Anticoagulant activities of pentosan polysulphate (Hémoclar) due to release of hepatic triglyceride lipase (HTGL)

Barrowcliffe, T.W.; Gray, E.; Merton, R.E.; Dawes, J.; Jennings, C.A.; Hubbard, A.R.; Thomas, D.P.

Thrombosis and Haemostasis 56(2): 202-206

1986


ISSN/ISBN: 0340-6245
PMID: 2433786
Document Number: 3793
Subcutaneous injections of 50 mg pentosan polysulphate (Hémoclar) were given to normal volunteers and the effects on anti-Factor Xa activity, thrombin generation and lipase release measured. Concentrations of pentosan polysulphate were measured by a competitive binding assay and the mean peak level found to be 1.6 micrograms/ml. Anti-Xa clotting activity rose to 0.034 iu/ml and thrombin generation induced by lipid peroxides was inhibited by approximately 50%. Neither of these effects could be accounted for by the direct action of pentosan polysulphate at the concentrations measured. Pentosan polysulphate was very effective in releasing lipase, approximately 70-80% of the total enzyme activity being due to hepatic triglyceride lipase (HTGL). In vitro addition of purified HTGL to plasma markedly enhanced anti-Xa clotting activity, and caused a 70% inhibition of lipid peroxide induced thrombin generation. Anti-Xa activity of post-injection plasma was increased rather than neutralised by addition of polybrene, and this effect could be mimicked by addition of polybrene to plasma containing pentosan polysulphate and purified HTGL. It is concluded that, when given in low doses subcutaneously, pentosan polysulphate acts as an indirect anticoagulant, its major effects being due to release of HTGL.

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Anticoagulant activities of pentosan polysulphate (Hémoclar) due to release of hepatic triglyceride lipase (HTGL)