4.4 Article

Platinoid effects on human plasmatic coagulation kinetics: a viscoelastic analysis

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JOURNAL OF THROMBOSIS AND THROMBOLYSIS
卷 51, 期 3, 页码 577-583

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SPRINGER
DOI: 10.1007/s11239-020-02373-4

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  1. Department of Anesthesiology, College of Medicine, at the University of Arizona

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The study compared the effects of different platinum group metals on human plasma coagulation and found that platinum compounds did not have a significant effect on coagulation, while NAMI-A exhibited mild hypercoagulability and ruthenium chloride significantly promoted clotting activity.
In recent years a variety of metals (cadmium, chromium, copper, iron) have been demonstrated to modulate coagulation in vitro and in vivo. One group of metals, the platinoids, have not been assessed, and such investigation is justified given the thromboembolic phenomena associated with platinum-based chemotherapy. Thus, the goal of the present investigation was to assess the effects of carboplatin, cisplatin (platinum compounds), NAMI-A, and ruthenium chloride (ruthenium compounds) on human plasmatic coagulation. Human plasma was exposed to clinically relevant, equimolar concentrations of the aforementioned platinum and ruthenium compounds, with changes in plasmatic coagulation assessed via thrombelastography. The first series of experiments demonstrated no significant modulation of coagulation by the platinum compounds, while NAMI-A demonstrated mild hypercoagulability and ruthenium chloride exerted marked hypercoagulability. A second series of experiments utilizing a variety of specialized modifications of thrombelastography focused on ruthenium chloride revealed that this compound enhances prothrombin activation. While the hypercoagulability associated with platinum compounds in vivo do not appear to have a basis in plasmatic biochemistry, it appears that ruthenium compounds can exert procoagulant properties by enhancing the common pathway of human plasmatic coagulation. Future investigation of Ru based chemotherapeutic agents in development to assess procoagulant activity as part of evaluating their potential clinical safety is warranted.

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