Postoperative bleeding in cardiac surgery: The role of tranexamic acid in patients homozygous for the 5G polymorphism of the plasminogen activator inhibitor-1 gene

Intensive Care Department, University Hospital of the Canary Islands, University of La Laguna, Tenerife, Spain.
Anesthesiology (Impact Factor: 5.88). 05/2008; 108(4):596-602. DOI: 10.1097/ALN.0b013e318167aecc
Source: PubMed


Plasminogen activator inhibitor 1 (PAI-1) attenuates the conversion of plasminogen to plasmin. Polymorphisms of the PAI-1 gene are associated with varying PAI-1 levels and risk of prothrombotic events in nonsurgical patients. The purpose of this study, a secondary analysis of a clinical trial, was to investigate whether PAI-1 genotype affects the efficacy of tranexamic acid (TA) in reducing postoperative chest tube blood loss of patients undergoing cardiopulmonary bypass.
Fifty patients were classified according to PAI-1 genotype (4G/4G, 4G/5G, or 5G/5G). Twenty-four received 2 g TA before and after cardiopulmonary bypass, whereas 26 received placebo. The authors recorded data related to coagulation, fibrinolysis, and bleeding before surgery, at admission to the intensive care unit (0 h), and 4 and 24 h later.
In patients not receiving TA, those with the 5G/5G genotype had significantly higher chest tube blood loss and transfusion requirements compared with patients with the other genotypes at all time points. Patients with the 5G/5G genotype receiving TA showed significantly lower blood loss compared with the placebo group. There were no significant differences in blood loss or transfusion requirements between patients with the 4G/4G genotype when TA was used.
Plasminogen activator inhibitor-1 5G/5G homozygotes who did not receive TA showed significantly greater postoperative bleeding than patients with other PAI-1 genotypes. 5G/5G homozygotes who received TA showed the greatest blood-sparing benefit.

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    • "These include the surgery per se as well as effects of the cardiopulmonary bypass (CPB) on the coagulation and the inflammation cascades, and their cross-reactions with the fibrinolytic – and the kinin-kallikrein systems [1-3]. During the last few years, increasing attention has been paid to reports demonstrating the influence of the fibrinolytic system on increased bleeding, particularly after cardiac surgery employing CPB [1,4-6]. "
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    ABSTRACT: Background Enhanced bleeding remains a serious problem after cardiac surgery, and fibrinolysis is often involved. We speculate that lower plasma concentrations of plasminogen activator inhibitor – 1 (PAI-1) preoperatively and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex postoperatively might predispose for enhanced fibrinolysis and increased postoperative bleeding. Methods Totally 88 adult patients (mean age 66 ± 10 years) scheduled for cardiac surgery, were enrolled into a prospective study. Blood samples were collected pre-operatively, on admission to the recovery and at 6 and 24 hours postoperatively. Patients with a surgical bleeding that was diagnosed during reoperation were discarded from the study. The patients were allocated to two groups depending on the 24-hour postoperative chest tube drainage (CTD): Group I > 500ml, Group II ≤ 500ml. Associations between CTD, PAI-1, t-PA/PAI-1 complex and D-dimer were analyzed with SPSS. Results Nine patients were excluded because of surgical bleeding. Of the 79 remaining patients, 38 were allocated to Group I and 41 to Group II. The CTD volumes correlated with the preoperative plasma levels of PAI-1 (r = − 0.3, P = 0.009). Plasma concentrations of preoperative PAI-1 and postoperative t-PA/PAI-1 complex differed significantly between the groups (P < 0.001 and P = 0.012, respectively). Group I displayed significantly lower plasma concentrations of fibrinogen and higher levels of D-dimer from immediately after the operation and throughout the first 24 hours postoperatively. Conclusions Lower plasma concentrations of PAI-1 preoperatively and t-PA/PAI-1 complex postoperatively leads to higher plasma levels of D-dimer in association with more postoperative bleeding after cardiac surgery.
    BMC Anesthesiology 10/2012; 12(1):27. DOI:10.1186/1471-2253-12-27 · 1.38 Impact Factor
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    ABSTRACT: Variation in bleeding in the perioperative period is a complex and multifactorial event associated with immediate and delayed consequences for the patient and health care resources. Little is known about the complex genetic influences on perioperative bleeding. With the discovery of multiple variations in the human genome and ever-growing databases of well-phenotyped surgical patients, better identification of patients at risk of bleeding is becoming a reality. In this review, polymorphisms in the platelet receptor genes, plasminogen activator inhibitor, and angiotensin genes among others will be discussed. We will explore the nature, effects, and implications of the genetics that influence perioperative bleeding above and beyond surgical bleeding, particularly in cardiac surgery.
    American Journal of Hematology 09/2008; 83(9):732-7. DOI:10.1002/ajh.21205 · 3.80 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    European Journal of Anaesthesiology 05/2009; 26(5):404-11. DOI:10.1097/EJA.0b013e3283240412 · 2.94 Impact Factor
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