain at least as much variation in bleeding as clinical covariates; combining genetic and clinical factors double our ability to predict bleeding after cardiac surgery. Accounting for genotype may be necessary when stratifying risk of bleeding after cardiac surgery.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. welsb001@mc.duke.edu
authors.forename: I J
authors.initials: IJ
authors.lastname: Welsby
authors.forename: M V
authors.initials: MV
authors.lastname: Podgoreanu
authors.forename: B
authors.initials: B
authors.lastname: Phillips-Bute
authors.forename: J P
authors.initials: JP
authors.lastname: Mathew
authors.forename: P K
authors.initials: PK
authors.lastname: Smith
authors.forename: M F
authors.initials: MF
authors.lastname: Newman
authors.forename: D A
authors.initials: DA
authors.lastname: Schwinn
authors.forename: M
authors.initials: M
authors.lastname: Stafford-Smith
mesh_terms: D000368:Aged; D001779:Blood Coagulation Factors / Q000235:genetics; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000209:etiology / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000209:etiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001779:Blood Coagulation Factors; D010980:Platelet Membrane Glycoproteins