The effects of apixaban on clot characteristics in atrial fibrillation: A novel pharmacodynamic biomarker.

Atrial fibrillation (AF) is a major risk factor for stroke. We aim to characterize AF patients and the effects of apixaban therapy in terms of clot microstructure using gel point analysis, a novel biomarker. Seventy-eight patients were included in the study, 50 Stroke with AF (AF-S), and 28 AF without stroke (AF). Pre- and post-anticoagulation samples were collected: gel point (GP) analysis was performed to obtain (i) TGP (the time taken to reach the GP or the clot formation time) and (ii) df, the fractal dimension of the clot, a quantification of clot fibrin microstructure at the GP. At baseline, the AF-S group had a df  = 1.70 (±0.05) and TGP = 306 (±73 s). The AF group had a df = 1.70 ± 0.05 and TGP = 346 ± 78 s, showing a significantly shortened TGP in the stroke group (p = .008). For both groups, apixaban significantly prolonged TGP, p = .005, but resulted in no change in df. Apixaban prolonged clotting time while having no significant impact on the blood's ability to form stable clots (no change in df ). This indicates that apixaban provides protection from the formation of thrombi by reducing clotting kinetics.

Practical treatment guidance for cancer-associated thrombosis - Managing the challenging patient: A consensus statement.

Cancer-associated thrombosis (CAT) is a leading cause of death amongst people with cancer. Treatment decisions have become increasingly complex with the introduction of direct oral anticoagulants and existing guidelines are limited to evidence from patients meeting stringent trial-entry criteria. To assist decision making for healthcare professionals managing CAT in challenging 'real-world' situations, an expert working group of clinicians from oncology, haematology and pharmacology convened over a series of virtual meetings between September 2020 and January 2021 to catalogue the most challenging clinical problems and define consensus recommendations. Clinical problems were divided amongst the group members according to their areas of expertise, with each reviewing the literature and writing their recommendations. Using a web-based file-sharing platform, each contribution was reviewed until consensus was reached. Each clinical problem is discussed; these include managing gastrointestinal impairment, renal impairment, liver impairment, increased risk of bleeding, extremes of body weight, drug interactions, anticoagulation beyond the initial six months and managing recurrent thrombosis. A user-friendly, practical, colour-coded algorithm was produced to help guide clinical decision-making in CAT. Red highlights decision steps where shared decision making, such as with the multi-disciplinary team, is recommended. Amber steps reflect uncertainty of existing evidence. Multiple amber steps per patient warrant increased caution. Making anticoagulation decisions in people with cancer is challenging; it is important that healthcare providers can discuss where there is a lack of evidence and ensure that patient preference is given priority. This algorithm and consensus recommendations are a useful tool to guide these complex discussions.

Stabilisation of SWNTs by alkyl-sulfate chitosan derivatives of different molecular weight: towards the preparation of hybrids with anticoagulant properties.

We have previously demonstrated that chitosan derivative N-octyl-O-sulfate chitosan (NOSC), which presents important pharmacological properties, can suspend single walled carbon nanotubes (SWNTs) up to 20 times more effectively than other chitosan derivatives in an aqueous environment. In an attempt to further investigate the impact of different molecular weights of chitosan to the solubilization and anticoagulant properties of these hybrids an array of NOSC derivatives varying their molecular weight (low, medium and high respectively) was synthesised and characterised by means of FT-IR spectroscopy, NMR spectroscopy and thermal gravimetric analysis (TGA). Microwave and nitric acid purified SWNTs, characterised by FT-IR spectroscopy, transmission electron microscopy (TEM) and Raman spectroscopy, were colloidally stabilised by these polymers and their anticoagulant activity was assessed. The results revealed that the low molecular weight NOSC coated SWNTs exhibit the highest activity when 0.5 mg mL(-1) NOSC solutions are used, activity which is similar to that of the free polymer. Preliminary studies by exposure of these hybrids to Brine Shrimp (Artemia) cysts revealed no effect on the viability of sub-adult Artemia. Our findings suggest the possibility of tailoring these nanomaterials to bear the required properties for application as biocompatible building blocks for nanodevices including biosensors and biomaterials.

N-Octyl-O-sulfate chitosan stabilises single wall carbon nanotubes in aqueous media and bestows biocompatibility.

A non-covalent approach to debundle single wall carbon nanotubes using a biocompatible chitosan-derivative, namely N-octyl-O-sulfate chitosan (NOSC), was investigated. The resulting stable dispersions were characterised by Raman spectroscopy, UV-Vis spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM) and zeta-potential measurements. Both AFM and TEM studies revealed the presence of individual carbon nanotubes wrapped with the polymer (diameters up to 7 nm). Raman spectra showed radial breathing mode frequency shifts, after the addition of NOSC, due to the wrapping of the biomolecules onto the graphitic sidewalls. Molecular modelling studies were employed to investigate the mode of binding of the NOSC chains to the surface of the nanotubes. In agreement with the experiments, modelling studies predicted that the wrapped tube has a maximum thickness of approximately 7 nm. Studies on the anticoagulant properties of these complexes revealed that NOSC coated SWCNTs exhibit similar activity to the polymer alone, this property would eliminate the risk for SWCNTs to induce coagulation as a host reaction process when used in vivo.