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Direct Factor (direct + factor)

Distribution by Scientific Domains
Medical Sciences100%

Terms modified by Direct Factor

  • direct factor xa inhibitor
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    Selected Abstracts

    Initial experience with factor-Xa inhibition in percutaneous coronary intervention: the XaNADU-PCI Pilot

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2004
    J. H. Alexander
    Summary.,Background:,Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI). Objectives:,To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX-9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI. Patients and methods:,Patients undergoing elective, native-vessel PCI (n = 175) were randomized 4 : 1 to open-label DX-9065a or heparin in one of four sequential stages. DX-9065a regimens in stages I,III were designed to achieve concentrations of >,100 ng mL,1, >,75 ng mL,1, and >,150 ng mL,1. Stage IV used the stage III regimen but included patients recently given heparin. Results:,At 15 min median (minimum) DX-9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL,1 in stages I,IV, respectively. Median whole-blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti-FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL,1, respectively. Stage II enrollment was stopped (n = 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX-9065a dose. Conclusions:,Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double-bolus and infusion DX-9065a dosing. Monitoring of DX-9065a may be possible using whole-blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study. [source]

    A multi center study of granulocyte and monocyte adsorption apheresis therapy for ulcerative colitis,Clinical efficacy and production of interleukin-1 receptor antagonist

    JOURNAL OF CLINICAL APHERESIS, Issue 3 2008
    Hiroaki Takeda
    Abstract Granulocyte and monocyte adsorption apheresis (GCAP) is a useful strategy for intractable ulcerative colitis, but its mechanisms of therapy is not fully explained. Previously, depleting activated granulocytes and monocytes (GMs) and modifying product of proinflammatory cytokines had been proposed. In addition, activated GMs are releasing anti-inflammatory cytokines, interleukin-1 receptor antagonist (IL-1ra) that may contribute to the clinical efficacy of GCAP therapy. Hence, to investigate contribution of IL-1ra as well as to confirm clinical efficacy of this therapy based on clinical activity index (CAI), we performed a multicenter study. Twenty-five of 38 (65.8%) patients achieved remission state (CAI , 4) and two of 38 (5.3%) revealed clinical improvement. Almost effective cases significantly decreased CAI even at 3rd session of GCAP. Plasma level of IL-1ra from outflow of the GCAP column at 30 min was significantly increased rather than inflow. Median exact elevated level of IL-1ra was 221 pg/ml and median of increasing ratio was 1.6 times. Furthermore, the responsive patients, who well released the IL-1ra at outflow more than 100 pg/ml compared with inflow, tended to show clinical effectiveness. While, the increased ratio of IL-1ra in effective cases did not differ from ineffective cases, and there were no significant relationship with improvement of CAI score. These conflict results suggest that the increase of IL-1ra at outflow is not a direct factor to the clinical improvement, but the induction of clinical improvement is accompanied by the release of IL-1ra. The IL-1ra may be involved in the multiple steps for the improvement induced by GCAP. J. Clin. Apheresis, 2008. © 2008 Wiley-Liss, Inc. [source]

    Factor Xa or thrombin: is factor Xa a better target?

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2007
    J. ANSELL
    Summary., Existing vitamin K antagonists (VKAs) have drawbacks that limit their effectiveness, safety, and overall frequency of use. Oral anticoagulants in development with targeted action against individual coagulation factors, specifically direct factor (F) Xa and IIa inhibitors, appear to have pharmacokinetic and pharmacodynamic properties that overcome the limitations of the VKAs. Based on the theory of how coagulation factors interact, on the results of in vitro studies, and on clinical outcomes, there is accumulating evidence that FXa may represent a better target for inhibition than FIIa. This is based on an understanding of the amplified nature of coagulation factor interactions and fibrin formation, the need for smaller doses of an anticoagulant to block coagulation progression earlier in the sequence of reactions, the evidence for incomplete suppression of thrombin generation with direct thrombin inhibitors, evidence for rebound hypercoagulability with thrombin inhibitors, and clinical results with the indirect, parenteral, FXa inhibitor (fondaparinux), as well as early phase II results of new oral Xa and IIa inhibitors compared with enoxaparin. The latter studies, although not comparative, provide some evidence for the effectiveness and safety of Xa inhibitors at a range of doses not seen with the direct IIa inhibitors. [source]

    Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibition

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2004
    K. KARNICKI
    Summary.,Background/objective: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. Methods: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 µg kg,1 bolus +,1.5 µg kg,1 min,1 infusion, n = 6); ZK-807834-Dose 2 (20 µg kg,1 bolus +,0.75 µg kg,1 min,1 infusion; n = 6); enoxaparin (1 mg kg,1 bolus; n = 6); or saline (n = 6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. Results: The prothrombin time ratio was 2.2 ± 0.1; 1.4 ± 0.3; 1.2 ± 0.9 and 1.1 ± 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 ± 226 × 106 cm,2; P = 0.008), whereas ZK-807834-Dose 2 (2325 ± 768) and enoxaparin (1236 ± 383) were not different from saline (2776 ± 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 ± 185). Neither ZK-807834-Dose 2 (1588 ± 480) nor enoxaparin (1618 ± 686) was different from saline control (2222 ± 598). Conclusions: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective. [source]