Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease

Thromb Res. 1990 Jan 15;57(2):271-8. doi: 10.1016/0049-3848(90)90326-8.

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.

MeSH terms

  • Disseminated Intravascular Coagulation / blood
  • Disseminated Intravascular Coagulation / complications
  • Endotoxins / blood*
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Humans
  • Meningococcal Infections / blood*
  • Meningococcal Infections / complications
  • Plasminogen / metabolism*
  • Plasminogen Inactivators / blood*
  • Platelet Count
  • Sepsis / blood
  • Sepsis / complications
  • alpha-2-Antiplasmin / metabolism*

Substances

  • Endotoxins
  • Fibrin Fibrinogen Degradation Products
  • Plasminogen Inactivators
  • alpha-2-Antiplasmin
  • Plasminogen