title: The loss of homeostasis in hemostasis: new approaches in treating and understanding acute disseminated intravascular coagulation in critically ill patients.
abstract: Disseminated intravascular coagulation (DIC) profoundly increases the morbidity and mortality of patients who have sepsis. Both laboratory and clinical research advanced the understanding of the biology and pathophysiology of DIC. This, in turn, gave rise to improved therapies and patient outcomes. Beginning with a stimulus causing disruption of vascular integrity, cytokines and chemokines cause activation of systemic coagulation and inflammation. Seemingly paradoxically, the interplay between coagulation and inflammation also inhibits endogenous anticoagulants, fibrinolytics, and antiinflammatory pathways. The earliest documented and best-studied microbial cause of DIC is the lipopolysaccharide endotoxin of Gram-negative bacteria. Extensive microvascular thrombi emerge in the systemic vasculature due to dysregulation of coagulation. The result of this unrestrained, widespread small vessel thromboses multiorgan system failure. Consumption of platelets and coagulation factors during this process can lead to an elevated risk of hemorrhage. The management of these patients with simultaneous hemorrhage and thrombosis is complex and challenging. Definitive treatment of DIC, and attenuation of end-organ damage, requires control of the inciting cause. Currently, activated protein C is the only approved therapy in the United States for sepsis complicated by DIC. Further research is needed in this area to improve clinical outcomes for patients with sepsis.
authors.affiliation: Division of Hematology/Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. Karen.Hook@uphs.upenn.edu
authors.forename: Karen M
authors.initials: KM
authors.lastname: Hook
authors.forename: Charles S
authors.initials: CS
authors.lastname: Abrams
mesh_terms: D000208:Acute Disease; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001780:Blood Coagulation Tests; D016638:Critical Illness; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy; D006487:Hemostasis / Q000187:drug effects*; D006706:Homeostasis; D006801:Humans; D009102:Multiple Organ Failure / Q000097:blood / Q000188:drug therapy; D011237:Predictive Value of Tests; D011486:Protein C / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D011486:Protein C