title: Coagulation abnormalities in sepsis.
abstract: Although the pathophysiology of sepsis has been elucidated with the passage of time, sepsis may be regarded as an uncontrolled inflammatory and procoagulant response to infection. The hemostatic changes in sepsis range from subclinical activation of blood coagulation to acute disseminated intravascular coagulation (DIC). DIC is characterized by widespread microvascular thrombosis, which contributes to multiple organ dysfunction/failure, and subsequent consumption of platelets and coagulation factors, eventually causing bleeding manifestations. The diagnosis of DIC can be made using routinely available laboratory tests, scoring algorithms, and thromboelastography. In this cascade of events, the inhibition of coagulation activation and platelet function is conjectured as a useful tool for attenuating inflammatory response and improving outcomes in sepsis. A number of clinical trials of anticoagulants were performed, but none of them have been recognized as a standard therapy because recombinant activated protein C was withdrawn from the market owing to its insufficient efficacy in a randomized controlled trial. However, these subgroup analyses of activated protein C, antithrombin, and thrombomodulin trials show that overt coagulation activation is strongly associated with the best therapeutic effect of the inhibitor. In addition, antiplatelet drugs, including acetylsalicylic acid, P2Y12 inhibitors, and glycoprotein IIb/IIIa antagonists, may reduce organ failure and mortality in the experimental model of sepsis without a concomitant increased bleeding risk, which should be supported by solid clinical data. For a state-of-the-art treatment of sepsis, the efficacy of anticoagulant and antiplatelet agents needs to be proved in further large-scale prospective, interventional, randomized validation trials.
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Anesthesiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address: cm.cmtsao@gmail.com.
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Tsao
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Anesthesiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shung-Tai
authors.initials: ST
authors.lastname: Ho
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan; Department of Pharmacology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Wu
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000188:drug therapy*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors
keywords: coagulation; disseminated intravascular coagulation (DIC); organ dysfunction; platelet; sepsis