Thrombin is the product of the hemostatic response essential to the conversion of fibrinogen to fibrin. In addition, it is also responsible for the aggregation of blood platelets in the formation of the "platelet plug" as well as the activation of factor VIII, factor V, factor XI, factor XIII and protein C. The action of thrombin is not confined to the hemostatic response as it also has a critical function in the wound healing process by stimulating 'mitogenic' events through interaction with cell surface receptors. In this review, we consider the various biological activities of thrombin as they relate to current therapeutic use. While there has been considerable interest in the development of fibrin sealant products, there has been considerably less interest in documenting the continuing use of thrombin as a therapeutic. The use of thrombin for topical hemostasis and the treatment of pseudoaneurysms will be discussed in detail. It is concluded that the use of thrombin as a drug will not only continue but also will significantly increase. However, the availability of a safe human thrombin preparation will be critical for the continued use of thrombin as a therapeutic.
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http://dx.doi.org/10.1160/TH03-12-0792 | DOI Listing |
Heart Rhythm O2
December 2024
Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan.
Background: It remains unclear whether the newly adopted high-power, short-duration (HP-SD) setting in ablation for atrial fibrillation (AF) impacts periprocedural thrombotic markers or silent stroke (SS) onset.
Objective: The aim of the present study was to investigate the clinical impact of HP-SD setting ablation on changes in periprocedural thrombotic markers and the onset of SS.
Methods: We enrolled 101 AF patients: the HP-SD group (n = 67) using 50 W and the conventional ablation group (n = 34) using 30 to 40 W.
J Thromb Haemost
January 2025
Case Western Reserve University, School of Medicine, Department of Pharmacology, Cleveland, OH United States. Electronic address:
Background: Hypercoagulation and thrombin generation are major risk factors for venous thrombosis. Sustained thrombin signaling through PAR4 promotes platelet activation, phosphatidylserine exposure, and subsequent thrombin generation. A single-nucleotide polymorphism in PAR4 (rs2227376) changes proline to leucine extracellular loop 3 (P310L), which decreases PAR4 reactivity and is associated with a lower risk for venous thromboembolism (VTE) in a GWAS meta-analysis.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, 53127 Bonn, Germany.
Splanchnic vein thrombosis (SVT), which is particularly prevalent in myeloproliferative neoplasms (MPNs), has a multifactorial pathomechanism involving the anticoagulant protein C (PC) pathway. To better characterize the hypercoagulable state in SVT we assessed its key enzymes thrombin and activated PC (APC). The study population included 73 patients with SVT, thereof 36 MPN+, confirmed by bone marrow biopsy, 37 MPN-, and 30 healthy controls.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy.
Thrombin binding aptamer (TBA) is one of the best-known G-quadruplex (G4)-forming aptamers that efficiently binds to thrombin, resulting in anticoagulant effects. TBA also possesses promising antiproliferative properties. As with most therapeutic oligonucleotides, chemical modifications are critical for therapeutic applications, particularly to improve thermodynamic stability, resistance in biological environment, and target affinity.
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