title: Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease.
abstract: We have studied the activation state of the fibrinolytic system in 39 patients with systemic meningococcal disease (SMD). Patients defined as having fulminant septicemia (n = 13) with high (greater than 700 ng/L) levels of endotoxin (LPS) in plasma and severe coagulopathy, had significantly lower functional levels of plasminogen (P less than 0.05) and alpha-2-antiplasmin (P less than 0.01) and higher antigen levels of plasminogen activator inhibitor 1 (PAI-1) (P less than 0.01), and fibrin degradation products (FDP) (P less than 0.01), but not of PAI-2 (P greater than 0.1) as compared with less severely ill patients (meningitis and meningococcemia) (n = 25). A positive correlation existed between the admission (maximum) levels of LPS and PAI-1 (r = 0.86, P less than 0.0001). Decreasing admission levels of platelets were associated with increasing levels of PAI-1 (r = -0.55, P less than 0.001). After initiation of treatment with antibiotics and fresh frozen plasma, the PAI-1 levels declined rapidly. PAI-1 levels greater than 360 micrograms/L on admission predicted the development of a severe septic shock combined with renal impairment correctly in 12 of 13 patients (92%). None of 25 patients without multiple organ failure had PAI-1 levels greater than 260 micrograms/L. PAI-1 levels greater than 1850 micrograms/L were associated with 100% fatality. The results suggest that in the early phase of fulminant meningococcal septicemia an extensive plasmin generation occurs. On admission, however, high levels of PAI-1 seem to inhibit the plasmin generation, and thereby promote DIC.
authors.affiliation: Department of Infectious Diseases, Ullevål University Hospital, Oslo, Norway.
authors.forename: P
authors.initials: P
authors.lastname: Brandtzaeg
authors.forename: G B
authors.initials: GB
authors.lastname: Joø
authors.forename: B
authors.initials: B
authors.lastname: Brusletto
authors.forename: P
authors.initials: P
authors.lastname: Kierulf
mesh_terms: D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000150:complications; D004731:Endotoxins / Q000097:blood*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D008589:Meningococcal Infections / Q000097:blood* / Q000150:complications; D010958:Plasminogen / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000097:blood*; D010976:Platelet Count; D018805:Sepsis / Q000097:blood / Q000150:complications; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D005338:Fibrin Fibrinogen Degradation Products; D015849:Plasminogen Inactivators; D000979:alpha-2-Antiplasmin; D010958:Plasminogen