Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first case of Fletcher factor deficiency from the African continent is described. This was the only case of symptomatic Fletcher factor deficiency detected in a total population survey of 40,522 persons. This patient differs from other reported cases in that the child had symptoms of severe bleeding defect such as recurrent haemarthrosis and haematoma. The clinical features appear to improve with age. Both the PTT 'time course' and cold-induced EACA acceleration of the thromboplastin time are useful diagnostic tests for detecting homozygous patients. Our results confirm an earlier report that the EACA test is a sensitive test for detecting heterozygotes.
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PMID:Fletcher factor deficiency--detection of a severe case in a population survey. 41 13

The evaluation of excessive hemorrhage was carried out in 774 patients after cardiopulmonary bypass. Excessive hemorrhage was defined in any adult patient as chest tube drainage of more than 600 ml within the first eight hours after operation. Using the prothrombin time, partial thromboplastin time, fibrinogen level, and tri-F titer tests, it was possible to differentiate medical from surgical bleeding. Hyperfibrinolytic bleeding was the most frequently identifiable coagulation disorder and occurred in 159 patients (20%). All these patients were successfully treated with Amicar (epsilon-aminocaproic acid) alone, or with Amicar supplemented with cryoprecipitate or fresh-frozen plasma. Three patients (0.4%) were noted to have residual heparin and required additional protamine sulfate. Five patients (0.6%) had normal coagulation studies and required immediate reexploration. The overall blood consumption per patient was 2.1 units of packed cells. Whole blood and platelets were not used.
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PMID:The treatment of postperfusion bleeding using epsilon-aminocaproic acid, cryoprecipitate, fresh-frozen plasma, and protamine sulfate. 49 96

The kringle 2 (E161T/C162S/EEE[K2HPg/C169S]TT) and the kringle 3 (TYQ[K3HPg]DS) domains of human plasminogen (HPg) were expressed in Escherichia coli in an expression vector with the phage T5 promotor/operator element N250PSN250P29 and the cDNA sequence for a hexahistidine tail to facilitate the isolation of the recombinant protein. A coagulation factor Xa (FXa)-sensitive cleavage site was introduced to remove the N-terminal histidine tag. In r-K2, mutations E161T and C162S were introduced to enhance the FXa cleavage yield and C169S to replace the cysteine residue, participating in the inter-kringle disulfide bridge between kringles 2 and 3. Recombinant proteins were isolated by affinity chromatography on Ni(2+)-nitrilotriacetic acid/agarose and refolded under denaturing and reducing conditions followed by a non-denaturing and oxidising environment. The free thiol group in position 297 in r-K3 was selectively alkylated with iodoacetamide. The hexahistidine tail was successfully removed with FXa. The N-terminal sequence, the amino acid composition and the molecular mass analyses are in agreement with the expected data. The correct arrangement of the disulfide bonds was verified by sequence analysis of the corresponding thermolytic and subtilisin fragments. r-K2 exhibits weak binding to lysine-Bio-Gel. The weak binding affinity of r-K2 for omega-aminocarboxylic acids is confirmed by intrinsic fluorescence titration with 6-aminohexanoic acid (NH2C5COOH) indicating a Kd of approximately 401 microM. In contrast, r-K3 seems to be devoid of a binding affinity for omega-aminocarboxylic acids. Considering earlier determined Kd values of kringle 1, kringle 4 and kringle 5, the binding affinity of HPg kringle domains for NH2C5COOH is proposed to decrease in the following order, kringle 1 > kringle 4 > kringle 5 > kringle 2 > kringle 3.
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PMID:Expression, purification and characterization of the recombinant kringle 2 and kringle 3 domains of human plasminogen and analysis of their binding affinity for omega-aminocarboxylic acids. 830 12

Enoxaparin (Lovenox; Roule-Poulenc Rorer, Inc.), a low molecular weight heparin (LMWH), is commonly used in the management of non-ST-segment elevation acute coronary syndromes (NSTE ACS) based on clinical trial outcomes. It is one of a group of glycosaminoglycan compounds that accelerate the inactivation of factor Xa by inducing a conformational change in antithrombin. In contrast to unfractionated heparin (UFH), LMWH have greater bioavailability, a more predictable anticoagulant response, longer half-life and a higher proportion of anti-factor Xa to anti-factor IIa activity. As a consequence, laboratory monitoring of the anticoagulant effect is typically unnecessary. Antithrombin therapy with LMWH or UFH has the highest-level recommendation (IA) in the 2002 professional guidelines for the management of unstable angina and non-ST-elevation myocardial infarction, where enoxaparin has a IIA recommendation over UFH unless early coronary artery bypass surgery is planned. In a recent systematic overview of > 20,000 patients with NSTE ACS from six clinical trials, including conservative and invasively managed patients, enoxaparin provided a statistically significant reduction in 30-day death or nonfatal myocardial infarction (MI) compared with UFH with no significant excess in transfusions, or major bleeding. These data support the role of enoxaparin as an anti-coagulant in patients with NSTE ACS.
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PMID:Clinical use of enoxaparin in the management of non-ST segment elevation acute coronary syndromes. 1595 76

Fondaparinux sodium (Arixtra) is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor that is indicated in Europe for preventing thrombus formation in patients with acute coronary syndromes (ACS; the focus of this review), including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina.The large (n = 20,078), well designed OASIS-5 trial showed that subcutaneous fondaparinux 2.5 mg/day for <or=8 days was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (once daily in those with renal dysfunction) in reducing death or ischemic events at 9 days and the efficacy was maintained for up to 6 months (study end) in patients with unstable angina or NSTEMI. During this time, major bleeding occurred in fewer fondaparinux than enoxaparin recipients, resulting in a benefit: risk balance favoring fondaparinux. The incidence of death or reinfarction at 30 days was significantly lower in recipients of subcutaneous fondaparinux 2.5 mg/day than in those who received usual care (including unfractionated heparin [UFH] treatment as indicated) in patients with STEMI in the large (n > 12,000) OASIS-6 trial. There were no differences in the incidence of major bleeding between these groups, resulting in a benefit : risk balance favoring fondaparinux. The specificity and selectivity of fondaparinux, combined with its long half-life and 100% bioavailability, allows once-daily anticoagulation without the need for monitoring activated clotting time. Subcutaneous fondaparinux was noninferior to enoxaparin treatment in patients with unstable angina or NSTEMI, and was more effective than usual care in those with STEMI. Fondaparinux has a favorable tolerability profile, particularly with regard to the risk of major bleeding, and limited data suggest that it is more cost effective than enoxaparin in the short term. Thus, overall, clinical evidence suggests that fondaparinux has a valuable place in the treatment of patients with ACS.
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PMID:Fondaparinux sodium: a review of its use in the management of acute coronary syndromes. 1842 94

Management of venous thromboembolism disease could be improved by new drugs with lower risk of bleeding and without the need of regular monitoring of anticoagulant effect. In this way, idraparinux, anti-Xa inhibitor, has been compared to conventional therapy (coumarins) for the treatment of deep vein thrombosis and pulmonary embolism. Is it worth to treat patients more than six months? This has been evaluated in an interesting study. Prophylaxis after hip replacement surgery is indicated to reduce the risk of venous thromboembolism, new drugs are under investigation. Dabigatran etexilate, a direct thrombin inhibitor, has been shown as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery. In 2007, new european guidelines for non-STsegment elevation acute coronary syndromes have been published. Two new antithrombotic drugs, bivalirudin and fondaparinux, are now part of the different possible choices according to specific considerations. New factor Xa and factor IIa inhibitors are under investigation and are compared to heparin in PCI for NSTE-ACS. Fondaparinux and more recently otamixaban have given interesting results. These new recommendations have not yet taken into account new data published in 2007. What will be the positioning of prasugrel, a new thienopyridine, after the results of theTRITON trial? In patients with SCA treated by PCI, prasugrel reduced the ischemic events, while increasing major bleedings. In 2007, numerous publications and meta-analyses on drug-eluting stents (DES) have been published and tempered the fear about a possible increase in mortality with the use of DES.
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PMID:[What's new on antithrombotics?]. 1895 Jul 43

Fondaparinux sodium (Arixtra) is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor that is indicated in Europe for preventing thrombus formation in patients with acute coronary syndromes (ACS; the focus of this review), including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina. The large (n = 20,078), well designed OASIS-5 trial showed that subcutaneous fondaparinux 2.5 mg/day for < or =8 days was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (once daily in those with renal dysfunction) in reducing death or ischemic events at 9 days and the efficacy was maintained for up to 6 months (study end) in patients with unstable angina or NSTEMI. During this time, major bleeding occurred in fewer fondaparinux than enoxaparin recipients, resulting in a benefit : risk balance favoring fondaparinux. The incidence of death or reinfarction at 30 days was significantly lower in recipients of subcutaneous fondaparinux 2.5 mg/day than in those who received usual care (including unfractionated heparin treatment as indicated) in patients with STEMI in the large (n > 12,000) OASIS-6 trial. There were no differences in the incidence of major bleeding between these groups, resulting in a benefit : risk balance favoring fondaparinux. The specificity and selectivity of fondaparinux, combined with its long half-life and 100% bioavailability, allows once-daily anticoagulation without the need for monitoring activated clotting time. Subcutaneous fondaparinux was noninferior to enoxaparin treatment in patients with unstable angina or NSTEMI, and was more effective than usual care in those with STEMI. Fondaparinux has a favorable tolerability profile, particularly with regard to the risk of major bleeding, and limited data suggest that it is more cost effective than enoxaparin in the short term. Thus, overall, clinical evidence suggests that fondaparinux has a valuable place in the treatment of patients with ACS.
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PMID:Spotlight on fondaparinux sodium in acute coronary syndromes. 1899 58

The biocompatibility of iron-polysaccharide complexes has been well-documented. Herein, a stable thrombo-resistant coating was fabricated by consecutive adsorption of Fe (III) and polysaccharides including heparin (Hep) and dextran sulfate (DS) onto various surface by layer-by-layer self-assembly technique via both electrostatic interaction and chemical complexation process. The absorbance at 350 nm increased linearly with the number of Fe3+/Hep multilayer, indicating the formation of multilayer structure and the uniform coating. Compared with (Fe3+/Hep)10, the (Fe3+/DS/Fe3+/Hep)5 coating was more hydrophilic and stable due to the incorporation of DS. The activated partial thromboplastin time (APTT) and platelet adhesion assays showed that both (Fe3+/Hep)10 and (Fe3+/DS/Fe3+/Hep)5 coated surfaces were anticoagulant. The complexing with ferric ions did not compromise the catalytic capacity of heparin to promote antithrombin(III)-mediated thrombin inactivation. Chromogenic assays for heparin activity proved definitively that the inhibition of locally produced thrombin was contributed to the thromboresistance of the surface-bound heparin. The surface with Hep or DS as the outmost layer showed stronger anticoagulant activity than Fe3+, indicating that the outermost layer of the coating played a key role in anticoagulant activity. The utilization of dextran sulfate/heparin surfaces was more advantageous than merely the heparin surface for improving blood-contacting medical devices for long-term usage.
ACS Appl Mater Interfaces 2009 Jan
PMID:Novel thrombo-resistant coating based on iron-polysaccharide complex multilayers. 2035 62

Fondaparinux (Arixtra) is an anticoagulant that selectively inhibits activated factor X, thereby interrupting the blood coagulation cascade. In OASIS-5, a large pivotal trial in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), subcutaneous fondaparinux 2.5 mg once daily was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (both agents were administered over a mean of about 5 days in combination with antiplatelet therapy) in reducing death or ischaemic events at 9 days, and the efficacy was maintained for up to 6 months (study end). However, fondaparinux was associated with a significantly lower rate of bleeding than enoxaparin in the first 9 days, and at 3 and 6 months. This lower rate of bleeding led to lower long-term mortality and morbidity with fondaparinux than with enoxaparin. In modelled cost-utility analyses conducted from a healthcare payer perspective in Spain, France and the US with a lifetime horizon, fondaparinux once daily was predicted to be cost effective relative to enoxaparin twice daily with regard to the incremental cost per QALY gained. In Spain and the US, fondaparinux dominated enoxaparin (i.e. was less costly and more effective) and, in the French analysis, the incremental cost per QALY gained with fondaparinux versus enoxaparin was well within recommended thresholds. Results of short-term (6-month) cost analyses in the US and France also favoured fondaparinux over enoxaparin. Sensitivity analyses demonstrated that base-case conclusions were robust over a range of parameter estimates and assumptions, including plausible variations in baseline risk of a cardiac event or baseline risk of bleeding. In conclusion, in patients with NSTE-ACS receiving antiplatelet therapy, fondaparinux was cost effective relative to enoxaparin in cost-utility analyses in Europe and the US. This cost advantage primarily reflects the lower rate of bleeding with fondaparinux than with enoxaparin and the lower rate of mortality and morbidity over the long term.
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PMID:Fondaparinux: a pharmacoeconomic review of its use in the management of non-ST-segment elevation acute coronary syndrome. 2061 58

A phosphorylcholine-like silane coupling agent bearing zwitterionic molecular structure was synthesized and studied. The chemical structure of this silane coupling agent was characterized by FTIR, 1H NMR and 31P NMR. The zwitterionic structure was successfully constructed onto the surface of silicon as a self-assembled layer (SAL). Static water contact angle, and atomic force microscopy (AFM) were used to investigate the wettability and surface topography of the modified silicon surfaces. Static water contact angle results indicated that the hydrophilicity of the surfaces could be effectively improved by the modification with this zwitterionic silane coupling agent. The changes of the topography and water contact angle of the modified surfaces with different incubation periods in PBS solution were also measured to evaluate the stability of the SALs. Blood compatibility of the modified surfaces were evaluated by testing the full-blood activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT), as well as by observing the adhered blood platelets onto the surface. The modified surfaces showed prolonged clotting time and fewer adherent platelets, revealing that the blood compatibility was evidently improved by the modification using this zwitterionic silane.
ACS Appl Mater Interfaces 2010 Oct
PMID:Synthesis of a zwitterionic silane and its application in the surface modification of silicon-based material surfaces for improved hemocompatibility. 2083 2


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