Surgical Endoscopy
Original articles Surg Endosc (1992) 6 : 4 - 9
© Springer-Verlag New York Inc. 1992
Mechanism of thrombosis caused by sclerotherapy of esophageal varices using sodium tetradecyl sulphate B.F. Jacobson 1, R.C. Franz 4, E.M. Hurly l, G.L. Norman 1, P. Becket 3, J.A. Myburgh:, and B.V. Mendelow I Department of Haematology, School of Pathology of the University of the Witwatersrand Medical School and the South African Institute for Medical Research; 2 Department of Surgery, University of the Witwatersrand Medical School; 3 Institute for Biostatistics of the South African Medical Research Council, York Road, Parktown 2193, South Africa; 4 Department of Surgery, University of Pretoria, P.O. Box 667, Pretoria 0001, South Afi'ica
Summary. The mechanism of thrombosis following intravariceal injection of sodium tetradecyl sulphate (S.T.D.) was investigated with respect to effects on the vascular endothelium, the coagulation cascade, and platelet function. Using an umbilical cord model designed to simulate blood flow over the endothelium, it was found that S.T.D. is a potent toxin for endothelial cells in that brief exposure to even low concentrations of the agent were effective in stripping endothelium over a considerable distance, exposing highly thrombogenic endothelium in the process. Effects on coagulation and platelet function were found to be dependent on concentration. Diluted S.T.D. induced a hypercoagulable state, possibly in consequence of a selective inhibition of the physiological anticoagulant, protein C, and promoted platelet aggregation. Higher concentrations inactivated the coagulation cascade and lysed platelets completely. These results suggest that intravariceal infusion of S.T.D. at considerable dilution may be at least as effective in inducing thrombosis as standard dosage, and possibly more so.
Key words: Sclerotherapy - Thrombosis - Endothelium - Coagulation
Sclerotherapy of esophageal varices was first described 50 years ago [3]. It is currently being used not only for actively bleeding varices or varices which have bled [14], but also more recently as a prophylactic measure for patients who have not yet bled [12]. Controversy exists in the literature as to its exact mechanism of action, and particularly as to how, in the acute stage, it causes thrombosis. Some authors have
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claimed that the inflammatory response is the mechanism while others have shown that hypercoagulable states may be induced [7, 10]. Undoubtedly variation occurs depending on which agent is used and whether it is administered by intravariceal or paravariceal injection. In the present study we have investigated the impact of various concentrations of sodium tetradecyl sulphate (S.T.D.) on vascular endothelium, on the coagulation cascade, and on platelet function. These studies were carried out in an attempt to rationalize the dosage of S.T.D. by intravariceal injection.
Materials and methods
Coagulation profile Whole fresh citrated blood was obtained from healthy volunteers. The following parameters were evaluated as baseline levels and after addition of between 10 txl and 350 txl of S.T.D.: prothrombin time (s); partial thromboplastin time (PTT) (s); thrombin time; fibrinogen; factors II, V, VII, VIII, IX, X, XI, and XII, and protein C (using kits supplied by Boehringer Diagnostics). Statistical analysis was performed with the appropriate analysis of variance at the 0.05 level of significance with the help of Tukey's Studentized Range [8].
Thromboelastography (TEG) The thromboelastogram was used to evaluate whole blood coagulation after addition of 10 txl to 100/xl of S.T.D.
Platelet aggregation Platelet aggregometry was performed after addition of between 10/xl and 150/xl of S.T.D. to platelets from healthy volunteers. The platelets were also tested with routine agonists. Time-sequence phasecontrast light microscopy was also performed with addition of 100/zl S.T.D. to a counting chamber containing platelets.
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