The History of Thrombin
Roger L. Lundblad in The Chemical Biology of Thrombin, 2022
The fact that blood, when removed from the circulatory system, forms a “clot” has been known for centuries. There were early studies exploring the mechanism of blood coagulation leading to two hypotheses. One school of thought considered the coagulation of blood as a process of solidification caused by cooling or exposure to air or other substances. In 1905, Paul Morawitz attempted to rationalize the information of the past several centuries into a model for the coagulation of blood. While questions regarding thrombin as an enzyme continued into the middle of the 20th century, this did stop continuing work on the mechanism of thrombin formation. In support of earlier work, Ferguson and coworkers50 identified prothrombin as a precursor of thrombin, which was activated by a thromboplastic enzyme in the presence of calcium ions and phospholipid. A major problem in the early work in blood coagulation was a lack of understanding of the role of divalent cations in coagulation.
Disorders in tHemostasis System and Changes in the Rheological Properties of the Blood in Ischemic Heart Disease and Diabetes Mellitus Patients
E.I. Sokolov in Obesity and Diabetes Mellitus, 2020
This chapter examines disorders in tHemostasis system and shows the changes in the rheological properties of the blood in Ischemic heart disease and diabetes mellitus patients. Hemostasis is an evolutionally developed and genetically determined adaptation system of an organism. It includes an integrated unity of the various physiological constants of an organism that ensure the functions of the organism under conditions of stress. The regulation of the hemostasis system is a closed dynamic organization of central and peripheral mechanisms. Antithrombin III is the most powerful inhibitor of blood coagulation, it is synthesized by the endothelium and hepatocytes, is on the surface of the endothelial cells and in the blood, and is responsible for 75–90% of the spontaneous anticoagulant activity of the blood. The anticoagulating effect of heparin is aimed at inactivating thrombin, which is manifest only in the presence of antithrombin III.
Antithrombotic therapy
Gregory YH Lip in Atrial Fibrillation in Practice, 2020
Atrial fibrillation (AF) is the most common cardiac disorder leading to stroke and thromboembolism. Most of the stroke and thromboembolic events in patients with AF are due to thrombus formation in the fibrillating left atria. The prime role of heparin in AF is when immediate anticoagulation is desired until adequate International Normalised Ratio (INR) is attained with warfarin or patient needs to undergo urgent cardioversion. Therapy is administered by an intravenous infusion and monitored by measurement of the activated partial thromboplastin time, which is sensitive to the levels of thrombin, factor Xa, and factor IXa. Low molecular weight heparin preparations, which are administered subcutaneously and act by facilitating the inhibition of coagulation factor Xa by antithrombin, have been introduced with good results in AF. Careful patient selection, patient education, INR monitoring, and regular medical supervision play vital roles in reducing the bleeding risks of anticoagulation therapy for AF.
Topical use of recombinant human thrombin for operative hemostasis
Published in Expert Opinion on Biological Therapy, 2009
Christopher D Anderson, Lyndsey J Bowman, William C Chapman
Background: The topical use of thrombin has a long history in surgery as an adjunct for achieving operative hemostasis. Until recently the majority of thrombin used topically was derived from bovine plasma. This preparation has been proven to be immunogenic and has led to safety concerns in recent years. Recombinant human thrombin (rhThrombin) has recently been developed as an alternative for topical use for surgical hemostasis. Objective: To review the clinical safety and efficacy data relating to rhThrombin using bovine-derived thrombin as a comparative standard. Methods: This review summaries recent literature regarding topical use of rhThrombin using bovine thrombin as the ‘gold standard’ for topical surgical hemostasis. Conclusions: The data indicates that topical rhThrombin is as effective as bovine thrombin for hemostasis and significantly less immunogenic.
Binding of Biotinylated Thrombin Receptor Peptide to Cloned Human Thrombin Receptor Overexpressed in Baby Hamster Kidney Cells
Published in Journal of Receptors and Signal Transduction, 1995
Masahiro Takada, Osamu Ito, Motoji Kogushi, Hiroko Kobayashi, Toshie Yamada, Hiroshi Tanaka, Shinji Yoshitake, Isao Saito
Baby hamster kidney (BHK) cells transfected with an expression vector for the human thrombin receptor, and then treated with basic fibroblast growth factor, were found to express specific and saturable binding sites for biotinylated thrombin receptor peptide (SFLLRNPNDKYEPF). Analysis of the binding to live BHK cells yielded an equilibrium dissociation constant (Kd) of 3.0±0.3 μmol/l and a maximal binding capacity (Bmax) of 31.0±0.5 nmol/mg of protein. In competitive binding experiments, the thrombin receptor agonist peptide (SFLLRN), which is a strong inducer of human platelet aggregation, was the most potent competitor. In contrast, position 1 to 2 inverted peptides such as FSLLRNPNDKYEPF and FSLLRNP, which fail to induce for the platelet aggregation, were less potent. This simple and convenient binding assay system using the biotinylated thrombin receptor peptide as a labeled ligand and the cloned thrombin receptor overexpressed in BHK cells may be useful for exploring specific antagonists of the receptor.
Exogenous bovine thrombin as a biomarker of exposure and outcome
Published in Expert Review of Molecular Diagnostics, 2008
Sheila M Crean, Shannon L Michels, Matthew W Reynolds
Bovine thrombin has been used for more than 60 years as a surgical hemostat and sealant. Rare postsurgical events have been attributed to antibovine thrombin immunoglobulins cross-reacting with human homologs. In a literature review of 37 papers reporting safety outcomes in surgical patients, we extracted each paper for a quantitative measurement of bovine thrombin exposure and coagulopathic outcomes. We found that 59.5% of papers documented the commercial source of bovine thrombin and only 19% provided an estimate of exposure in units. Conventional tests for hypocoagulation were common (86%); however, only 9% of papers confirmed this inhibition as an isolated antibody. In addition, only 9% of papers cited a specific biomarker for thrombosis.
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