Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fondaparinux is a synthetic pentasaccharide consisting of the minimal sequence of heparin which interacts with antithrombin (AT). It represents a new class of selective factor Xa inhibitors without any antithrombin activity. It has been shown to exhibit potent antithrombotic properties in clinical studies. However, the mechanism of its antithrombotic action has not yet been fully established. In the present study it was shown that fondaparinux, used at pharmacological concentration (500 ng/ml), rendered the clot more susceptible to fibrinolysis induced by t-PA: plasma fibrin clots formed in the presence of fondaparinux and perfused with t-PA were degraded at a faster rate than those formed in the absence of fondaparinux. This fibrinolytic activity of fondaparinux is mainly due to a modification of clot structure characterized by a loose fibrin conformation with less branched fibers and the presence of large pores in comparison to control clots which present a tighter conformation. The difference in fibrin structure was responsible for an increase in clot porosity leading to a better availability of t-PA to the fibrin network. It is related to the decrease in thrombin generation, in an AT-dependent pathway. It was also demonstrated that in the presence of exogenous thrombomodulin, the inhibition of TAFI activation by fondaparinux could contribute, to a lesser extent, to the increased thrombus lysis. The increase in t-PA induced thrombus lysis could contribute to the antithrombotic activity of fondaparinux.
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PMID:Clot structure modification by fondaparinux and consequence on fibrinolysis: a new mechanism of antithrombotic activity. 1720 Jul 67

In contrast to older anticoagulant agents vitamin K antagonists and heparins, the new ones are directed towards a single target in general. The main characteristics of the new agents are: their site of action in the coagulation cascade and their mechanism of action which is indirect, antithrombin dependent, most often such as Fondaparinux and Idraparinux or direct such as Dabigatran, Rivaroxaban; the specificity of the new molecules, since they must not interact with other enzymes: trypsin, kallikrein, t-PA, etc...; their mode of administration parenteral and/or oral; their pharmacokinetics and their clearance frequently by the kidney (Hirudin, fondaparinux) or through hepatic metabolism (argatroban); tolerance including for all compounds the bleeding risk or an unexpected hepatic intolerance for Ximelagatran; the availability of a specific antidote and the cost of the drug; one compound is registered in France Arixtra Fondaparinux in major orthopedic surgery and in the treatment of venous thromboembolism and in prophylactic treatment in medical patients. However, the main indications of interest for these new drugs is atrial fibrillation. There is a real need in this indication and the number of patients to treat is growing with the longer life expectancy.
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PMID:[New antitoagulants]. 1740 41

Fondaparinux is the first selective inhibitor of the coagulation factor Xa which is commercially avaliable for clinical use. It has been approved for the prevention of venous thromboembolism in patients undergoing orthopedic surgery and for the initial therapy of venous thromboembolism. In randomized clinical trials the value of fondaparinux in the treatment of ST-elevation myocardial infarction (STEMI) has been investigated. The PENTALYSE study showed that fondaparinux was at least as effective and safe as unfractionated heparin in 333 patients with STEMI undergoing fibrinolysis with t-PA. In the recent large OASIS-6 trial with 12,092 patients the treatment with 2.5 mg fondaparinux daily significantly reduced death and reinfarctions until day 30 compared with guideline recommended usual care and compared with unfractionated heparin (9.7% vs 11.2%, p = 0.008) without increasing major bleedings (1.0% vs 1.3%, p = 0.13). This advantage was predominantly seen in the subgroups of patients with fibrinolysis and without early reperfusion therapy. However, in the subgroup of primary percutaneous coronary interventions (PCIs) no clinical benefit of fondaparinux was found, but there were more catheter thrombosis and acute thrombotic complications. In summary, fondaparinux is a new antithrombin that is an efficient, safe, and easy to use in treatment for STEMI patients, particularly those not undergoing primary PCI.
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PMID:Management of acute coronary syndromes with fondaparinux. 1770 40