Author(s): Scherer RU
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Abstract Recent studies in humans have shown that tissue factor on the surface of endothelial cells, monocytes, or subendothelial structures sparks plasmatic coagulation. In vivo, there is no functional separation of an "endogenous" and "exogenous" pathway of the coagulation cascade. However, global laboratory tests run along such pathways due to preincubation with specific activators and, hence, allow localization of inherited coagulation defects. Coagulation inhibitors such as antithrombin or activated protein C are accelerated in their activity by cell surface glycoproteins and almost completely inactivate procoagulant activity in the microcirculation. Antithrombin binds to endothelial glycosaminoglycans and then significantly increases anticoagulant activity. Protein C is activated by the thrombin-thrombomodulin-complex and inactivates factors V a and VIII a, respectively. Additionally, activated protein C has a profibrinolytic effect. Both systems physiologically counteract the procoagulant transformation of endothelial and monocyte cell surfaces which occurs in critically ill patients due to induction of tissue factor, suppression of thrombomodulin, and removal of glycosaminoglycans from the cell surface. The distinction of static and dynamic coagulation disorders is useful since static disorders seldom require therapeutic interventions although global laboratory tests may continuously deteriorate. Dynamical disorders are symptoms of an underlying disease, and consumption coagulopathy with disseminated fibrin deposition and oozing occurs when coagulation turnover cannot be stopped. Antithrombin substitution is a well documented therapeutic option along with fresh frozen plasma and erythrocyte concentrate transfusion for blood substitution. Recent case reports in patients with irreversible bleeding complications favour the application of a recombinant factor VII concentrate. A rising perspective to decrease the use of heterologous blood and blood products may be intraoperative plasma retransfusion. The quality of such plasma undergoing consecutive filtration steps has to be clinically studied. The application of a synthetic platelet substitute, the "plateletsome", containing platelet glycoproteins led to significantly improved haemostasis without generating systemic procoagulant activity. In a far future, procoagulant cell surface transformation may be influenced by topic application of inhaled thrombomodulin loaded liposomes or by sense or antisense oligonucleotides inducing thrombomodulin expression or suppressing tissue factor expression, respectively.
This article was published in Zentralbl Chir
and referenced in Brain Disorders & Therapy