In vitro effects of detergent sclerosants on fibrinolytic enzymes and inhibitors.
OBJECTIVE
To investigate the effects of Sodium Tetradecyl Sulphate (STS) and Polidocanol (POL) on fibrinolytic mechanisms.


METHODS
Measurements were done with serial dilutions of sclerosants in whole blood (WB), platelet rich (PRP) and platelet poor plasma (PPP). Control experiments were done in 5% bovine serum albumin (BSA), spiked with the enzyme/inhibitor. Plasminogen was measured with a chromogenic assay. Alpha-2-antiplasmin (AP) activity, plasmin-alpha-2-antiplasmin (PAP) complexes, plasminogen activator inhibitor-1 (PAI-1) activity, tissue plasminogen activator (t-PA) total antigen, t-PA activity, t-PA/PAI-1 complexes, thrombin activatable fibrinolysis inhibitor (TAFI) antigen and activated TAFI (TAFIa) were measured by ELISA.


RESULTS
At high concentrations (>0.3%), STS destroyed plasminogen, PAI-1, t-PA/PAI-1 complexes and total t-PA antigen but increased t-PA activity. At low concentrations (<0.3%), both agents reduced PAP complexes while increasing AP activity. Low concentration STS increased PAI-1 activity, t-PA/PAI-1 complexes, TAFI and TAFIa. Low concentration POL mildly increased the total t-PA antigen and TAFI.


CONCLUSIONS
At low concentrations, both agents demonstrated a prothrombotic, antifibrinolytic (increase in PAI-1, total t-PA antigen, AP, TAFI and TAFIa) activity. At high concentrations, STS demonstrated non-prothrombotic (destruction of PAI-1, t-PA/PAI-1 complexes), antifibrinolytic (destruction of plasminogen, increase in AP) activity while POL had minimal effect.
Parsi
Kurosh
K
Haematology Research Laboratory, St Vincent's Hospital, Sydney, Australia. kparsi@ozemail.com.au
Exner
Thomas
T
Ma
David Dang Fung
DD
Joseph
Joanne Emily
JE
D025901:Carboxypeptidase B2 / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000494:pharmacology*; D012597:Sclerosing Solutions / Q000494:pharmacology*; D012981:Sodium Tetradecyl Sulfate / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D003902:Detergents; D017395:Plasminogen Activator Inhibitor 1; D012597:Sclerosing Solutions; D000979:alpha-2-Antiplasmin; D000077423:Polidocanol; D011092:Polyethylene Glycols; D010958:Plasminogen; D025901:Carboxypeptidase B2; D010959:Tissue Plasminogen Activator; D012981:Sodium Tetradecyl Sulfate