Residual vein thrombosis and onset of post-thrombotic syndrome: influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene.
BACKGROUND
Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades. In this prospective cohort analytic study, we investigated the role of this single nucleotide polymorphism in the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome.


METHODS
In a group of 168 patients with post-surgical deep vein thrombosis of the legs, we analyzed the 4G/5G polymorphism in the promoter of PAI-1 gene and plasmatic PAI-1 activity. Enrolled patients were divided in two groups: patients with 4G/5G polymorphism and increased PAI-1 activity (n=85) and patients without 4G/5G polymorphism and normal PAI-1 activity (n=83). All patients were treated according to current protocols and re-examined after 3, 12 and 36 months in order to evaluate the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome.


RESULTS
We found a significantly increased PAI activity in carrier of the 4G allele, who experienced much more frequently a persistence of thrombosis after 3, 12 and 36 months and/or the development of post-thrombosis syndrome, in spite of the anticoagulant treatment.


CONCLUSIONS
These data not only confirm the role played by PAI-1 activity and by the 4G/5G SNP of the PAI-1 gene, but also suggest that current therapeutic protocols, recommending the administration of low weight molecular heparin and oral anticoagulant for the treatment of deep vein thrombosis, could be non sufficient for patients genetically predisposed to a less efficient clot lysis.
Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Via Del Vespro 127, 90129 Palermo. Electronic address: e.incalcaterra@email.it.
Egle
E
Incalcaterra
Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Via Del Vespro 127, 90129 Palermo.
Francesco
F
Meli
Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Via Del Vespro 127, 90129 Palermo.
Ida
I
Muratori
Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Via Del Vespro 127, 90129 Palermo.
Egle
E
Corrado
Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Via Del Vespro 127, 90129 Palermo.
Corrado
C
Amato
Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Via Del Vespro 127, 90129 Palermo.
Baldassare
B
Canino
Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Via Del Vespro 127, 90129 Palermo.
Filippo
F
Ferrara
D000483:Alleles; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D054070:Postthrombotic Syndrome / Q000097:blood / Q000235:genetics*; D011446:Prospective Studies; D020246:Venous Thrombosis / Q000097:blood / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human
Anticoagulant agents; Deep vein thrombosis; Fibrinolytic disorders; Genetic polymorphisms; Plasminogen activator inhibitor 1; Sigle nuclear polymorphisms