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Medicines for CHD
Published in Mark C Houston, The Truth About Heart Disease, 2023
Antithrombotic drugs in routine use includeAntiplatelet drugs (aspirin, clopidogrel, and glycoprotein IIb/IIIa receptor antagonists).Anticoagulants (unfractionated and low molecular weight heparin, warfarin, and direct thrombin inhibitors).Factor X inhibitors.
Inflammation
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Factor X deficiency disease has also been described, and individuals with this deficiency have a bleeding tendency similar to that of classic hemophilia.99,143 The congenital defect of Factor II (thrombin) is very rare. Most of the individuals with this disorder have 2 to 10% prothrombin activity, and the susceptibility to bleeding shows some parallelism to the level of prothrombin.238,251,415 Factor XI and Factor XII deficiencies have also been observed. Deficiency of Factor XI is a relatively uncommon disorder and is manifested as a hemorrhagic disorder. The hemorrhagic tendency is, however, much less severe than in hemophilia.129 Congenital deficiency of Factor V is also rare, and the associated bleeding tendency is only moderately severe.354
Coagulation Theory, Principles, and Concepts
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Factor X is the protease component of the complex that converts prothrombin to thrombin. Factor X circulates as a two-chain, disulfide-linked precursor (MW = 59,000) which is activated to factor Xa by either the intrinsic or extrinsic blood coagulation systems. It is produced in the liver, and circulates at a plasma concentration of about 8 μg/mL. The half-life appears to be on the order of 24–40 hr (51).
Rivaroxaban protects from the oxysterol-induced damage and inflammatory activation of the vascular endothelium
Published in Tissue Barriers, 2021
Paulina Gorzelak-Pabis, Marlena Broncel, Katarzyna Wojdan, Adrian Gajewski, Maciej Chalubinski, Mateusz Gawrysiak, Ewelina Wozniak
Dysfunction of the vascular endothelium is an important contributor to the pathobiology of atherosclerotic cardiovascular disease.3 Molecular studies have shown that both factor Xa (FXa) and thrombin are involved in inflammatory processes and endothelial activities, including inflammation, vascular remodeling, and atherosclerosis, presumably mediated through protease activated receptors (PARs). Thrombin is an activator of PAR1, whereas FXa activates PAR1, −2, and −3 alone or in complex with TF-FVIIa.4,5 It should be noted that Factor X is not converted to FXa constitutively but is only activated by intrinsic clotting factors and during a cellular injury. The function of rivaroxaban in the inactivated coagulation cascade is unclear. Seki et al. suggest that rivaroxaban per se may not influence gene modulation in the inactivated coagulation state, while rivaroxaban may suppress the expression of pro-inflammatory genes such as MCP-1, ICAM-1, and IL-8, but only in endothelial cells activated by FXa. Interestingly, Daci et al. imply that pre-treatment with rivaroxaban attenuates LPS-induced acute vascular inflammation by a significant reduction of IL-6, MCP-1 and VCAM-1 levels in rat plasma. These anti-inflammatory effects might perhaps have an impact on vascular functions and prevent the development of atherosclerosis.6
Overcoming the challenges of treating hemophilia in resource-limited nations: a focus on medication access and adherence
Published in Expert Review of Hematology, 2021
Kanjaksha Ghosh, Kinjalka Ghosh
Improving blood transfusion services in any country not only improves care of PWH and other bleeding disorders it also improves overall health service wherever blood or blood products are required. Once the various services of blood banking is slowly developed in the country initial products i.e. FFP, Cryoprecipitate, Cryodepleted plasma can be used for management of some of the cases, they could even be made safer by proper donor control, holding the product till the regular donor comes back for next transfusion and serologically test negative, instituting NAT testing facility, initially may be done in small batches and then individual donors may be tested. In many resource constrained countries, particularly in Asia, rare inherited bleeding disorders are often not so rare because of consanguinity [30]and they need different concentrates that are not readily available but can be provided by FFP or cryoprecipitate. For example severe factor XIII deficiency can easily be treated with once a month FFP infusion as factor XIII has a long half-life of 10–13 days, low levels of this factor can adequately prevent bleeding. Similar argument may be made for factor X deficiency. These FFPs can be freeze dried or can be made virologically safe by solvent detergent [31] and wet heat treatment in a cost effective manner.
Monocyclic beta–lactams for therapeutic uses: a patent overview (2010–2020)
Published in Expert Opinion on Therapeutic Patents, 2021
Katarina Grabrijan, Nika Strašek, Stanislav Gobec
The small molecule inhibitors of FXIa are superior to the macromolecular inhibitors for the reasons already described. There are already several novel oral anticoagulants that target Factor Xa, but have a high risk of bleeding without the available antidote. A safer alternative – inhibitors of intrinsic coagulation rather than common coagulation pathway, is represented by FXIa inhibitors. Although in the early stages of development, clinical trials with any type of inhibitor targeting FXIa are showing promising results, as the inhibitors have a broad therapeutic index and are useful in the treatment of stroke, acute coronary syndrome, atrial fibrillation and the prophylaxis of venous thromboembolism. Monocyclic beta-lactams are showing promising results, as EP −7041 has already passed the Phase 1 clinical trial, and new monocyclic beta-lactams for oral administration are being developed.