scholarly journals Antithrombotics and new interventions for venous thromboembolism: Exploring possibilities beyond factor IIa and factor Xa inhibition

2021 ◽  
Vol 5 (4) ◽  
Author(s):  
Anna C. Mavromanoli ◽  
Stefano Barco ◽  
Stavros V. Konstantinides
Keyword(s):  
Venous Thromboembolism ◽  
Factor Xa ◽  
Factor Xa Inhibition

Long Acting Anticoagulant Effects of Idraparinux in Patients Treated for Prophylaxis of Recurrent Venous Thromboembolism.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 899-899
Author(s):  
Job Harenberg ◽  
Ingrid Joerg ◽  
Christel Weiss ◽  
Tivadar Fenyvesi
Keyword(s):  
Venous Thromboembolism ◽  
Half Life ◽  
Factor Xa ◽  
Extension Study ◽  
Assay Method ◽  
Fixed Dose ◽  
Pharmacokinetic Analysis ◽  
Therapy Termination ◽  
Recurrent Venous Thromboembolism ◽  
Factor Xa Inhibition

Abstract Prophylaxis of recurrent venous thromboembolism (VTE) has been investigated in patients with acute VTE participating in the VanGogh DVT, PE and Extension studies for a minimum of 6 months. These patients were given a fixed dose of Idraparinux once a week subcutaneously without coagulation monitoring. The VanGogh DVT/PE studies randomized patients to Idraparinux versus INR-adjusted Warfarin. Patients were then able to follow on to the double-blind VanGogh Extension study comparing Idraparinux versus placebo. Determination of the anticoagulant effects may still be necessary for patients in acute clinical settings. After termination of the studies, the anticoagulant effects of Idraparinux were followed-up in 23 patients using Heptest coagulation method, anti-factor Xa inhibition method (aXa, chromogenic substrate S2222) and prothrombin induced clotting time (PiCT) assay. The study was accepted by the local ethics board and patients gave written informed consent. Serial blood samples were taken for up to 15 months after termination. The Heptest and PiCT methods were prolonged in all patients’ blood for 9 to 15 months after therapy termination. The chromogenic assay method showed factor-Xa inhibition for the same period of follow-up. The elimination half-life of Idraparinux was calculated at 60.5 ± 23.3 days using the Heptest method and at 55.1±15.4 days using the aXa-assay method. There were no differences noted in the half-life between patients participating in the DVT/PE and Extension study. The half-lives were independent from patients’ body weight and creatinine clearance. The complete pharmacokinetic analysis of the results will be presented. The unexpectedly long half-life may be explained by the lipophilicity of methylated Idraparinux. Overall, the data suggests a benefit from the prolonged antithrombotic effect of Idraparinux as well as an increased risk of hemorrhage after therapy termination, possibly explaining some of the van Gogh studies results.

Factor Xa inhibition in the prevention of venous thromboembolism and treatment of patients with venous thromboembolism

2002 ◽  
Vol 8 (5) ◽  
pp. 398-404 ◽  
Author(s):  
Kenneth A. Bauer ◽  
Bengt I. Eriksson ◽  
Michael R. Lassen ◽  
Alexander G.G. Turpie
Keyword(s):  
Venous Thromboembolism ◽  
Factor Xa ◽  
Factor Xa Inhibition

Treatment and secondary prevention of venous thromboembolism in cancer patients

2012 ◽  
Vol 03 (03) ◽  
pp. 121-125
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

Effect of Depolymerized Holothurian Glycosaminoglycan (DHG) on Tissue Factor Pathway Inhibitor: In Vitro and In Vivo Studies

1997 ◽  
Vol 78 (02) ◽  
pp. 864-870 ◽  
Author(s):  
Hideki Nagase ◽  
Kei-ichi Enjyoji ◽  
Yu-ichi Kamikubo ◽  
Keiko T Kitazato ◽  
Kenji Kitazato ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Factor Xa ◽  
Free Form ◽  
Initial Reaction ◽  
Extrinsic Pathway ◽  
Factor Xa Inhibition ◽  
Tissue Factor Pathway

SummaryDepolymerized holothurian glycosaminoglycan (DHG) is a glycosaminoglycan extracted from the sea cucumber Stichopus japonicusSelenka. In previous studies, we demonstrated that DHG has antithrombotic and anticoagulant activities that are distinguishable from those of heparin and dermatan sulfate. In the present study, we examined the effect of DHG on the tissue factor pathway inhibitor (TFPI), which inhibits the initial reaction of the tissue factor (TF)-mediated coagulation pathway. We first examined the effect of DHG on factor Xa inhibition by TFPI and the inhibition of TF-factor Vila by TFPI-factor Xa in in vitro experiments using human purified proteins. DHG increased the rate of factor Xa inhibition by TFPI, which was abolished either with a synthetic C-terminal peptide or with a synthetic K3 domain peptide of TFPI. In contrast, DHG reduced the rate of TF-factor Vila inhibition by TFPI-factor Xa. Therefore, the effect of DHG on in vitroactivity of TFPI appears to be contradictory. We then examined the effect of DHG on TFPI in cynomolgus monkeys and compared it with that of unfractionated heparin. DHG induced an increase in the circulating level of free-form TFPI in plasma about 20-fold when administered i.v. at 1 mg/kg. The prothrombin time (PT) in monkey plasma after DHG administration was longer than that estimated from the plasma concentrations of DHG. Therefore, free-form TFPI released by DHG seems to play an additive role in the anticoagulant mechanisms of DHG through the extrinsic pathway in vivo. From the results shown in the present work and in previous studies, we conclude that DHG shows anticoagulant activity at various stages of coagulation reactions, i.e., by inhibiting the initial reaction of the extrinsic pathway, by inhibiting the intrinsic Xase, and by inhibiting thrombin.

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