Abstract
In summary, the following points have been presented. PK 10169 produced somewhat weaker effects on the coagulant tests in comparison to heparin in various whole blood and citrated plasma assays. In the synthetic substrate assays, PK 10169 produced a pronounced inhibition of various serine proteases in the AT III supplemented system. No significant inhibition was noted in the non-AT III systems. Preliminary data show that PK 10169-AT III complex is capable of producing direct inhibition of the generation of factors Xa and XIIa. In all platelet function tests studied, this agent failed to produce any modulating effects. PK 10169 did not produce an effect on the fibrinolytic system in vitro. However, analysis of blood samples obtained from animals treated in vivo with this agent suggests activation of fibrinolysis. Thus, the mechanism of action must involve certain cellular components or endogenous modulation of the heparin fraction. The newly developed FPA generation test can be modified by various activators or blood systems to mimic closely in vivo physiology. PK 10169 produces a dose response that is more sensitive and more global by this method than the amidolytic anti-Xa or anti-IIa. In contrast to heparin, larger amounts of platelet factor 4 and protamine sulfate are needed to neutralize the anti-Xa and anti-IIa actions of this agent. Additionally, the anti-IIa component is more susceptible to neutralization than the anti-Xa component. Our studies also suggest that PK 10169 is resistant to the action of certain heparin digestive systems, such as heparinase.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.