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      PAI-1 and t-PA/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass

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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.

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          Most cited references29

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          European system for cardiac operative risk evaluation (EuroSCORE)

          European Journal of Cardio-Thoracic Surgery, 16(1), 9-13
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            Activation of the hemostatic system during cardiopulmonary bypass.

            Cardiopulmonary bypass (CPB) is a unique clinical scenario that results in widespread activation of the hemostatic system. However, surgery also results in normal increases in coagulation activation, platelet activation, and fibrinolysis that are associated with normal wound hemostasis. Conventional CPB interferes with normal hemostasis by diluting hemostatic cells and proteins, through reinfusion of shed blood, and through activation on the bypass circuit surface of multiple systems including platelets, the kallikrein-kinin system, and fibrinolysis. CPB activation of the kallikrein-kinin system increases activated factor XIIa, kallikrein, bradykinin, and tissue plasminogen activator levels, but has little effect on thrombin generation. Increased tissue plasminogen activator and circulating fibrin result in increased plasmin generation, which removes hemostatic fibrin. The nonendothelial surface of the bypass circuit, along with circulating thrombin and plasmin, lead to platelet activation, platelet receptor loss, and reduced platelet response to wounds. In this review, we highlight the major mechanisms responsible for CPB-induced activation of the hemostatic system and examine some of the markers described in the literature. Additionally, strategies used to reduce this activation are discussed, including limiting cardiotomy suction, increasing circuit biocompatibility, antithrombin supplementation, and antifibrinolytic use. Determining which patients will most benefit from specific therapies will ultimately require investigation into genetic phenotypes of coagulation protein expression. Until that time, however, a combination of approaches to reduce the hemostatic activation from CPB seems warranted.
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              Plasminogen activator inhibitor type 1 deficiency.

              Plasminogen activator inhibitor type 1 (PAI-1) is an important component of the coagulation system that down-regulates fibrinolysis in the circulation. Reduced PAI-1 levels may result in increased fibrinolysis and an associated bleeding diathesis. Clear documentation of PAI-1 deficiency as a cause of a bleeding disorder has been rare. PAI-1 was initially identified in the 1980s, and the first reported case of PAI-1 deficiency appeared in 1989. Several reports followed, although only two identified an underlying genetic defect. These reports of PAI-1 deficiency suggest that affected individuals exhibit mild to moderate bleeding symptoms, including epistaxis, menorrhagia, and delayed bleeding after trauma or surgical procedures. Affected individuals rarely exhibit spontaneous bleeding events commonly seen in other procoagulant deficiencies. The majority of bleeding events are controlled with antifibrinolytic agents, such as tranexamic acid and epsilon-aminocaproic acid. A major issue that contributes to difficulty in establishing an accurate diagnosis of PAI-1 deficiency is that the activity assay is accurate in detection of elevated levels but not at the lowest range. Reported normal ranges begin at zero, thereby making a deficiency state because of a dysproteinaemia difficult to distinguish from that of a normal unaffected individual. Although the antigen assay may be helpful in some circumstances, it assists only with complete quantitative disorders. Because of lack of standardized commercially available PAI-1 activity assay sensitive in the lowest range, the true prevalence of this rare condition has not been established.
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                Author and article information

                Journal
                BMC Anesthesiol
                BMC Anesthesiol
                BMC Anesthesiology
                BioMed Central
                1471-2253
                2012
                30 October 2012
                : 12
                : 27
                Affiliations
                [1 ]Department of Anaesthesiology and Cardiac surgery, Pauls Stradins Clinical University Hospital, Pilsonu street 13, Riga, Latvia
                [2 ]Department of Anaesthesiology and Reanimatology, Riga Stradins University, Dzirciema street 16, Riga, Latvia
                [3 ]Clinical Immunology Centre, Pauls Stradins Clinical University Hospital, Pilsonu street 13, Riga, Latvia
                [4 ]Department of Infectology and Dermatology, Riga Stradins University, Dzirciema street 16, Riga, Latvia
                [5 ]Anaesthesia and Critical Care Research Group, Department of Clinical Medicine (Anaesthesiology), Faculty of Medicine, University of Tromsø, MH-Breivika, Tromsø, 9038, Norway
                [6 ]Department of Anaesthesiology, University Hospital of North Norway, Sykehusveien 38, Tromsø, 9038, Norway
                Article
                1471-2253-12-27
                10.1186/1471-2253-12-27
                3524048
                23110524
                8b4fe251-6bb6-49ae-8842-0f627c447be0
                Copyright ©2012 Ozolina et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 February 2012
                : 23 October 2012
                Categories
                Research Article

                Anesthesiology & Pain management
                fibrinolysis,plasminogen activator inhibitor,cardiac surgery,tissue plasminogen activator

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