Thrombin generation in a woman with heterozygous factor V Leiden and combined oral contraceptives: A case report.

Combined oral contraceptives and factor V Leiden mutation are multiplicative risk factors for venous thromboembolism. However, it remains unknown whether this multiplicative effect is reflected in thrombin generation assays. We report here the evolution of the thrombin generation profile while taking combined oral contraceptives and after their discontinuation in a woman with heterozygous factor V Leiden mutation. The proband exhibited a distinctly prothrombotic thrombin generation profile including markedly decreased thrombomodulin (TM) sensitivity, compared to the control population. This profile possibly reflected a high thrombotic risk. After discontinuation of combined oral contraceptives, thrombin generation and TM sensitivity improved greatly, leaving only a slightly prothrombotic profile. Therefore, the multiplied thrombotic risk occurring with simultaneous combined oral contraceptives and factor V Leiden mutation is reflected by a thrombin generation assay performed without and with TM. This could be a promising tool to identify women taking combined oral contraceptives at high risk for venous thromboembolism. Further studies are needed to verify this hypothesis

Thrombocytopathies: Not Just Aggregation Defects-The Clinical Relevance of Procoagulant Platelets.

Platelets are active key players in haemostasis. Qualitative platelet dysfunctions result in thrombocytopathies variously characterized by defects of their adhesive and procoagulant activation endpoints. In this review, we summarize the traditional platelet defects in adhesion, secretion, and aggregation. In addition, we review the current knowledge about procoagulant platelets, focusing on their role in bleeding or thrombotic pathologies and their pharmaceutical modulation. Procoagulant activity is an important feature of platelet activation, which should be specifically evaluated during the investigation of a suspected thrombocytopathy

Heparin-Induced Thrombocytopenia: A Review of New Concepts in Pathogenesis, Diagnosis, and Management.

Knowledge on heparin-induced thrombocytopenia keeps increasing. Recent progress on diagnosis and management as well as several discoveries concerning its pathogenesis have been made. However, many aspects of heparin-induced thrombocytopenia remain partly unknown, and exact application of these new insights still need to be addressed. This article reviews the main new concepts in pathogenesis, diagnosis, and management of heparin-induced thrombocytopenia

Evaluation of mechanical and interfacial properties of bio-composites based on poly(lactic acid) with natural cellulose fibers

The circular economy policy and the interest for sustainable material are inducing a constant expansion of the bio-composites market. The opportunity of using natural fibers in bio-based and biodegradable polymeric matrices, derived from industrial and/or agricultural waste, represents a stimulating challenge in the replacement of traditional composites based on fossil sources. The coupling of bioplastics with natural fibers in order to lower costs and promote degradability is one of the primary objectives of research, above all in the packaging and agricultural sectors where large amounts of non-recyclable plastics are generated, inducing a serious problem for plastic disposal and potential accumulation in the environment. Among biopolymers, poly(lactic acid) (PLA) is one of the most used compostable, bio-based polymeric matrices, since it exhibits process ability and mechanical properties compatible with a wide range of applications. In this study, two types of cellulosic fibers were processed with PLA in order to obtain bio-composites with different percentages of microfibers (5%, 10%, 20%). The mechanical properties were evaluated (tensile and impact test), and analytical models were applied in order to estimate the adhesion between matrix and fibers and to predict the material's stiffness. Understanding these properties is of particular importance in order to be able to tune and project the final characteristics of bio-composites

Biomarkers of liver dysfunction correlate with a prothrombotic and not with a prohaemorrhagic profile in patients with cirrhosis.

Different liver dysfunction biomarkers are used to assess the bleeding risk of patients with cirrhosis, either as such or included in bleeding risk assessment scores. Since the current model of coagulation in patients with cirrhosis describes a procoagulant tendency with increasing severity according to Child-Pugh stage, we decided to investigate the relation between liver dysfunction biomarkers and thrombin generation. Our aim was to verify their adequacy for bleeding risk assessment. We performed a prospective single-centre study including 260 patients with liver cirrhosis. Thrombin generation was measured using ST Genesia® Thrombin Generation System without and with thrombomodulin in order to assess the role of proteins C and S. Relations between thrombin generation and Child-Pugh/model for end-stage liver disease (MELD) scores, prothrombin time (PT)/international normalised ratio (INR), activated partial thromboplastin time (aPTT), factor V activity, albumin, and total bilirubin were assessed. Thrombomodulin-mediated inhibition of thrombin generation was significantly decreased in patients with liver cirrhosis compared with healthy donors (p <0.0001) and in Child-Pugh B and C compared with A (p <0.0001 [A-B], 0.4515 [B-C], <0.0001 [A-C]). Thrombomodulin-mediated inhibition significantly decreased with increasing PT/INR, aPTT, and total bilirubin levels and with decreasing factor V activity and albumin levels. Worsening liver dysfunction biomarkers reflect an increasing prothrombotic profile in patients with liver cirrhosis. In particular, prolonged PT/INR and aPTT as well as decreasing factor V activity are related to an increasing thrombotic risk and not to an increasing bleeding risk. These parameters should not be used to assess bleeding risk due to haemostatic anomalies in patients with liver cirrhosis. Alternative biomarkers for bleeding risk assessment in patients with liver cirrhosis need to be developed. We demonstrate that the laboratory parameters used to assess bleeding risk of patients with liver disease, e.g. prothrombin time/international normalised ratio (PT/INR) and activated partial thromboplastin time (aPTT), are inadequate for this purpose because they are correlated with a prothrombotic coagulation profile. In this article, we highlight the need for alternative parameters to assess bleeding risk in patients with liver disease

Tailoring morphology and mechanical properties of PLA/PBSA blends optimizing the twin-screw extrusion processing parameters aided by a 1D simulation software

To promote sustainability, the adoption of biobased and biodegradable plastics is a compelling solution. However, the successful utilization of these materials is contingent upon achieving desired properties and the ability to scale up production processes. Particularly in the case of blend systems, synergising the advantages of different polymers is essential. Moreover, assessing processing behavior and optimizing parameters are pivotal. This study aims to improve the extrusion process parameters selection using a 1D software-assisted Design of Experiments (DoE) approach. Polylactic acid (PLA) and polybutylene succinate-co-adipate (PBSA), varying PLA/PBSA ratios, were analysed simplifying and expediting the parameters selection. Remarkably, even in the absence of compatibility agents, this work demonstrates the potential to modify the structure, thereby influencing properties and performance by manipulating the process conditions

Role of virtual break-up of projectile in astrophysical fusion reactions

We study the effect of virtual Coulomb break-up, commonly known as the dipole polarizability, of the deuteron projectile on the astrophysical fusion reaction 3He(d,p)4He. We use the adiabatic approximation to estimate the potential shift due to the E1 transition to the continuum states in the deuteron, and compute the barrier penetrability in the WKB approximation. We find that the enhancement of the penetrability due to the deuteron break-up is too small to resolve the longstanding puzzle observed in laboratory measurements that the electron screening effect is surprisingly larger than theoretical prediction based on an atomic physics model. The effect of the 3He break-up in the 3He(d,p)4He reaction, as well as the 7Li break-up in the 7Li(p,alpha)4He reaction is also discussed.Comment: 9 pages, 2 eps figure

Characterization of Procoagulant COAT Platelets in Patients with Glanzmann Thrombasthenia.

Patients affected by the rare Glanzmann thrombasthenia (GT) suffer from defective or low levels of the platelet-associated glycoprotein (GP) IIb/IIIa, which acts as a fibrinogen receptor, and have therefore an impaired ability to aggregate platelets. Because the procoagulant activity is a dichotomous facet of platelet activation, diverging from the aggregation endpoint, we were interested in characterizing the ability to generate procoagulant platelets in GT patients. Therefore, we investigated, by flow cytometry analysis, platelet functions in three GT patients as well as their ability to generate procoagulant collagen-and-thrombin (COAT) platelets upon combined activation with convulxin-plus-thrombin. In addition, we further characterized intracellular ion fluxes during the procoagulant response, using specific probes to monitor by flow cytometry kinetics of cytosolic calcium, sodium, and potassium ion fluxes. GT patients generated higher percentages of procoagulant COAT platelets compared to healthy donors. Moreover, they were able to mobilize higher levels of cytosolic calcium following convulxin-plus-thrombin activation, which is congruent with the greater procoagulant activity. Further investigations will dissect the role of GPIIb/IIIa outside-in signalling possibly implicated in the regulation of platelet procoagulant activity

Neutron Tomography at INES: First experimental results

A neutron tomography apparatus has been designed and installed at the Italian neutron experimental station (INES) at ISIS (UK). The instrument has a double aim: an additional opportunity for the INES users and a “bench test” for an instrument component that will be proposed for installation on some of the new neutron scattering instruments of Target Station 2 (TS2) of ISIS. Here, we present the first experimental results achieved with this apparatus