The implementation of metalloproteinases and their inhibitors as new biomarkers for the severity of sepsis and for mortality in critically ill patients may provide promising decision support Abiraterone for the intensivist to guide the allocation of hospital resources. Additional larger studies are needed, however, to determine the cellular origin and the relevance of these enzymes in sepsis.AbbreviationsIL: interleukin; MMP: matrix metalloproteinase; TIMP: tissue inhibitor of matrix metalloproteinase; TNF: tumor necrosis factor.Competing interestsMBr is an employee of Boehringer Ingelheim GmbH, Germany. The other authors declare that they have no competing interests.NotesSee related research by Lorente et al., http://ccforum.com/content/13/5/R158, and related letter by Lorente et al., http://ccforum.
com/content/14/1/402AcknowledgementsThe present work was supported by a grant of the Faculty of Medicine Mannheim, University of Heidelberg, Germany.
An increasing number of people in economically developed nations are receiving oral anticoagulants for the treatment and prophylaxis of thromboembolic diseases [1,2]. Among the most commonly used oral anticoagulants are the synthetic coumarin derivatives warfarin, acenocoumarol and phenprocoumon. All three drugs act by inhibiting the biosynthesis of the vitamin K-dependent clotting factors (factors II, VII, IX and X), which produces a functional deficit of these procoagulant proteins [2].
The main indications for vitamin K antagonists are: primary and secondary prevention of venous thromboembolism; prevention of systemic embolism (for example, stroke) in patients with mechanical heart valves or atrial fibrillation; and prophylaxis (as adjunctive therapy) for systemic embolism following myocardial infarction [3].While the antithrombotic benefits of oral anticoagulants are well established, these therapies increase the risk of hemorrhagic events, some of which may be severe or even life-threatening [4-7]. The risk of bleeding in patients receiving anticoagulants increases with surgery, trauma, over-anticoagulation or raised international normalized ratios (INRs) – although complications can still occur when the INR is within the therapeutic range [1,2,4,5,8-10].Because of the association between vitamin K antagonists and an increased risk of hemorrhagic events, patients undergoing emergency procedures and those with life-threatening/major bleeding or highly elevated INRs require urgent and immediate reversal of anticoagulant activity [1,5,11].
Recommended treatments for rapid reversal of oral anticoagulant therapy include fresh frozen plasma (FFP) and prothrombin complex concentrates (PCCs); in all cases these should be supplemented with oral or intravenous vitamin K [1,3,5,11-17]. PCCs, which contain three or four vitamin K-dependent clotting factors, offer a number of advantages AV-951 over FFP.