Document Detail


Thrombin-activatable fibrinolysis inhibitor is associated with severity and outcome of severe meningococcal infection in children.
MedLine Citation:
PMID:  18021301     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVES: In pediatric meningococcal sepsis, an imbalance between coagulation and fibrinolysis and proinflammatory action play major roles. We hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and/or TAFI activation markers are involved in the pathogenesis of meningococcal sepsis. PATIENTS AND METHODS: Children with severe meningococcal sepsis (n = 112) previously included in Rotterdam-based trials participated in this study. Clinical and laboratory parameters and severity scores were assessed. TAFI and TAFI activation markers were determined: TAFI activation peptide (TAFI-AP) and (in)activated TAFI [TAFIa(i)]. The -438G/A, Ala147Thr, and Thr325Ile polymorphisms were genotyped. RESULTS: TAFI levels were significantly decreased in patients with meningococcal disease at admission compared to the convalescence state. TAFI was decreased in patients with septic shock vs. those with no shock. TAFI-AP levels were increased in patients with disseminated intravascular coagulation (DIC) vs. patients without DIC. TAFI-AP and TAFIa(i) were significantly increased in non-survivors vs. survivors. TAFI-AP levels and the TAFI-AP/TAFI ratio were also strongly correlated to severity scores and laboratory parameters. The TAFI 325Ile/Ile genotype was overrepresented in patients with DIC. CONCLUSIONS: Activation markers of TAFI were associated with the occurrence of DIC and mortality in meningococcal sepsis patients. A determination of TAFI, TAFI-AP, and TAFIa(i) is required to enable coherent interpretation of the role of TAFI in disease.
Authors:
M Emonts; E L E de Bruijne; A H C Guimarães; P J Declerck; F W G Leebeek; M P M de Maat; D C Rijken; J A Hazelzet; A Gils
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-11-15
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  6     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-24     Completed Date:  2008-05-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  268-76     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Carboxypeptidase U / blood*,  genetics
Child
Child, Preschool
Disseminated Intravascular Coagulation / blood,  epidemiology,  etiology
Enzyme Activation
Female
Genetic Predisposition to Disease
Genotype
Humans
Infant
Male
Meningococcal Infections / blood*,  complications,  microbiology,  mortality
Mutation, Missense
Neisseria meningitidis / classification,  isolation & purification
Point Mutation
Serotyping
Severity of Illness Index
Shock, Septic / blood,  epidemiology,  etiology
Survival Analysis
Treatment Outcome
Chemical
Reg. No./Substance:
EC 3.4.17.20/Carboxypeptidase U

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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