Coagulation factor V is composed of domains A1-A2-B-A3-C1-C2 and is activated by thrombin through proteolytic cleavage at Arg 709, Arg 1018 and Arg 1545. Upon thrombin activation, the B-domain is released and the active factor Va is formed by the heavy (A1-A2) and light chains (A3-C1-C2). Factor Va functions as an essential cofactor to factor Xa in the conversion of prothrombin to thrombin during coagulation. Recently it was shown that coagulation factor V, apart from being a precursor form to the procoagulant factor Va, also has anticoagulant properties, as it functions as a cofactor to activated protein C (APC). APC is a member of the anticoagulant pathway and downregulates the coagulation process through proteolytic inactivation of factors VIII/VIIIa and factors V/Va. In a factor VIIIa degradation assay, the APC-mediated inactivation of factor VIIIa is potentiated by the synergistic cofactors protein S and factor V. Protein S alone has little cofactor activity, whereas in the presence of factor V it is dramatically enhanced. This study provides insights into the molecular mechanisms that regulate the anticoagulant activity of factor V. Thrombin cleavage of factor V occurs in a sequential order. The thrombin cleavage site Arg 1545 is kinetically less favored than the other two sites, and cleavage at this site is the last to occur during thrombin activation of factor V As a consequence of this, different activation intermediates exist that express different levels of procoagulant activity. The anticoagulant activities of these intermediates have now been studied. It was found that factor V could be cleaved by thrombin at both Arg 709 and Arg 1018 and still work fully as a cofactor to APC, whereas cleavage at Arg 1545 completely abolished the anticoagulant activity of factor V. This suggests that the APC cofactor function of factor V depends on the B-domain remaining attached to the A3 domain. This study further shows that APC converts coagulation factor V into a member of the anticoagulant pathway by cleaving factor V in the A2 domain at Arg 506. By cleavage of factor V, APC not only produces an anticoagulant cofactor, but at the same time eliminates the pool of procoagulant factor V, since APC cleaved factor V will have no future as a cofactor in the coagulation. The unique way by which APC and thrombin, through proteolytic cleavage, can convert factor V into either an anticoagulant or a procoagulant adds to the intriguing mechanisms that balance the procoagulant and anticoagulant forces.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1080/00365519950185913 | DOI Listing |
Knee
January 2025
IULS-University Institute for Locomotion and Sports, Pasteur 2 Hospital, University Côte d'Azur, Nice, France; ICARE Team, Côte d'Azur University, Inserm, CNRS, Valrose Institute of Biology, Nice, France. Electronic address:
Background: Several studies have demonstrated the interest in patient-specific custom cutting guides in total knee arthroplasty (TKA), but clinical improvement remains debated. The purpose of this study was to evaluate the functional outcomes (Forgotten Joint Score, FJS) of patients undergoing individualized TKA compared with those receiving off-the-shelf (OTS) implants, both using patient-specific cutting guides with personalized alignment over a minimum follow up period of 12 months. We hypothesized that individualized TKA demonstrates significantly better functional outcomes than OTS TKA (FJS and percentage of patients reaching the minimum clinically important difference).
View Article and Find Full Text PDFCurr Opin Psychol
January 2025
Department of Rehabilitation Medicine, The University of Washington, Seattle, WA, USA.
Psychological chronic pain treatments have variable efficacy across individual patients, and on average tend to produce modest effects. In order to improve treatment outcomes, the past decade has seen a rapid increase in research focused on determining the mechanisms underlying treatment-related gains. The near exclusive focus of this research has been on uncovering patient-related mediators and moderators.
View Article and Find Full Text PDFGeriatr Nurs
January 2025
School of Nursing, Fudan University, Shanghai 200032, China. Electronic address:
Objective: To explore the network structure of common geriatric syndromes and conditions in physically disabled older adults.
Methods: We chose fourteen common geriatric syndromes and conditions from the dataset and estimated networks with the partial correlation network method. We tested the stability and accuracy of the network using the package "bootnet" in R software.
JMIR Form Res
January 2025
Department of Medical and Clinical Psychology, Center of Research on Psychological Disorders and Somatic Diseases (CoRPS), Tilburg University, Tilburg, the Netherlands, 31 134662142.
Background: Health-related data from technological devices are increasingly obtained through smartphone apps and wearable devices. These data could enable physicians and other care providers to monitor patients outside the clinic or assist individuals in improving lifestyle factors. However, the use of health technology data might be hampered by the reluctance of patients to share personal health technology data because of the privacy sensitivity of this information.
View Article and Find Full Text PDFJMIR Cardio
January 2025
Medicine Faculty, University of Geneva, Geneva, Switzerland.
Background: Medication nonadherence remains a significant challenge in the management of chronic conditions, often leading to suboptimal treatment outcomes and increased health care costs. Innovative interventions that address the underlying factors contributing to nonadherence are needed. Gamified mobile apps have shown promise in promoting behavior change and engagement.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!