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Haematological Disease
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Tissue factor (TF) on endothelial cells activates factor VII. TF–factor VIIa complexes bind and activate factor X. Acting like a starter motor, this cleaves a small amount of thrombin (from prothrombin), which activates factors VIII and V, and then enzymatic factor IX. If this activation is sufficient, coagulation proceeds to the next stage.
Amniotic Fluid Embolism
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Zaid Diken, Antonio F. Saad, Luis D. Pacheco
DIC is a common finding in up to 83% of AFE cases [3]. It is secondary to consumptive activation of the clotting cascade by either amniotic fluid constituents (e.g. tissue factor) or by the systemic inflammatory response that is triggered during the event. During inflammation, monocytes and neutrophils will express tissue factor in their surface. The latter binds to Factor VII, activating the extrinsic pathway of the clotting cascade. Rarely, coagulopathy can be the only manifestation in AFE [24–26]. AFE patients with DIC are at risk for the following serious hemorrhagic complications: Venipuncture bleeding, gastrointestinal hemorrhage, hematuria, pelvic lacerations bleeding, and uterine bleeding.
Haemostasis and Thrombosis
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Anticoagulant factors:Tissue factor pathway inhibitor (TFPI)Present in plasma and released by platelets, but the majority is on the surface of EC. It binds FXa and then TF-FVIIa and thus acts to dampen any procoagulant stimulus.AntithrombinBinds and inhibits the coagulation proteases, particularly thrombin (FIIa) and FXa. Its action is greatly potentiated by the heparans on the surface of EC and by heparin administered therapeutically.Protein C-Protein SThrombin escaping from the haemostatic event is captured by thrombomodulin on the surface or normal endothelium. This drastically changes its specificity so that it now activates protein C (APC). APC in concert with Protein S degrades FVa and FVIIIa, thus limiting further thrombin generation.
Effect of differently coated silver nanoparticles on hemostasis
Published in Platelets, 2021
Marija Milić, Barbara Vuković, Rinea Barbir, Barbara Pem, Mirta Milić, Vatroslav Šerić, Eleonore Frőhlich, Ivana Vinković Vrček
TGT evaluates the overall balance between procoagulants and anticoagulants in plasma as it continuously measures the activity of thrombin formed in plasma during 30 min. We used tissue factor as a triggering agent of clotting, the same as in PT testing. Two main parameters were obtained: endogenic thrombin potential (ETP) that represents area under the curve of thrombin generation, and maximum thrombin generation (Cmax) that represents peak height. Both ETP and Cmax were significantly decreased only in the presence of high doses of PLL-AgNPs, while treatment of PPP with other AgNPs types did not show any significant changes (Figure 6). In control experiments with ionic Ag form and coating agents, the same trend for PLL was obtained as for PLL-AgNPs (Figure S3 in the SI), suggesting that anticoagulant effect of AgNPs mainly originate from the coating agents used for their stabilization.
Diurnal variations in tissue factor and tissue factor pathway inhibitor concentrations in relation to on-treatment platelet reactivity: an analysis of patients with acute myocardial infarction
Published in Platelets, 2020
Joanna Boinska, Marek Koziński, Michał Kasprzak, Katarzyna Ziołkowska, Inga Dziembowska, Michał Ziołkowski, Jacek Kubica, Danuta Rość
Citrate samples we centrifuged at 2500 × g for 20 min and the resulting plasma was stored at –80°C until analysis. TF concentrations were assessed using enzyme-linked immunosorbent assay kits (Imubind Tissue Factor ELISA kit, American Diagnostica Inc., Greenwich, Connecticut, USA). TF ELISA test detected TF, TFapo and TF/VII complex. TFPI concentrations were assessed using enzyme-linked immunosorbent assay kits (IMUBIND Total TFPI ELISA Kit American Diagnostica Inc. Greenwich, Connecticut, USA). TFPI ELISA detected the full-length TFPI and `truncated’ TFPI forms that remained bonded with TF or factor VII. The measurements were performed according to the manufacturer’s instructions. The lower detection limits were 10 pg/mL for TF concentration and 0.36 ng/mL for TFPI. The intraassay and interassay coefficients of variation for tests were below 10%.
Patients with hemophilia A and inhibitors: prevention and evolving treatment paradigms
Published in Expert Review of Hematology, 2020
David Lillicrap, Karin Fijnvandraat, Guy Young, Maria Elisa Mancuso
Other novel therapies present other challenges. Monoclonal antibodies able to bind to tissue factor pathway inhibitor (TFPI) act by inhibiting one of the natural anticoagulant pathways. As these agents intervene in a complex pathway, their effect is not fully predictable and the balance between bleeding risk and thrombotic risk is delicate [41]. Fitusiran is an investigational small interfering RNA (siRNA) therapy that suppresses the synthesis of antithrombin and, as such, may increase the risk of thrombosis. Fitusiran is administered subcutaneously (once monthly) and is indicated for patients with hemophilia A and B with or without inhibitors [42]. A fatal case of cerebral thrombosis reported in a young non-inhibitor patient participating in a phase 2 open-label extension study of fitusiran led to a temporary suspension of clinical trials, which have since resumed subsequent to a risk mitigation strategy agreed to between the manufacturer of fitusiran and the US Food & Drug Administration. An ongoing phase 3 study has incorporated protocol-specified guidelines and additional investigator and patient education about fitusiran dosing to limit thrombotic risk (Clinical Trial.gov identifier: NCT02554773) [43].