China
Africa
Explore chapters and articles related to this topic
Inflammation
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
There are some subjects with Factor XIII deficiency.108 This deficiency is hereditary and patients with this disorder often severely hemorrhage after an injury, and they also show defective wound healing. In some of these individuals an inactive protein related to Factor XIII has been demonstrated.
Acquired Circulating Anticoagulants Other than Lupus Anticoagulants
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
Clinically more important inhibitors of the fibrin(ogen) phase of the clotting mechanism are those directed against factor XIII and its activation by thrombin. It is well known that deficiency of factor XIII leads to poor wound healing and recurrent hemorrhage. Therefore, antibodies directed against the factor XIII cross-linking of fibrin might be expected to be similarly complicated. These inhibitors have been classified by Lorand into three categories.116 Type 1 interferes with the activation of factor XIII and induces a severe bleeding tendency.117 Type 2 inhibits activated factor XIII and may cause serious hemorrhage. Type 3 blocks the reactivity of the fibrin substrate towards factor XIII and the clinical manifestations are less severe.118 Several of these cases have been in patients who have taken isoniazid.3 One has been reported as part of a lupus-like syndrome following practolol therapy.119
Coagulation Theory, Principles, and Concepts
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Factor XIII is a transglutaminase that catalyzes the formation of intermolecular ε-(γ-glutamyl) lysine bonds. Plasma factor XIII consists of four subunits, two a and two b subunits. Patients deficient in factor XIII are characterized by bleeding tendencies, abnormal wound healing, and spontaneous abortions (64–66).
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.
Current and emerging biologics for the treatment of hemophilia
Published in Expert Opinion on Biological Therapy, 2019
Giancarlo Castaman, Silvia Linari
An injured blood vessel also exposes membrane-bound tissue factor (TF) in the extravascular tissue to traces of activated factor VII (FVIIa) that are always present in the plasma [26]. By binding to TF, FVIIa becomes a potent activator of factor X (FX) and initiates the path to the earliest production of thrombin catalyzing the activation of both FIX and FX [27]. This activation pathway is historically termed the extrinsic pathway of coagulation. Although this ‘TF pathway’ is quickly shut down by a specific inhibitor (tissue factor pathway inhibitor, TFPI), coagulation accelerates to a rapid pace because nascent thrombin activates factors V, VIII and XI to produce additional thrombin. Moreover, FIXa also activates FX, in the presence of its cofactor FVIIIa. FXa, also in presence of its cofactor FVa, then activates prothrombin to generate thrombin [28]. Interaction among the procoagulant proteins is facilitated by platelet activation, which transforms the platelet surface into a platform for the assembly of coagulant complexes. When thrombin cleaves two small peptides from fibrinogen, fibrin monomers are formed and begin to polymerize. Fibrin polymers become cross-linked by activated factor XIII (FXIIIa) with stable clot generation and achievement of hemostasis.
Improving fibrinolysis in venous thromboembolism: impact of fibrin structure
Published in Expert Review of Hematology, 2019
The key role of the fibrinolytic system is to dissolve fibrin within thrombi by plasmin, in order to maintain vascular patency. Fibrin is produced from fibrinogen by the cleavage of two sets of amino-terminal peptides, fibrinopeptides A and B from the Aa- and Bb-chains, respectively, by thrombin, exposing binding sites in the E-region (knobs) that interact with polymerization pockets (holes) in each of the D-regions. The subsequent formation of fibrin protofibrils then leads to their lateral aggregation and the generation of fibrin fibers, supported by interactions of the αC-regions [1,2]. The fibrin α- and γ-chains are cross-linked by thrombin-activated factor XIII (FXIIIa), which improves mechanical properties and increases clot resistance to fibrinolysis. Fibrinolysis could be considered the complex process of plasmin generation by plasminogen activators, and the subsequent digestion of fibrin by plasmin [3]. The main enzyme involved is plasmin, a serine protease derived from its inactive precursor, plasminogen, through the action of its activators. Plasmin also cleaves several other substrates, including extracellular matrix proteins, and activates some proteases and growth factors, being involved in wound healing, inflammation, and angiogenesis.