Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The important roles of thrombin in the development and propagation of thrombosis are well recognized. In addition to being the enzyme for clotting fibrinogen (the major protein component of blood clots), thrombin accelerates its own generation by activating factor V, factor VIII, factor XI and platelets. It accelerates the stabilization of clots by activating factor XIII to factor XIIIa, the enzyme which crosslinks fibrin. There are probably two major pathways for regulating the availability of thrombin in vivo: inactivation of thrombin (by antithrombin III/vessel wall heparan sulfate and perhaps by other endogenous antithrombins) and the inactivation of factor Va and factor VIIIa by activated protein C. Factor Va and factor VIIIa accelerate the production of thrombin. However, when thrombin becomes bound to fibrin (in clots or possibly on cell surfaces), the ability of antithrombin III/heparin to inactivate thrombin is then reduced significantly. Impairment by fibrin of thrombin inhibition by antithrombin III may account in part for the inability of unfractionated heparin to prevent post-operative deep vein thrombosis in up to 20% of patients who undergo major elective orthopaedic surgery, and may also explain the need for oral anticoagulants after unfractionated and low molecular weight heparins are used to initiate the treatment of established deep vein thrombi. The ineffectiveness of the antithrombin III/heparin pathway for inhibiting thrombin under some circumstances has been a contributory factor for the development, evaluation and identification of other inhibitors of thrombin which are more able than antithrombin III/heparin to inactivate thrombin when the enzyme is bound to fibrin. The focus of this review is to detail how these synthetic agents, by directly or indirectly inactivating thrombin, can also effectively inhibit prothrombin activation in vitro.
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PMID:Mechanisms for the anticoagulant effects of synthetic antithrombins. 815 38

Information about the status of the haemostatic balance can be derived from the end products of coagulation and fibrinolysis, i.e. soluble fibrin and fibrin degradation products (FbDP), such as D-dimer, respectively. Assays for FbDP have been available for more than 15 years. Examples are semi-quantitative latex agglutination assays, and quantitative enzyme immunoassays for D-dimer. It is known that the use of serum can lead to erroneous and even false-positive or false-negative results. Little is known about the use of the assays in the Netherlands (type of test; serum or plasma as sample; requested by which specialism; for which indications; cito assay or not; numbers of assays). To collect such data we sent out questionnaires to 116 clinical centres. On the basis of the responses received from 82 centres we can conclude that the vast majority of the centres (76) use semi-quantitative latex tests. Of these 76 centres 59 used plasma samples (28000 tests/year); and 17 used serum (4800 test/year). The assays are done at the request of gynaecologists, internists, intensive care units and cardiologists for a variety of indications such as DIC, pregnancy complications, DVT and PE. In most cases cito assays were involved. The D-dimer assays are discussed with special reference to standardisation, (biochemical) specificity, reproducibility, and the reasons why serum can cause erroneous results. Introduction Under normal conditions there is equilibrium between on the one hand the activity of the coagulation system, and on the other hand the activity of the fibrinolytic system. Disturbance of this equilibrium, designated as the haemostatic balance, can cause bleedings when the fibrinolytic system is relatively more active than the coagulation system, and can cause thrombotic phenomena when coagulation is more active than fibrinolysis. An activated coagulation system leads to thrombin formation. The thrombin formed converts fibrinogen to fibrin, and activates factor XIII to factor XIIIa, which cross-links the fibrin formed. Crosslinked fibrin is insoluble.
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PMID:The Clinical Value of Assays of Fibrin Degradation Products, and Their Use in the Netherlands. 3053 83

D-dimer is an important marker of different coagulation diseases, such as venous thromboembolism (including deep vein thrombosis and pulmonary embolism) and disseminated intravascular coagulation. Though it is frequently used in many clinical diagnostic situations, the D-dimer assays currently lack standardization due to its inherent heterogeneity which makes the antibody-based methods have different quantitative results and cutoffs to define an abnormal value. In this study, we report the first antibody-free D-dimer quantification method. In the method, a cross-linked peptide of fibrin D domain carboxyl terminal cross-linked by the factor XIIIa was used to represent the D-dimer. By using a filter-aided sample preparation and a nickel immobilized metal affinity chromatography enrichment strategy, the complexity of the plasma sample was significantly reduced, and the cross-linked peptide was enriched effectively for analysis with parallel reaction monitoring in mass spectrometry. The linear range of this method was 3.125-400 nmol/L which spans over two magnitudes. Recovery and reproducibility of the method were found to be good. To further demonstrate the performance of our method, D-dimer concentrations of 25 human plasma samples were analyzed, and the results had a good correlation between with the commercial D-dimer assay kit used in hospitals. This method was completely antibody-free and has the potential to promote the standardization of D-dimer analysis.
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PMID:A Mass-Spectrometry-Based Antibody-Free Approach Enables the Quantification of D-Dimer in Plasma. 3251 45