In vitro effects of detergent sclerosants on antithrombotic mechanisms.
OBJECTIVE
To investigate the in vitro effects of detergent sclerosants on antithrombotic pathways.


METHODS
Proteins C, S and antithrombin (AT) were assayed in normal plasma treated with increasing concentrations of sodium tetradecyl sulphate (STS) and polidocanol (POL). Activated protein C (APC) was investigated by mixing normal plasmas with sclerosants and testing with the activated partial thromboplastin time (APTT) and dilute Russell's viper venom time in the presence and absence of APC. The effect on factor Xa (FXa), heparin and enoxaparin was investigated using chromogenic anti-FXa and APTT methods.


RESULTS
High concentration (>0.6%) STS significantly destroyed proteins C, S and AT whereas POL only caused a mild reduction in PC and AT and a moderate (60%) reduction in PS levels. STS potentiated the anticoagulant effect of APC while POL increased APC resistance. STS mimicked AT and demonstrated significant anti-Xa and anti-IIa activity. STS demonstrated a similar anticoagulant profile to heparin but was 1000x weaker. It also significantly potentiated the anticoagulant effect of heparin while POL had less effect.


CONCLUSIONS
STS and POL demonstrated quite distinct and sometimes opposite effects on the antithrombotic mechanisms assayed. These effects were concentration-dependent and in general, STS had the greatest effect on antithrombotic proteins.
Haematology Research Laboratory, St Vincent's Hospital Applied Medical Research, DARLINGHURST, 2010 Sydney, Australia. kparsi@ozemail.com.au
K
K
Parsi
T
T
Exner
J
J
Low
D Dang Fung
DD
Ma
J E
JE
Joseph
D000925:Anticoagulants / Q000494:pharmacology; D000991:Antithrombins / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D003902:Detergents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000494:pharmacology; D015951:Factor Xa / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D010314:Partial Thromboplastin Time; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D011517:Prothrombin Time; D012597:Sclerosing Solutions / Q000494:pharmacology*; D012981:Sodium Tetradecyl Sulfate / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control*
D000925:Anticoagulants; D000991:Antithrombins; D003902:Detergents; D017984:Enoxaparin; D011486:Protein C; D017293:Protein S; D012597:Sclerosing Solutions; D000077423:Polidocanol; D011092:Polyethylene Glycols; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa; D012981:Sodium Tetradecyl Sulfate