title: Thrombin as a multi-functional enzyme. Focus on in vitro and in vivo effects.
abstract: Thrombin is the central protease in the coagulation cascade and one of the most extensively studied of all enzymes. In addition to its recognised role in the coagulation cascade and haemostasis, thrombin is known to have multiple pleiotropic effects, which mostly have been shown only in  in vitro  studies: it plays a role in inflammation and cellular proliferation and displays a mitogen activity on smooth muscle cells and endothelial cells, predominantly by activation of angiogenesis.  In vivo , thrombin effects were examined in animal models of intravenous or intraarterial thrombin infusion. An extensive literature search regarding  in vivo  data showed that i) thrombin administered as a bolus causes microembolism, ii) thrombin infused slowly at steady-state conditions (up to 1.6 U/kg/min) leads to bleeds but not to intravascular clotting, iii) large quantity of thrombin infused at low rates (0.05 U/kg/min) does not have any measurable effect, and iv) thrombin increases vascular permeability leading to tissue damage. Although several decades of research on thrombin functions have provided a framework for understanding the biology of thrombin, animal and human studies with use of newer laboratory techniques are still needed to confirm the pleiotropic thrombin functions shown in  in vitro  studies.
authors: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. jolanta.siller-matula@meduniwien.ac.at
authors: Jolanta M
authors: JM
authors: Siller-Matula
authors: Michael
authors: M
authors: Schwameis
authors: Andrew
authors: A
authors: Blann
authors: Christine
authors: C
authors: Mannhalter
authors: Bernd
authors: B
authors: Jilma
mesh_terms: D043925:Angiogenesis Inducing Agents; D000818:Animals; D001777:Blood Coagulation; D002199:Capillary Permeability; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D013917:Thrombin / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D013917:Thrombin