Disseminated intravascular coagulation is provoked by several underlying disorders (sepsis, cancer, trauma, and pregnancy complicated with eclampsia or other calamities). Treatment of the underlying disease and elimination of the trigger mechanism are the cornerstone therapeutic approaches. Therapeutic strategies specific for DIC aim to control activation of blood coagulation and bleeding risk. The clinical trials using DIC as entry criterion are limited. Large randomized, phase III clinical trials have investigated the efficacy of antithrombin (AT), activated protein C (APC), tissue factor pathway inhibitor (TFPI), and thrombomodulin (TM) in patients with sepsis, but the diagnosis of DIC was not part of the inclusion criteria. Treatment with APC reduced 28-day mortality of patients with severe sepsis, including patients retrospectively assigned to a subgroup with sepsis-associated DIC. Treatment with APC did not have any positive effects in other patient groups. The APC treatment increased the bleeding risk in patients with sepsis, which led to the withdrawal of this drug from the market. Treatment with AT failed to reduce 28-day mortality in patients with severe sepsis, but a retrospective subgroup analysis suggested possible efficacy in patients with DIC. Clinical studies with recombinant TFPI or TM have been carried out showing promising results. The efficacy and safety of other anticoagulants (ie, unfractionated heparin, low-molecular-weight heparin) or transfusion of platelet concentrates or clotting factor concentrates have not been objectively assessed. Keywords disseminated intravascular coagulation, sepsis, antithrombin, activated protein C, thrombomodulin, tissue factor pathway inhibitor 1 Service Anesthe´sie, Re´animation Hoˆpital Tenon, Hoˆpitaux Universitaires Est Parisien, Assistance Publique Hoˆpitaux de Paris, Paris, France 2 INSERM UMRS1140, Universite´ Paris Descartes, Paris, France 3 Service d’He´matologie Biologique, Hoˆpital Cochin, Assistance Publique des Hoˆpitaux de Paris, France 4 De´partement d’He´matologie, Faculte´ de Pharmacie, Universite´ Fe´lix Houphoue¨t Boigny, Abidjan, Coˆte d’Ivoire 5 Department of Pathology, Cardiovascular Institute Loyola University Chicago, Maywood, IL, USA 6 Service d’He´matologie Biologique Hoˆpital Tenon, Hoˆpitaux Universitaires Est Parisien, Assistance Publique Hooˆpitaux de Paris, Paris, France 7 Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Institut National de la Sante´ et de la Recherche Me´dicale, INSERM U938 and Faculte´ de Me´decine Pierre et Marie Curie (UPMC), Sorbonne Universities, Paris, France Corresponding Author: Grigoris T. Gerotziafas, Service d’He´matologie Biologique Hoˆpital Tenon, Hoˆpitaux Universitaires Est Parisien, Assistance Publique Hoˆpitaux de Paris, 4 rue de la Chine, 75020 Paris, Cedex 20, France. Email: grigorios.gerotziafas@aphp.fr Clinical and Applied Thrombosis/Hemostasis 2018, Vol. 24(9S) 8S-28S ª The Author(s) 2018 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1076029618806424 journals.sagepub.com/home/cat Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons AttributionNonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). Introduction Disseminated intravascular coagulation (DIC) is a lifethreatening syndrome characterized by disseminated and often uncontrolled activation of coagulation. This syndrome is associated with a high risk of macro- and microvascular thrombosis and progressive consumption coagulopathy, which leads to an increased bleeding risk. Several pathological conditions may trigger DIC (Table 1), with sepsis, cancer, trauma, and obstetric calamity ranking among the most frequent triggering factors.1 The risk of DIC is particularly high in patients with sepsis. Indeed, DIC occurs in 30% to 50% of them, whereas the frequency of DIC is