Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease.
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.
Brandtzaeg
P
P
Department of Infectious Diseases, Ullevål University Hospital, Oslo, Norway.
Joø
G B
GB
Brusletto
B
B
Kierulf
P
P
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*
D004731:Endotoxins; D005338:Fibrin Fibrinogen Degradation Products; D015849:Plasminogen Inactivators; D000979:alpha-2-Antiplasmin; D010958:Plasminogen