PLASMINOGEN-ACTIVATOR INHIBITOR-1 AND INHIBITOR-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 (>700 ng/L) levels of endotoxin (LPS) in plasma and severe coagulopathy, had significantly lower functional levels of plasminogen (P< 0.05) and alpha-2-antiplasmin (P > 0.01) and higher antigen levels of plasminogen activator inhibitor 1 (PAI-1) (P <0.01), and fibrin degradation products (FDP) (P< 0.01), but not of PAI-2 (P >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 <0.0001). Decreasing admission levels of platelets were associated with increasing levels of PAI-1 (r=-0.55, P<0.001). After initiation of treatment with antibiotics and fresh frozen plasma, the PAI-1 levels declined rapidly. PAI-1 levels >360 ug/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 >260 ug/L. PAI-1 levels >1850 ug/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. © 1990.