Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prothrombin times of 63 patients on oral anticoagulant therapy were tested using 4 different thromboplastins; 2 rabbit brains (Simplastin & Ortho), human placenta (Thromborel) and human brain (Australasian Reference Thromboplastin--ART). Four machines measuring the one-stage prothrombin times were compared with the manual method. Each of the machines and thromboplastins showed highly reproducible and predictable results, but there were differences in thromboplastin sensitivities which would pose major therapeutic problems. A system of correcting ratios of different thromboplastins to a reference preparation would overcome these differences in thromboplastin sensitivities. All thromboplastins gave comparable results with the Clotek, MLA 600 and Coag-A-Pet machines and manual method. Cortek gave comparable ratios with the ART but not with any other thromboplastin.
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PMID:Prothrombin times: an evaluation of four thromboplastins and four machines. 746 53

The effect of a novel recombinant soluble human thrombomodulin, ART-123, on protein C activation was investigated by measuring plasma prothrombinase activity in four healthy male volunteers. ART-123 at a dose of 0.3 mg was administered as a bolus intravenous injection for 1 minute. Plasma ART-123 concentration and prothrombinase activity were determined before and immediately, 24, and 48 hours after injection, and thromboelastography was recorded before and immediately and 24 hours after injection. The mean elimination half-life was 19.82 +/- 2.10 hours. Compared with pretreatment levels, ART-123 reduced prothrombinase activity by 44.2 +/- 11.7%, 52.1 +/- 10.8%, and 61.0 +/- 14.7%, respectively, immediately, 24, and 48 hours after injection, suggesting that ART-123 activated the protein C pathway. ART-123 did not affect thromboelastography values. There were no abnormal findings for objective signs or laboratory tests, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, coagulation and hemostatic parameters, blood chemistry, and urinalysis. Based on these observations, ART-123 at a dose of 0.3 mg can activate the protein C pathway in healthy volunteers.
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PMID:A novel recombinant soluble human thrombomodulin, ART-123, activates the protein C pathway in healthy male volunteers. 965 May 44

Unfractionated heparin, low molecular weight heparin and vitamin K antagonists are anticoagulants currently used for the prevention and treatment of deep vein thrombosis and pulmonary embolism. Considerable limitations of these agents, such as a narrow therapeutic window, a variable dose response or lack of oral bioavailability, created the need for new anticoagulants. Numerous new compounds with different mechanisms of action have been developed and some have been already approved for clinical use. Quite recently, fondaparinux, an indirect anti-factor Xa inhibitor, has been licensed in Europe and in the US for prevention of VTE in patients undergoing hip or knee replacement surgery. In addition, lepirudin, a recombinant hirudin derivative, and the heparinoid danaparoid, have been approved in Austria for treatment of heparin-induced thrombocytopenia. Recombinant nematode anticoagulant protein c2, the orally available thrombin inhibitor ximelagatran and ART-123, a recombinant soluble thrombomodulin, are in advanced stages of clinical development. This article reviews mechanisms and sites of action, and the current state of preclinical and clinical research of these and various other agents with respect to the prevention and treatment of venous thromboembolism).
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PMID:Novel anticoagulants for the prevention and treatment of venous thromboembolism. 1464 23

The therapeutic armamentarium of parenteral anticoagulants available to clinicians is mainly composed by unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux, recombinant hirudins (i.e. bivalirudin, desirudin, lepirudin) and argatroban. These drugs are effective and safe for prevention and/or treatment of thromboembolic diseases but they have some drawbacks. Among other inconveniences, UFH requires regular anticoagulant monitoring as a result of variability in the anticoagulant response and there is a risk of serious heparin-induced thrombocytopaenia (HIT). LMWH, fondaparinux and recombinant hirudins are mainly cleared through the kidneys and their use in patients with severe renal insufficiency may be problematic. LMWH is only partially neutralized by protamine while fondaparinux and recombinant hirudins have no specific antidote. Novel anticoagulants in development for parenteral administration include new indirect activated factor Xa (FXa) inhibitors (idrabiotaparinux, ultra-low-molecular-weight heparins [semuloparin, RO-14], new LMWH [M118]), direct FXa inhibitors (otamixaban), direct FIIa inhibitors (flovagatran sodium, pegmusirudin, NU172, HD1-22), direct FXIa inhibitors (BMS-262084, antisense oligonucleotides targeting FXIa, clavatadine), direct FIXa inhibitors (RB-006), FVIIIa inhibitors (TB-402), FVIIa/tissue factor inhibitors (tifacogin, NAPc2, PCI-27483, BMS-593214), FVa inhibitors (drotrecogin alpha activated, ART-123) and dual thrombin/FXa inhibitors (EP217609, tanogitran). These new compounds have the potential to complement established parenteral anticoagulants. In the present review, we discuss the pharmacology of new parenteral anticoagulants, the results of clinical studies, the newly planned or ongoing clinical trials with these compounds, and their potential advantages and drawbacks over existing therapies.
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PMID:New parenteral anticoagulants in development. 2104 18