Comparative Turn-Over of Heparin Cofactor II and Antithrombin III in Baboons Influence of Heparin and Pentosan Polysulfate Administration

Summary

Heparin and pentosan polysulfate (PPS) interact in plasma with antithrombin III (AT III) and Heparin cofactor II (HC II) respectively. To assess the influence of heparin or PPS treatment on the metabolism of their respective cofactors, we performed a double tracer study in baboons receiving heparin or PPS. Purified AT III and HC II from human plasma were labelled with 131I and 125I respectively by the lactoperoxidase-glucose oxidase technique. The tracers had unchanged biological activities, were homogenous in SDS-PAGE, migrated as native proteins by crossed immunoelectrophoresis in the presence of heparin or PPS and virtually coeluted with endogenous baboon proteins from heparin-agarose. Nine animals were randomly allocated to receive, during the metabolic study, heparin (500 IU/kg/d, n = 3), PPS (5 mg/kg,d, n = 3) or a placebo (n = 3) given in 2 daily subcutaneous injections. Heparin levels and anticoagulant effects were similar in extent and duration to those usually achieved in man. The plasma concentrations of AT III and HC II did not vary under treatment. The half-life of the elimination phase in the placebo group ranged from 1.95 to 2.33 d for AT III and from 1.96 to 2.21 d for HC II. There was no significant difference in the half-lives of the 2 inhibitors between the placebo group and the animals receiving heparin or PPS. This suggests that clinical conditions associated with heparin treatment may be important for the effect of heparin on AT III metabolism previously reported in patients. When the data of the nine animals were pooled, a strong positive correlation (p <0.001) between the halflives of AT III and HC II was found, indicating similarities in the catabolic pathways of these two parent molecules.

Keywords

Heparin cofactors - Antithrombin III - Turnover studies - Baboons - Pentosanpolysulfate

• References

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