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Plasma Inhibition of the Heparin Accelerated Neutralisation of Xa by Antithrombin

I.R. MacGregor, D.A. Lane, V.V. Kakkar
1979 VIIth International Congress on Thrombosis and Haemostasis   unpublished
The ability of heparin fractions of different MW (mean MW 8500-30,000) to potentiate the action ot antithrombin III against the coagulation factors thrombin and Xa has been examined in purified reaction mixtures and in plasma. Residual thrombin and Xa have been determined by their peptidase activities against the synthetic peptide substrates H-D-Phe Pip-Arg-pNA and Bz-Ile-Glu-Gly-Arg-pNA. High MW heparin fractions were found to have higher anticoagulant activities than low MW heparin when
more » ... heparin when studied with both thrombin and Xa incubation mixtures in purified mixtures. The inhibition of thrombin by heparin fractions and antithrombin III was unaffected by other plasma components. However, normal human plasma contained a component that inhibited the heparin and antithrombin III inhibition of Xa, particularly when the high MW heparin fraction was used. Experiments using a purified preparation of platelet factor 4 suggested that this platelet derived heparin neutralising protein was not responsible for the inhibition and that a hitherto undescribed inhibitor of heparin action is present in plasma. Preliminary studies have indicated that the inhibitor is concentrated in a fraction rich in lipoprotein and obtained by ultracentrifugation of plasma in high density salt.
doi:10.1055/s-0039-1684675 fatcat:2p4rrv4rjfgytdcy2gurmbp7gu