Fibrin formation is more impaired than thrombin generation and platelets immediately following cardiac surgery

Department of Anaesthesiology and Intensive Care, Salzburger Landeskliniken SALK, Salzburg, Austria.
Thrombosis Research (Impact Factor: 2.45). 03/2011; 128(3):277-82. DOI: 10.1016/j.thromres.2011.02.022
Source: PubMed


Cardiac surgery performed on cardio-pulmonary bypass (CPB) may be complicated by coagulopathy and bleeding. This prospective observational study investigated the CPB-induced changes in thrombin generation, fibrin formation, and in the platelet component of the whole blood clot elasticity. The effects of haemostatic therapy with fresh frozen plasma (FFP) and platelet concentrate on these parameters were also evaluated.
In 90 cardiac surgery patients, thrombin generation was measured using the calibrated automated thrombogram, fibrin formation was assessed as the maximum clot elasticity of the fibrin-based clot in the thromboelastometry FIBTEM test (MCE(FIBTEM)), and the platelet component was defined as the difference in maximum elasticity between the whole blood clot obtained through extrinsic activation and the fibrin-based clot (MCE(EXTEM)-MCE(FIBTEM)). Blood samples were collected before surgery, immediately after CPB, and after administration of FFP or FFP and platelet concentrate.
Following CPB, the endogenous thrombin potential decreased to 93%, from median 1485 (interquartile range 1207, 1777) to 1382 (1190, 1533) nM*min (P>0.05), MCE(FIBTEM) decreased to 62%, from 21 (19, 29) to 14 (12, 19) (P<0.001), and the platelet component to 73%, from 139 (119, 174) to 101 (87, 121) (P<0.001). Administration of 11 (10, 13) ml per kg of bodyweight (ml/kgbw) FFP (40 patients), or of 13 (10, 18) ml/kgbw FFP and 7 (5, 9) ml/kgbw platelet concentrate (18 patients) brought no statistically significant changes in these parameters.
Fibrin formation is more impaired than thrombin generation and the platelet component of the whole blood clot immediately after cardiopulmonary bypass.

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    • "Schols et al.[6] showed a decrease in thrombin generation associated with a decrease in fibrin formation (assessed with thromboelastography). In addition, Solomon et al[7] have shown that fibrin formation is more altered than thrombin generation following CPB. Furthermore, Coakley et al.[8] have shown a correlation between pre- and post-operative Endogenous Thrombin Potentials (ETP), and more importantly an association with bleeding complications, suggesting that this assay is informative in this context [5]. "
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    ABSTRACT: Background Bleeding remains a potentially lethal complication of cardio-pulmonary bypass (CPB) surgery. The purpose of this study was to obtain a better insight into in vitro thrombin generation in the context of CPB. Methods We used Calibrated Automated Thrombography to assess blood coagulation of 10 low-risk patients operated for valve replacement with CPB, under 2 experimental conditions, one implicating platelets as platelet dysfunction has been described to occur during CPB. Results Our main finding was that CPB-induced coagulopathy was differently appreciated depending on the presence or absence of platelets: the decrease in thrombin generation was much less pronounced in their presence (mean endogenous thrombin potential change values before and after CPB were -3.9% in the presence of platelets and -39.6% in their absence). Conclusion Our results show that experimental conditions have a profound effect in the study of in vitro thrombin generation in the context of CPB.
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    ABSTRACT: Fibrinogen is involved in both primary and secondary hemostasis, playing an important role in platelet aggregation and the establishment of a fibrin network. Recent evidence suggests that very high levels of fibrinogen act as antithrombin and can reduce endogenous thrombin potential and compromise clot stability, particularly following a low tissue factor stimulus. Several laboratory methods for measuring plasma fibrinogen concentrations are available, but results vary depending on the type of method and the use of artificial colloid plasma expanders. Adopting only the Clauss method can provide erroneously high levels when used in patients who have received colloid plasma expanders. This may contribute to a hazardous delay or complete lack of treatment. Multiple in vitro experiments, animal studies, and proof-of-principle randomized, clinical studies have recently suggested that hemostatic intervention with a fibrinogen concentrate may be efficient and safe in controling perioperative bleeding. In particular, fibrinogen concentrate has a key role in improving clotting function and reducing blood loss in settings such as trauma and cardiothoracic surgery. However, prospective studies are needed to determine the clinical efficacy and safety of fibrinogen concentrate when used as a hemostatic intervention for patients with massive bleeding due to trauma or surgery.
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    ABSTRACT: Thrombin is a key component in the coagulation cascade, and impaired thrombin generation has been linked to increased bleeding after surgical procedures. The aim was to evaluate postoperative thrombin generation capacity in plasma after cardiac surgery, and its potential associations to activity of individual coagulation factors and heparin. Forty-eight coronary artery bypass grafting patients were included in a prospective observational cohort study. Thrombin generation capacity was analysed in plasma with calibrated automated thrombogram with tissue factor as activator before (baseline), and 2h and 24h after surgery. In addition, plasma activity of coagulation factors II, V, VII, VIII, IX, X, XI, XIII, were determined. Heparin effect was assessed by anti-Xa activity, APTT and thrombin time. Thrombin generation was markedly reduced 2h after surgery compared to baseline. Peak levels decreased with median 74% (interquartile range 52-90), p<0.001, and endogenous thrombin generation potential decreased with 65% (43-86), p<0.001. Postoperative changes in endogenous thrombin generation potential correlated inversely to changes in anti-Xa activity (r=-0.51, p=0.010) and to changes in thrombin time (r=-0.51, p=0.009), but there were no correlations to changes in individual coagulation factor activity. A marked reduction in thrombin generation potential was observed in the early postoperative phase after cardiac surgery. The decrease was independent of reductions in individual coagulation factor activity but correlated to heparin effects. The results indicate that a sustained heparin effect contributes to the postoperative reduction in thrombin generation capacity.
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