4G4G genotype of the plasminogen activator inhibitor-1 promoter polymorphism associates with disseminated intravascular coagulation in children with systemic meningococcemia

J Thromb Haemost. 2007 Oct;5(10):2049-54. doi: 10.1111/j.1538-7836.2007.02724.x. Epub 2007 Aug 3.


Background: Meningococcal disease may present as sepsis, meningitis or a combination of both. Impaired fibrinolysis and massive elevation of the plasminogen activator inhibitor-1 (PAI-1) is a characteristic feature of meningococcal sepsis. We and others have reported an association between mortality and the functional 4G/5G promoter polymorphism of the PAI-1 gene in children with meningococcal sepsis.

Objective: Multicenter study to investigate the association of the 4G/5G PAI-1 polymorphism and disseminated intravascular coagulation (DIC) in children with meningococcal disease in a Central European population.

Patients/methods: Blood samples and clinical information of 326 previously healthy children with meningococcal infection were collected from 95 pediatric hospitals in Germany, Switzerland, Italy, and Austria from 2000 to 2002.

Results: DIC, defined as platelet counts below 100 G L(-1), increased D-dimer levels and prolonged prothrombin time, was significantly associated with the 4G4G genotype [31 of 63 (49%) vs. 55 of 175 (31%), P = 0.014], resulting in a hazard ratio (HR) of 1.5 (95% confidence interval 1.1-2.1) to develop DIC. Carriers of the 4G4G genotype showed significantly lower platelet counts (183 G L(-1) vs. 227 G L(-1), P = 0.009) on admission. Fibrinogen and C-reactive protein levels were not associated with the PAI-1 4G/5G polymorphism, nor were white blood cell counts.

Conclusions: Our data show a correlation between the 4G4G genotype of the PAI-1 gene and development of DIC in meningococcal infection.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • C-Reactive Protein / metabolism
  • Child
  • Child, Preschool
  • Disseminated Intravascular Coagulation / blood*
  • Disseminated Intravascular Coagulation / complications
  • Disseminated Intravascular Coagulation / genetics*
  • Female
  • Fibrinogen / genetics
  • Fibrinogen / metabolism
  • Genotype*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Meningococcal Infections / complications
  • Meningococcal Infections / genetics*
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*


  • Plasminogen Activator Inhibitor 1
  • Fibrinogen
  • C-Reactive Protein