Thrombin generation and bleeding in cardiac surgery: a clinical narrative review.

This narrative review discusses the role of thrombin generation in coagulation and bleeding in cardiac surgery, the laboratory methods for clinical detection of impaired thrombin generation, and the available hemostatic interventions that can be used to improve thrombin generation. Coagulopathy after cardiopulmonary bypass (CPB) is associated with excessive blood loss and adverse patient outcomes. Thrombin plays a crucial role in primary hemostasis, and impaired thrombin generation can be an important cause of post-CPB coagulopathy. Existing coagulation assays have significant limitations in assessing thrombin generation, but whole-blood assays designed to measure thrombin generation at the bed-side are under development. Until then, clinicians may need to institute therapy empirically for non-surgical bleeding in the setting of normal coagulation measures. Available therapies for impaired thrombin generation include administration of plasma, prothrombin complex concentrate, and bypassing agents (recombinant activated factor VII and factor eight inhibitor bypassing activity). In vitro experiments have explored the relative potency of these therapies, but clinical studies are lacking. The potential incorporation of thrombin generation assays into clinical practice and treatment algorithms for impaired thrombin generation must await further clinical development.

RéSUMé: Ce compte rendu narratif discute du rôle de la génération de thrombine dans la coagulation et le saignement en chirurgie cardiaque, des méthodes de laboratoire pour le dépistage clinique d'une génération de thrombine altérée et des interventions hémostatiques disponibles qui peuvent être utilisées pour améliorer la génération de thrombine. Une coagulopathie après la circulation extracorporelle (CEC) est associée à des pertes de sang excessives et à des complications pour les patients. La thrombine joue un rôle essentiel d'hémostase primaire, et une génération de thrombine altérée peut constituer une cause importante de coagulopathie post-CEC. Les analyses de coagulation existantes comportent d'importantes limites en ce qui touche à l'évaluation de la génération de thrombine, mais des analyses de sang complet conçues pour mesurer la génération de thrombine au chevet sont en cours d'élaboration. En attendant, les cliniciens pourraient devoir amorcer un traitement de manière empirique pour prendre en charge les saignements non chirurgicaux dans un contexte de valeurs de coagulation mesurées normales. Les traitements disponibles pour une génération de thrombine altérée comprennent l'administration de plasma, de concentrés de complexe prothrombinique, et d'agents de contournement (bypass) (facteur VII recombinant activé et activité de contournement de l'inhibiteur du facteur VIII). Des expériences in vitro ont exploré l'activité thérapeutique relative de ces traitements, mais les études cliniques manquent. L'intégration potentielle d'analyses de génération de thrombine dans la pratique clinique et d'algorithmes de traitement pour une génération de thrombine altérée doit attendre des développements cliniques plus poussés.

Transcatheter Aortic Valve Implantation versus Surgical Aortic Valve Replacement: Meta-Analysis of Clinical Outcomes and Cost-Effectiveness.

OBJECTIVE: Transcatheter aortic valve implantation (TAVI) has emerged as a feasible alternative treatment to conventional surgical aortic valve replacement (AVR) for high-risk patients with aortic stenosis. The present systematic review aimed to assess the comparative clinical and cost-effectiveness outcomes of TAVI versus AVR, and meta-analyse standardized clinical endpoints. METHODS: An electronic search was conducted on 9 online databases to identify all relevant studies. Eligible studies had to report on either periprocedural mortality or incremental cost-effectiveness ratio (ICER) to be included for analysis. RESULTS: The systematic review identified 24 studies that reported on comparative clinical outcomes, including three randomized controlled trials and ten matched observational studies involving 7906 patients. Meta-analysis demonstrated no significant differences in regards to mortality, stroke, myocardial infarction or acute renal failure. Patients who underwent TAVI were more likely to experience major vascular complications or arrhythmias requiring permanent pacemaker insertion. Patients who underwent AVR were more likely to experience major bleeding. Eleven analyses from 7 economic studies reported on ICER. Six analyses defined TAVI to be low value, 2 analyses defined TAVI to be intermediate value, and three analyses defined TAVI to be high value. CONCLUSION: The present study demonstrated no significant differences in regards to mortality or stroke between the two therapeutic procedures. However, the cost-effectiveness and long-term efficacy of TAVI may require further investigation. Technological improvement and increased experience may broaden the clinical indication for TAVI for low-intermediate risk patients in the future.