PAI-1 gene: pharmacogenetic association of 4G/4G genotype with bleeding after cardiac surgery--pilot study.
OBJECTIVE
To investigate whether the 4G/4G genotype of the PAI-1 gene is associated with bleeding after cardiac surgery and whether it may influence the use of antifibrinolytic drugs.


METHODS
After a case-control association study to compare the distribution of genotypes of the 4G/5G polymorphism of the PAI-1 gene (4G/4G, 4G/5G and 5G/5G) between cardiac surgery patients (n = 260) and nonhospitalized age-matched controls (n = 111), we have evaluated the possible association of genotype homozygous 4G/4G (considered procoagulant) in two cohorts of cardiac surgery patients (treated with aprotinin or tranexamic acid) with postoperative bleeding and transfusion requirements. Chest tube output was measured at 6 h and 24 h and then total blood output. Genotypes were typed using restriction fragment length polymorphism analysis.


RESULTS
The PAI-1 4G/4G genotype was not associated with bleeding except in the subgroup of patients treated with aprotinin in whom blood loss was significantly lower than in nonhomozygous 4G/4G patients at 6 h and 24 h [mean 135.9 ml (SD 101.8 ml) vs. mean 227.6 ml (SD 218.2 ml), P < 0.05; mean 314.5 ml (SD 180.3) vs. mean 482.7 ml (SD 349.8), P < 0.05, respectively]. Moreover, in homozygous 4G/4G patients, aprotinin was independently associated with lower total blood loss and also tended to require less transfusion (26.3 vs. 47.2%; 95% confidence interval, 0.3-2.7; P = 0.2). Only the European system of cardiac-operative risk evaluation score of at least 6 and therapy with platelet antiaggregants were associated with bleeding in the general patient population.


CONCLUSIONS
The 4G/4G genotype of the PAI-1 gene was associated with less bleeding after cardiac surgery only in the subgroup of patients treated with aprotinin.
Sirgo
Gonzalo
G
Intensive Care Department, Joan XXIII University Hospital, University Rovira i Virgili, Pere Virgili Health Institute, CIBER Enfermedades Respiratorias, Tarragona, Spain. gsirgoluanco@yahoo.es
Morales
Pablo
P
Rello
Jordi
J
D000368:Aged; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D007611:Aprotinin / Q000627:therapeutic use; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000379:methods; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010865:Pilot Projects; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D019106:Postoperative Hemorrhage / Q000235:genetics / Q000517:prevention & control*; D014148:Tranexamic Acid / Q000627:therapeutic use
D000933:Antifibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D014148:Tranexamic Acid; D007611:Aprotinin