TY - JOUR
T1 - Genetic factors contribute to bleeding after cardiac surgery
AU - Welsby, Ian J.
AU - Podgoreanu, M. V.
AU - Phillips-Bute, B.
AU - Mathew, J. P.
AU - Smith, P. K.
AU - Newman, M. F.
AU - Schwinn, D. A.
AU - Stafford-Smith, M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005
Y1 - 2005
N2 - 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. Patients/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, GPIbα 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.
AB - 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. Patients/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, GPIbα 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.
KW - Cardiopulmonary bypass
KW - Coagulation
KW - Genes
KW - Hematology
KW - Platelets
KW - Thoracic surgery
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U2 - 10.1111/j.1538-7836.2005.01337.x
DO - 10.1111/j.1538-7836.2005.01337.x
M3 - Article
C2 - 15892865
AN - SCOPUS:24944469646
SN - 1538-7933
VL - 3
SP - 1206
EP - 1212
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 6
ER -