title: Tranexamic acid, an inhibitor of plasminogen activation, aggravates staphylococcal septic arthritis and sepsis.
abstract: Haemostatic balance shifts towards pro-coagulation during infection. Plasminogen, a key molecule of fibrinolysis, may play an important role in the pathogenesis of staphylococcal infections. In the present study, we assessed the impact of inhibition of plasminogen activation by tranexamic acid on the course of staphylococcal sepsis and septic arthritis in mice. We found significantly down-regulated plasmin activity and increased D-dimer levels in the blood from the mice with staphylococcal sepsis. Treatment with tranexamic acid significantly increased the severity and mortality of staphylococcal infection. In addition, tranexamic acid reduced the survival rate in a murine model for staphylococcal enterotoxin A-induced death. The aggravation of diseases by tranexamic acid was due neither to the pro-inflammatory cytokine network, nor to impairment of bacterial clearance. Modulation of fibrinolysis, either by supplement of fibrinolytic molecules (tissue plasminogen activator or plasmin) or by fibrinogen depletion, did not reduce the mortality of staphylococcal sepsis. In conclusion, we report that treatment with tranexamic acid led to distinct aggravation of staphylococcal septic arthritis and sepsis in mice, suggesting the clinical importance of fibrinolytic balance in staphylococcal infection.
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg Hospital, Göteborg, Sweden.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kłak
authors.forename: Nicola
authors.initials: N
authors.lastname: Anäkkälä
authors.forename: Wanzhong
authors.initials: W
authors.lastname: Wang
authors.forename: Stefan
authors.initials: S
authors.lastname: Lange
authors.forename: Ing-Marie
authors.initials: IM
authors.lastname: Jonsson
authors.forename: Andrej
authors.initials: A
authors.lastname: Tarkowski
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
mesh_terms: D000818:Animals; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001170:Arthritis, Infectious / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D004768:Enterotoxins / Q000633:toxicity; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D014115:Toxemia / Q000401:mortality; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000933:Antifibrinolytic Agents; D004768:Enterotoxins; C026066:enterotoxin A, Staphylococcal; D014148:Tranexamic Acid; D005341:Fibrinolysin