Oral Direct Thrombin Inhibitors and Oral Factor Xa Inhibitors

2012 ◽  
pp. 180-188
Author(s):  
Steen Husted ◽  
Lars Wallentin
Keyword(s):  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Direct Thrombin Inhibitors

Direct Thrombin Inhibitors and Factor Xa Inhibitors Can Influence the Diluted Prothrombin Time Used as the Initial Screen for Lupus Anticoagulant

2013 ◽  
Vol 137 (7) ◽  
pp. 967-973 ◽  
Author(s):  
Zsolt Olah ◽  
Mariann Szarvas ◽  
Zsuzsanna Bereczky ◽  
Adrienne Kerenyi ◽  
Janos Kappelmayer ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Lupus Anticoagulant ◽  
Factor Xa ◽  
Linear Increase ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
False Positivity ◽  
Before And After ◽  
Confirmatory Tests

Context.—Lupus anticoagulant (LA) is a heterogeneous group of antiphospholipid antibodies. Among others, diluted prothrombin time (dPT) is a sensitive screening test for LA; however, the interpretation of LA tests is difficult in patients treated with anticoagulants. The effect of different types of anticoagulants on the result of LA tests, particularly on dPT, has not been studied extensively. Objective.—To determine whether the direct thrombin inhibitors lepirudin and argatroban and the predominantly factor Xa inhibitors enoxaparin, danaparoid, and fondaparinux could interfere with LA screening based on dPT. Design.—Each drug was added to normal and LA-positive plasmas in clinically relevant concentrations. Each sample was tested for dPT. Samples with factor Xa inhibitors were investigated before and after addition of heparinase. Mixing and confirmatory tests for LA were not performed. Results.—In the presence of lepirudin or argatroban, dPT increased notably and the dPT ratio exceeded the cutoff value even at subtherapeutic concentrations resulting in false positivity. With increasing factor Xa inhibitor concentrations, a linear increase of dPT ratios and false-positive results were also demonstrated. Although heparinase could almost completely neutralize the anti-Xa effect of all investigated factor Xa inhibitors, dPT ratio returned to the basal level only in case of enoxaparin. Conclusions.—Here we provide evidence that both the direct thrombin and indirect factor Xa inhibitors influence dPT assay for LA, causing false positivity. This should be considered when interpreting LA results during anticoagulant therapy. However, dPT seems to be a reliable test for LA screening under enoxaparin therapy after neutralization by heparinase.

Effects of Dabigatran, a Direct Thrombin Inhibitor, as Compared to the Direct Factor Xa Inhibitors, Rivaroxaban and Apixaban, on Tissue Factor-Induced Human Platelet Aggregation in Platelet Rich Plasma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1884-1884 ◽  
Author(s):  
Joanne van Ryn ◽  
Monika Kink-Eiband ◽  
Norbert Hauel ◽  
Henning Priepke ◽  
Wolfgang Wienen
Keyword(s):  
Platelet Aggregation ◽  
Tissue Factor ◽  
Potent Inhibitor ◽  
Platelet Rich Plasma ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Direct Factor ◽  
Direct Factor Xa Inhibitors

Abstract Direct thrombin inhibitors (DTIs) have been shown to be very potent inhibitors of platelet function when platelets are activated with thrombin. This action does not occur by direct binding of the DTI to the platelet PAR-1/-4 receptor, but indirectly, by reducing thrombin concentrations and thereby reducing the interactions of thrombin with its receptor on the platelet. It was hypothesized that both thrombin and factor Xa inhibitors could inhibit platelet aggregation, if the stimulus to initiate aggregation was higher in the cascade than factor Xa, such as tissue factor. Thus, dabigatran, a DTI, and the direct factor Xa inhibitors, rivaroxaban and apixaban were tested. Free flowing whole blood (60 ml) was obtained from an antecubital vein using an 18 gauge needle from healthy human volunteers. Blood was collected in tubes containing 3.13% sodium citrate (1 in 10 dilution with whole blood). Blood was centrifuged at 200x g to obtain platelet rich plasma (PRP). Samples (300 μL PRP) were placed in a 6-channel aggregometer, equilibrated for 5 min at 37°C and calibrated with PPP from same individual (0–1 Volts). Photometric tracings were continuously digitally recorded over 5 min following the addition of tissue factor and curves were evaluated as AUC over this time interval. Each PRP sample was incubated with 2 mg/ml Pefabloc®FG (Gly-Pro-Arg-Pro) to prevent fibrin polymerisation, 5 mM CaCl2 and increasing concentrations of dabigatran or factor Xa inhibitor. Tissue factor stimulus (range, 5–27 μl of 10 ml Innovin solution) was tailored for each individual, so that the minimum concentration that resulted in maximum aggregation was used. As positive controls, aggregation was also performed after stimulating with ADP (10 μM), collagen (2 μg/ml), TRAP (20 μM) or ecarin (0.1 U/ml). All substances inhibited tissue factor-induced platelet aggregation in a concentration-dependent manner. Dabigatran was the most potent inhibitor of platelet aggregation among the substances tested, with an IC50 of 35 nM, rivaroxaban and then apixaban followed, with IC50s of 312 and 817 nM, respectively. All substances had no effect on platelet aggregation induced by ADP, collagen and TRAP. Dabigatran was a potent inhibitor of ecarin-induced platelet aggregation, while the factor Xa inhibitors had no effect, as expected from their mechanism of action. Thus, these studies demonstrate that both direct thrombin inhibitors (by inhibiting thrombin) and direct factor Xa inhibitors (by preventing thrombin generation) indirectly inhibit platelet aggregation, though dabigatran was more potent than rivaroxaban and apixaban under these experimental conditions. Thus, these substances may not only be effective in venous/stasis thrombotic episodes where fibrin formation plays an important role, but may also be effective in more platelet dominant, arterial thrombosis settings.

Direct thrombin inhibitors and factor Xa inhibitors in patients with cerebrovascular disease

2012 ◽  
Vol 12 (2) ◽  
pp. 179-190 ◽  
Author(s):  
Sarkis Morales-Vidal ◽  
Michael J Schneck ◽  
Murray Flaster ◽  
José Biller
Keyword(s):  
Cerebrovascular Disease ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Direct Thrombin Inhibitors

Global research status and trends in venous thromboembolism after hip or knee arthroplasty from 1990 to 2021: a new perspective (Preprint)

2021 ◽  
Author(s):  
Wei Song ◽  
Tao Ma ◽  
Qianyue Cheng ◽  
Pengfei Wen ◽  
Qiuyuan Wang ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Knee Arthroplasty ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Research Status ◽  
The Past ◽  
Oral Agents ◽  
Global Research

BACKGROUND Venous thromboembolism (VTE) after hip or knee arthroplasty has attracted increasing attention over the past few decades. However, there is no bibliometric report on the publications in this field. OBJECTIVE The purpose of this study was to analyze the global research status, hotspots, and trends in VTE after arthroplasty. METHODS All articles about VTE research after hip or knee arthroplasty from 1990 to 2021 were retrieved from the Web of Science Core Collection database. The information of each article including citation, title, author, journal, country, institution, and keywords, was extracted for bibliometric analysis. RESULTS A total of 1,245 original articles from 53 countries and 603 institutions were retrieved. The number of publications showed a rising trend, with the largest contributions made by the USA. McMaster University in Canada was the leading institution for publications. The most productive author in this field was Eriksson BI, followed by Lassen MR and Dahl OE. The journals with the highest output and highest citation were the Journal of Arthroplasty and the Thrombosis and Haemostasis, respectively. The research hotspots switched from VTE diagnosis and heparin to factor Xa inhibitors (fondaparinux, rivaroxaban, apixaban) and direct thrombin inhibitors (dabigatran etexilate, ximelagatran), and finally to aspirin, risk factor studies, which can be observed from the keyword analysis and co-cited reference cluster analysis. CONCLUSIONS Over the past few decades, the understanding of VTE after hip or knee arthroplasty has been improved significantly. VTE prophylaxis agents have attracted tremendous attention, including warfarin, low molecular weight heparin, oral direct factor Xa inhibitors, oral direct thrombin inhibitors, and aspirin. These studies exert a critical influence on decision-making and management for VTE. Additionally, individualized VTE prevention based on risk factors for each patient and the development of new safe, effective, and inexpensive oral agents will be emerging trends in the future.

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