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4G4G genotype of the plasminogen activator inhibitor‐1 promoter polymorphism associates with disseminated intravascular coagulation in children with systemic meningococcemia
Author(s) -
BINDER A.,
ENDLER G.,
MÜLLER M.,
MANNHALTER C.,
ZENZ W.
Publication year - 2007
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02724.x
Subject(s) - disseminated intravascular coagulation , medicine , sepsis , meningococcal disease , fibrinolysis , plasminogen activator inhibitor 1 , fibrinogen , genotype , gastroenterology , immunology , plasminogen activator , neisseria meningitidis , biology , gene , genetics , bacteria
Summary. 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.