The Cheno Cooperative Study: Its Meaning for Gallstone Treatment

Abstract

Novel oral anticoagulants (OACs), including dabigatran etexilate, rivaroxaban, and apixaban, are available alternative anticoagulant therapy to vitamin K antagonists. The US Food and Drug Administration (FDA) has approved dabigatran, rivaroxaban, and apixaban for the treatment of appropriate patients for specific clinical indications. Therapeutic advantages of prescribing the new OACs are related to their predictable pharmacokinetic and pharmacodynamic properties. Dabigatran, rivaroxaban, and apixaban have all been shown to be noninferior to warfarin treatment for stroke prevention in respective phase 3 clinical trials; dabigatran and apixaban were shown to be superior to warfarin as preventive therapy. Dabigatran, rivaroxaban, and apixaban are all approved agents for stroke prevention in patients with nonvalvular atrial fibrillation in the United States and Europe. Among these agents, rivaroxaban is the only FDA-approved drug for the treatment of venous thromboembolism. This article reviews the major clinical trials that investigated the efficacy and safety of the new OACs and the use of these agents in special clinical situations.     

达比加群对凝血酶诱导的人气道平滑肌细胞收缩和增殖的影响

目的 探讨这比加群对凝血酶诱导的人气道平滑肌(HASM)细胞收缩和增殖的影响.方法 将原代培养的HASM细胞用于实验.用免疫荧光的方法观察细胞收缩的形态学变化;用Western blot法分析α-actin蛋白相对表达量;用cck8法检测平滑肌细胞增殖能力.结果 达比加群能显著抑制凝血酶诱导的HASM细胞骨架重组和收缩蛋白α-actin的表达(P＜0.05).对血管紧张素Ⅱ(AngⅡ)、转化生长因子-β1、血小板源性生长因子、乙酰甲胆碱、凝血酶的促增殖能力进行比较,凝血酶显著强于AngⅡ,仅次于10％胎牛血清(P＜0.05).达比加群呈浓度依赖性和时间依赖性地抑制了凝血酶诱导的HASM细胞增殖(P＜0.05).结论 达比加群能够显著抑制凝血酶诱导的HASM细胞收缩和增殖.     

The fibrinogen prothrombin time‐derived method is not useful in patients anticoagulated with low molecular weight heparins or rivaroxaban

Essentials

• Fibrinogen prothrombin time‐derived (FIBPT‐d) behavior in anticoagulated patients is under studied.
• FIBPT‐d method overestimates fibrinogen in rivaroxaban and low molecular weight heparin samples.
• Unfractionated heparin and dabigatran samples showed similar bias to the control group.
• Rabbit brain and human recombinant thromboplastin behavior was different in rivaroxaban samples.

Summary

Background

The fibrinogen prothrombin time‐derived (FIBPT‐d) method with photo‐optical coagulometers is easy and economical. However, there are few reports on the behavior of this test on samples from patients anticoagulated with direct oral anticoagulants or low molecular weight heparin (LMWH).

Objective

To compare fibrinogen results obtained with the Clauss (FIB C) method and the FIBPT‐d method with two thromboplastins in anticoagulated patients.

Population

The study population comprised 295 consecutive anticoagulated patients: 99 treated with vitamin K antagonists (VKAs), 49 treated with unfractionated heparin (UFH), 47 treated with LMWH, 50 treated with rivaroxaban, 50 treated with dabigatran, and 100 normal controls (NCs).

Methods

Dabigatran samples were analyzed by the use of FIB C with HemosIL Fibrinogen C or 100 NHI thrombin units mL^?1 reagents; rabbit brain and human recombinant thromboplastins with HemosIL PTFibrinogen HS plus (HS) and Recombiplastin 2G (RP) were used for FIBPT‐d method. Heparin and rivaroxaban levels were assessed with HemosIL Liq antiXa with specific calibrators; dabigatran levels were determined with the HemosIL Direct Thrombin Inhibitor Assay. All assays were performed on the ACL TOP platform in two laboratories. Percentage biases for the FIBPT‐d method versus the FIB C method were calculated by the use of Bland–Altman plots.

Results

Positive biases of the FIBPT‐d method versus the FIB C method with both thromboplastins were seen in NC samples (13.7% and 18.9% for HS and RP, respectively), but biases with HS in rivaroxaban and VKA patient samples were higher than that in NC samples, at 31.9% and 34.0%, respectively. LMWH patient samples showed higher bias than NC samples: 26.5% and 29.3.0% with HS and RP, respectively. UFH and dabigatran patient samples showed similar bias as NC samples.

Conclusion

The FIBPT‐d method should not be used in anticoagulated patients, because the FIBPT‐d mathematical algorithm has been validated only in normal subjects, so overestimation could occur in these patients.

     

Healthcare burden associated with the post-thrombotic syndrome and potential impact of the new oral anticoagulants

Deep-vein thrombosis (DVT) can have a significant impact on a patient's life. In particular, the development of post-thrombotic syndrome as a long-term complication of DVT can have devastating consequences for the individual and impose a substantial economic burden on healthcare systems. Anticoagulants are the mainstay of DVT treatment; however, the current standard of care, a parenteral anticoagulant followed by a vitamin K antagonist, is associated with complex patient management, often resulting in suboptimal therapy. New, oral anticoagulants have been developed, and a direct thrombin inhibitor--dabigatran etexilate--and two direct Factor Xa inhibitors--rivaroxaban and apixaban--have completed and/or have ongoing phase III trials in the treatment of venous thromboembolism. These agents do not have the drawbacks of the vitamin K antagonists and hold promise for more effective treatment of DVT, possibly resulting in a reduction in the incidence of post-thrombotic syndrome.     

房颤合并肝硬化患者的口服抗凝药物选择及抗栓策略研究

目的 探讨房颤合并肝硬化患者临床治疗中口服抗凝药物的选择及安全性。方法 在1例房颤合并乙型肝炎肝硬化患者房间隔修补术后抗栓方案的制定中,通过查阅指南和文献,总结、分析房颤合并肝硬化患者口服抗凝药物的疗效及安全性评价现状。结果 通过综合评估患者情况,停用华法林,予达比加群酯110 mg,bid,联合氯吡格雷75 mg,qd抗栓6个月,之后达比加群酯110 mg,bid长期抗凝治疗。结论 房颤合并肝硬化患者抗栓治疗,应充分评估血栓及出血风险,制定个体化的抗栓策略。房颤合并Child-Pugh A级肝硬化,新型口服抗凝药均可使用;合并Child-Pugh C级肝硬化,口服抗凝剂均不建议使用;合并Child-Pugh B级肝硬化,出血风险高的患者长期抗凝治疗中可选用小剂量达比加群酯。