Functional Fibrinolysis Assays Reveal Different Mechanisms underlying Plasminogen Dysfunction in Ligneous Conjunctivitis.
Adolescent
Blood Coagulation Tests
Case-Control Studies
Child
Child, Preschool
Conjunctivitis
/ diagnosis
Eye
/ metabolism
Female
Fibrin
/ metabolism
Fibrinolysis
Genetic Predisposition to Disease
Heredity
Heterozygote
Homozygote
Humans
Kinetics
Male
Membrane Proteins
/ metabolism
Middle Aged
Mutation
Pedigree
Phenotype
Plasminogen
/ deficiency
Predictive Value of Tests
Skin Diseases, Genetic
/ diagnosis
Tissue Plasminogen Activator
/ metabolism
Young Adult
Journal
Thrombosis and haemostasis
ISSN: 2567-689X
Titre abrégé: Thromb Haemost
Pays: Germany
ID NLM: 7608063
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
25
8
2020
Statut:
ppublish
Résumé
Ligneous conjunctivitis (LC) is a rare disorder associated with plasminogen deficiency characterized by chronic fibrin deposits in the eyelids. All patients with plasminogen deficiency do not develop LC, whose underlying mechanisms remain unknown. We investigated whether fibrinolytic activity was correlated with phenotype and/or genotype in patients suffering from LC and their relatives. Plasminogen activity/antigen levels and Plasminogen activity varied from <10 to 40% in patients, 36 to 105% in relatives, and >80% in control healthy individuals. Homozygous K19E mutation was associated with normal antigenic plasminogen levels. In front-lysis experiments, all patients had a lower fibrinolysis rate as compared with their relatives and to control individuals. The cell-based ECLT and plasminogen activation assay demonstrated that urokinase-mediated fibrinolysis was not impaired in patients with homozygous K19E mutation compared with the other mutants. We confirm that plasminogen levels fail to predict LC occurrence. In these conditions, t-PA clot lysis front is useful to predict clinical outcome in plasminogen deficiency. Moreover, we provide evidence that occurrence of LC overlaps quantitative and qualitative plasminogen deficiencies. The homozygous K19E mutation is associated with isolated impaired t-PA-mediated fibrinolysis compared with other mutants.
Sections du résumé
BACKGROUND
BACKGROUND
Ligneous conjunctivitis (LC) is a rare disorder associated with plasminogen deficiency characterized by chronic fibrin deposits in the eyelids. All patients with plasminogen deficiency do not develop LC, whose underlying mechanisms remain unknown.
OBJECTIVE
OBJECTIVE
We investigated whether fibrinolytic activity was correlated with phenotype and/or genotype in patients suffering from LC and their relatives.
METHODS
METHODS
Plasminogen activity/antigen levels and
RESULTS
RESULTS
Plasminogen activity varied from <10 to 40% in patients, 36 to 105% in relatives, and >80% in control healthy individuals. Homozygous K19E mutation was associated with normal antigenic plasminogen levels. In front-lysis experiments, all patients had a lower fibrinolysis rate as compared with their relatives and to control individuals. The cell-based ECLT and plasminogen activation assay demonstrated that urokinase-mediated fibrinolysis was not impaired in patients with homozygous K19E mutation compared with the other mutants.
CONCLUSION
CONCLUSIONS
We confirm that plasminogen levels fail to predict LC occurrence. In these conditions, t-PA clot lysis front is useful to predict clinical outcome in plasminogen deficiency. Moreover, we provide evidence that occurrence of LC overlaps quantitative and qualitative plasminogen deficiencies. The homozygous K19E mutation is associated with isolated impaired t-PA-mediated fibrinolysis compared with other mutants.
Identifiants
pubmed: 32369847
doi: 10.1055/s-0040-1709526
doi:
Substances chimiques
Membrane Proteins
0
PLAU protein, human
0
Fibrin
9001-31-4
Plasminogen
9001-91-6
Tissue Plasminogen Activator
EC 3.4.21.68
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
758-767Informations de copyright
Georg Thieme Verlag KG Stuttgart · New York.
Déclaration de conflit d'intérêts
None declared.