Interaction of fibrinolysis and prothrombotic risk factors in neonates, infants and children with and without thromboembolism and underlying cardiac disease. a prospective study.
To evaluate the role of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in children with an estimated risk of vascular occlusion reported to range from 7% to 16%, we conducted a prospective study in infants and children with underlying cardiac disease. One hundred and twenty-five children (neonate - 16 years) were investigated. In 9 infants out of the 125 children vascular occlusion occurred, closely related to cardiac catheterisation and arterial or venous lines during major cardiac surgery. Six of the nine neonates and infants with (n=6) and without (n=3) prothrombotic risk factors showed evidence of a basically impaired fibrinolytic system. Five of the nine infants showed increased PAI-1 clearly correlated to the 4G/4G genotype of the plasminogen activator-1 promoter polymorphism along with elevated t-PA concentration before the first diagnostic cardiac catheterisation was performed. One infant presented with increased t-PA concentration only. Five of the six children with reduced fibrinolytic capacity had further prothrombotic risk factors.


CONCLUSIONS
Data of this study indicate that neonates and infants with underlying cardiac disease and basically increased PAI-1 due to the 4G/4G variant of the PAI-1 promoter polymorphism along with elevated t-PA levels in combination with further prothrombotic risk factors are at high risk of developing early thromboembolism during cardiac catheterisation.
Nowak-Göttl
U
U
Pediatric Hematology and Oncology, University Hospital Münster, D-48149 Münster, Germany. leagottl@uni-muenster.de
Kotthoff
S
S
Hagemeyer
E
E
Junker
R
R
Kehl
H G
HG
Vielhaber
H
H
Kececioglu
D
D
D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D006328:Cardiac Catheterization / Q000009:adverse effects*; D016022:Case-Control Studies; D002405:Catheterization, Central Venous / Q000009:adverse effects; D002408:Catheters, Indwelling / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000235:genetics; D005342:Fibrinolysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006330:Heart Defects, Congenital / Q000097:blood* / Q000601:surgery; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017270:Lipoprotein(a) / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000502:physiology*; D011110:Polymorphism, Genetic; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D020151:Protein C Deficiency / Q000453:epidemiology / Q000235:genetics; D011516:Prothrombin / Q000235:genetics; D012307:Risk Factors; D013923:Thromboembolism / Q000453:epidemiology* / Q000209:etiology; D019851:Thrombophilia / Q000453:epidemiology* / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000502:physiology*
D020413:3' Untranslated Regions; D017270:Lipoprotein(a); D017395:Plasminogen Activator Inhibitor 1; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D010959:Tissue Plasminogen Activator