What Is The Role Of FXI As A Therapeutic Strategy For Antithromboembolism?

Enoxaparin is a low molecular weight heparin used to prevent thrombosis, particularly post surgery. Enoxaparin binds to antithrombin III which is responsible for inhibiting coagulation by acting on factor Xa. Enoxaparin accelerates the activity of antithrombin III therefore preventing clot formation (McKenna & Lim, 2014 p766). When a blood vessel is damaged, platelets in circulating blood stick to the site of injury and release chemicals that attract more platelets causing aggregation. There are both intrinsic and extrinsic pathways causing thrombi to form to maintain a closed cardiovascular system (Hollar, 2017). Immobility increases risk of thrombus formation as the blood becomes stagnant with gravity and decreased

In this patient, the drugs that he is on can lead to many severe side effects. Firstly he is on a number of medications that can cause CNS depression, hypotension, bradycardia, and sedation potentially leading to falls.

Disseminated intravascular coagulation (DIC) is an acquired syndrome that occurs when a stimulus pathologically activates intravascular coagulation and fibrinolysis resulting in an unbalanced hemostasis (Cunningham, 1999; Huether & McCance, 2008; Wada, 2008). The initiation of DIC starts with the release of tissue factor (TF) by the endothelial cells or white blood cells (WBCs). TF are present on many different cell types including lungs, brain, and placenta. The release of TF is subsequent to a variety of causes including trauma, ischemia, excessive metabolic stress, tumors, infectious organisms, exposure to cytokines and endotoxins (Baglin, 1996; Vinay, Abul, Nelson, & Richard, 2007). The release of endotoxin is the means by which

Adhering platelets release growth factors that enhance smooth muscle proliferation in the vessel wall. Consequently, platelet aggregation is able to contribute to the development and progression of atherosclerosis

Each treatment should be treated case-by-case to ensure that the patient is receiving the best possible care. Suggested treatments consist of regular infusions of DDAVP and/or clotting factor, first aid for minor cuts, physical therapy, fibrin sealants and clot-preserving medications. For Hemophilia C, clotting factor XI is available only in Europe and in the United States bleeding episodes are treated through plasma infusions. Clotting factor XI is not available in the United States because Factor XI concentrates are blood products with a concentrated form of Factor XI. Meanwhile, available only in certain areas of Europe, these blood concentrates are made through a series combining thousands of different blood donors. Therefore, the United States only keeps frozen plasma instead. Fibrin sealants work by applying the medication directly to the site of the wound, from there the Fibrin promotes clotting and healing. Clot-preserving medications can also be applied directly to the wound. However, this time the medication preserves the clot from breaking down and assists in ending the

Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the resulting protein(s).” (U.S National Library of Medicine, 2016) The protein associated with the scenario is the factor VIII gene. The factor VIII gene presents instructions for making a protein called coagulation factor VIII. In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor (vWF). The active protein interacts with another coagulation factor called Factor IX, and as a result, this interaction releases a chain of chemical reactions that form blood clots. “The altered or missing protein cannot participate effectively in the blood clotting process. As a result, blood clots cannot form properly in response to injury.” (F8, 2016) These issues with blood clotting may lead to serious bleeding which could be difficult to stop. In order for the blood clot to be produced to assist aiding the injury, it is in need of both factors to interact with each other. Having the deletion mutation process taken place, Danielle’s factor VIII gene was removed and as a result, she was found to be a carrier of Haemophilia.

Representatives from Thrombolysis in Myocardial Infarction (TIMI), Duke Clinical Research Institute (DCRI), and Merck & Co., Inc.

More patients are being started on factor Xa inhibitors due to their efficacy and safety profile compared to other agents, such as warfarin and enoxaparin. With the expanded use of these agents, there has come an increase in the occurrence of hospital admissions and deaths related to bleeding. It is estimated that in 2016, there were approximately 117,000 hospital admissions for bleeding caused by factor Xa inhibitors.1 Additionally, there were about 2,000 bleeding- related deaths per months.1 Up until May 2018, there was not an agent to reverse the effects of factor Xa inhibtors. In early May, the Food and Drug Administration (FDA) approved Andexxa, andexanet alfa, for the reversal of rivaroxaban and apixaban in the setting of life-threatening or uncontrolled bleeding.1

NOACs are considered to be ideal for prevention of stroke associated with AF and other thromboembolic conditions. Some of the prominent advantages include their predicatable pharmacodyanmic and pharmacokinetic profils, relatively wider therapeutic window that do not require routine monitoring, limited drug interaction and have no dietary restrictions(17). Results from clinical trials showed that NOACs such as thrombin inhibitors (dabigatran), and factor Xa inhibitors (rivaroxaban, apixaban) were found to be at least as effective as warfarin in preventing AF related stroke. Most importantly, intracranial bleeding, the most severe side effect of warfarin was found to be less prevalent in patients treated with NOACs (18-21). In view of such findings, NOACs seem to have an important share in the management of patients with AF. However, use of warfarin for thromboprophylaxis is still considered to be vital as there are certain issues related with the use of NOACs in AF. Warfarin has been used for a couple of decades resulting in extensive experience for prevention of thromboembolism. Some pharmacokinetic controversies regarding NOACs include; shorter acting than warfarin, hence missed doses could increase the risk of thrombosis. Moreover, NOACs have no specific antidotes to reverse their therapeutic effect. One study

Tissue plasminogen activator is a fibrinolytic drug which is used to treat thromboembolic disorders, such as ischaemic strokes. These agents initiate secondary fibrinolysis to occur; altering the haemostatic capability. The primary purpose of this agent is to clear occluded blood vessels within the systemic circulation (Bryant & Knights 2011, pp.534-536).

Thrombosis is the leading cause of morbidity and mortality worldwide and is also associated with the three major cardiovascular diseases: ischemic heart disease, stroke, and venous thromboembolism (VTE). In 2010, GBD documented 52.8 million deaths worldly, 12.9 million deaths were caused by ischemic heart disease and stroke collectively [56]. Thrombosis is the accumulation of blood clot in blood vessels and can be arterial or venous thrombosis. Arterial thrombosis is a thrombotic event in the artery wall and the primary trigger for such event is the rupture of an atherosclerotic plaque which formed because the accumulation of lipid deposits and lipid-laden macrophages (foam cells). On the other hand, venous thrombosis is the thrombotic event

Thrombin is a naturally occurring protein that is present in the blood of humans and animals. The main function of thrombin is as an intermediate step during hemostasis, which slows bleeding by forming blood clots. Thrombin acts as an enzyme during an injury, converting fibrinogen to fibrin, which then causes blood clots to form. Due to its properties, thrombin’s application to the medical field includes topical surgery in the case of minor injuries as well as various other medical procedures such as neurosurgical operations. Apart from applications in the medical field, thrombin also plays significant roles by directly interacting with endothelial cells throughout the body.

Efforts to find a drug capable of increasing the ability to cope with oxidative stress have long been made in the treatment of FRDA. Based on the characteristics of SS-31, a mitochondrion-targeted antioxidant, we chose it to treat the cells derived from FRDA patients as a potential drug. Very strikingly, we found that SS-31 treatment increased the expression of FXN (Fig. 1). This pushed us to evaluate the value of the peptide. First, we optimised the condition for inducing the expression of FXN and found that the protein level of FXN increased in a dose dependent manner in both lymphoblasts and fibroblasts derived from patients (Fig. 1a and Fig. S1). The

Boehringer Ingelheim (BI) and Eli Lilly, manufacturers of empagliflozin (Jardiance) and empagliflozin/metformin (Synjardy)were the primary sources of funding for the study

During early atherogenesis, endothelial activation results in platelet activation and recruitment of platelets to the vessel wall. This early recruitment establishes a positive feedback loop in which the platelets release substances that cause further endothelial activation. Inhibiting early platelet adhesion decreased atherosclerotic plaque formation and is therefore thought to be a key step in the initiation of atherogenesis [209, 210]. While a number of receptor-ligand pairs are important, platelet integrins play a key role in firm adhesion. After rolling along the endothelium, platelets become activated leading to inside-out signaling which causes a conformational change in IIb3. This activated form of IIb3 facilitates the firm adhesion of platelets to the endothelium through a fibrinogen cross-bridge with endothelial v3