Successful anticoagulation with bivalirudin in antithrombin-deficient pediatric patient undergoing stent placement.

Many pediatric patients requiring anticoagulation during interventional heart catheterizations have antithrombin (AT) deficiency. AT is a necessary cofactor for heparin inhibition of thrombin. Without sufficient AT, these patients are at increased risk for thrombotic complications. This case describes the successful use of bivalirudin, a direct thrombin inhibitor, as an anticoagulant in a 2-month old infant with AT deficiency undergoing stent placement.     

Direct thrombin inhibitors in cardiac disease

Most acute coronary syndromes (ACS) are triggered by platelet-rich thrombus superimposed on disrupted atherosclerotic plaque. Thrombin and platelets both play a role in this process. Whereas unfractionated heparin and aspirin have served as cornerstones in the treatment of ACS, several limitations of heparin provide the impetus to seek out better anticoagulants. Direct thrombin inhibitors such as bivalirudin, hirudin, and argatroban offer several pharmacologic advantages over heparin. Additionally, bivalirudin also appears to provide clinical advantages over unfractionated heparin therapy in ACS patients and those undergoing percutaneous coronary intervention.     

Bivalirudin or Heparin in Patients Undergoing Invasive Management of Acute Coronary Syndromes

Background

Contrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs).

Direct thrombin inhibitors

Heparins and vitamin K antagonists have been the primary agents used for anticoagulation in certain cardiovascular and thromboembolic diseases for over 50 years. However, they can be difficult to administer and are fraught with limitations. In response to the need for new anticoagulants, direct thrombin inhibitors (DTIs) have been developed and investigated for their utility in prophylaxis and treatment of venous thromboembolism (VTE), heparin-induced thrombocytopenia (HIT), acute coronary syndromes (ACS), secondary prevention of coronary events after ACS, and nonvalvular atrial fibrillation. Currently, four parenteral direct inhibitors of thrombin activity are FDA-approved in North America: lepirudin, desirudin, bivalirudin and argatroban. Of the new oral DTIs, dabigatran etexilate is the most studied and promising of these agents. This review discusses the clinical indications and efficacy of these direct thrombin inhibitors as well as future directions in anticoagulant therapy.     

固相合成抗凝血药比伐卢定及合成条件的优化

目的:研究使用Wang树脂与Fmoc保护策略固相合成抗凝血药比伐卢定(bivalirudin)的实验方法?方法:比伐卢定的合成经过了逐步偶联?TFA裂解?脱保护?HPLC纯化等一系列步骤?为了优化反应条件,选择了不同氨基酸取代度的树脂(0.29?0.48?0.59 mmol/g)和不同的缩合试剂(HBTU?DCC?HATU)进行试验?结果:成功得到了纯度为98%的比伐卢定?活性测定表明,不同方法合成的比伐卢定均具有与标准样品相当的抗凝活性,并且显示:①氨基酸取代度为0.3~0.4 mmol/g的Wang树脂可以得到产率及纯度均较高的产品,取代度太大(>0.5 mmol/g)得到的产品副产物多?纯度低;②用HBTU/HOBt为缩合试剂具有操作方便?成本经济?合成效率高等优点?根据以上实验结果选择优化条件,用5 g Wang树脂合成克级单位的比伐卢定,得到的粗品产率可达84%,纯度可达68%以上?结论:通过固相合成的方法,考察了不同氨基酸取代度?不同缩合试剂及规模大小对合成比伐卢定的产率?纯度及活性的影响,对比伐卢定的大量合成具有一定的指导作用?     

比伐卢定在高龄经皮冠脉介入治疗急性冠脉综合征患者中的疗效及安全性观察

目的 探讨高龄急性冠状动脉综合征（ACS）患者行经皮冠状动脉介入治疗（PCI）应用比伐卢定抗凝的疗效及安全性.方法 拟行PCI的年龄≥80岁ACS患者155例,随机分为比伐卢定组（78例）及普通肝素组（77例）.比较两组PCI术后24 h、30 d的主要心脑不良事件（MACCE）及出血发生率.结果 两组患者PCI术后24 h、30 d的MACCE发生率差异均无统计学意义（P〉0.05）.比伐卢定组患者术后出血发生率明显低于普通肝素组（P〈0.001）.结论 与普通肝素相比,比伐卢定在老年ACS接受PCI治疗的人群中,明显减少出血事件,且未增加MACCE发生率.     

Novel uses for current and future direct thrombin inhibitors: focus on ximelagatran and bivalirudin

Ximelagatran and bivalirudin are direct thrombin inhibitors that have been studied for the prevention and treatment of thrombosis and have potential advantages over the traditional indirect thrombin inhibitors (i.e., warfarin, unfractionated heparin and low molecular-weight heparin). They are both reversible inhibitors of thrombin and block both circulating and fibrin-bound thrombin. Ximelagatran and bivalirudin possess favourable pharmacokinetic and pharmacodynamic profiles including wider therapeutic indices, faster onsets of action and less interpatient variability compared to indirect thrombin inhibitors. Ximelagatran has shown favourable clinical trial results in venous thromboembolism prophylaxis and atrial fibrillation. Similarly, bivalirudin has shown positive results in patients with acute coronary syndromes, however, further investigation is needed. Ximelagatran and bivalirudin have shown promising results in the management of thrombosis and the results of future studies confirming their use for the aforementioned indications are anticipated.