Anticoagulants and the Propagation Phase of Thrombin Generation

The view that clot time-based assays do not provide a sufficient assessment of an individual's hemostatic competence, especially in the context of anticoagulant therapy, has provoked a search for new metrics, with significant focus directed at techniques that define the propagation phase of thrombin generation. Here we use our deterministic mathematical model of tissue-factor initiated thrombin generation in combination with reconstructions using purified protein components to characterize how the interplay between anticoagulant mechanisms and variable composition of the coagulation proteome result in differential regulation of the propagation phase of thrombin generation. Thrombin parameters were extracted from computationally derived thrombin generation profiles generated using coagulation proteome factor data from warfarin-treated individuals (N = 54) and matching groups of control individuals (N = 37). A computational clot time prolongation value (cINR) was devised that correlated with their actual International Normalized Ratio (INR) values, with differences between individual INR and cINR values shown to derive from the insensitivity of the INR to tissue factor pathway inhibitor (TFPI). The analysis suggests that normal range variation in TFPI levels could be an important contributor to the failure of the INR to adequately reflect the anticoagulated state in some individuals. Warfarin-induced changes in thrombin propagation phase parameters were then compared to those induced by unfractionated heparin, fondaparinux, rivaroxaban, and a reversible thrombin inhibitor. Anticoagulants were assessed at concentrations yielding equivalent cINR values, with each anticoagulant evaluated using 32 unique coagulation proteome compositions. The analyses showed that no anticoagulant recapitulated all features of warfarin propagation phase dynamics; differences in propagation phase effects suggest that anticoagulants that selectively target fXa or thrombin may provoke fewer bleeding episodes. More generally, the study shows that computational modeling of the response of core elements of the coagulation proteome to a physiologically relevant tissue factor stimulus may improve the monitoring of a broad range of anticoagulants

Impact of storage on phytochemicals and milk proteins in peach yoghurt

Yoghurt supplemented with peach is a dairy product consumed around the world with a shelf-life of ca. 30 days. During this period protein–polyphenol complexes can be formed and have a detrimental effect on the in vivo solubility of both phenolic and proteins. Yoghurt enriched with peach preparate were produced and stored up to 28 days at 2 °C. Total antioxidant activity decreased 24%, total carotenoids increased 66%, while total phenolics remained unchanged during the yoghurt shelf-life. Carotenoids presented significant differences between peach enriched yoghurt and peach preparate stored under the same conditions. After 28 days the zeaxantin + lutein, β-cryptoxanthin and β-carotene increased 133, 122, and 84% respectively, for peach preparate, while in peach yoghurt they increased 68, 40, and 15%, indicating interactions of carotenoids with matrix components mainly proteins and fat present in yoghurt. Polyphenols presented higher stability when added to yoghurt with slight variations in their content of ca. 10% for (+)-catechin and 12% for p-coumaric acid, and no variations were recorded in neochlorogenic and chlorogenic acids and in rutin. The α-lactalbumin content decreased 22% after 24 h of peach addition while β-lactoglobulin content did not change. Peach polyphenols were very stable during yoghurt shelf-life while carotenoids were the compounds that presented higher interactions with the matrix.info:eu-repo/semantics/publishedVersio