Rivaroxabán en síndrome antifosfolipídico tras fracaso con acenocumarol: a propósito de 2 casos

Antiphospholipid syndrome is characterized by abortions or thrombotic phenomena associated with specific antibodies. Anticoagulant therapy is based on vitamin K antagonists. We present two cases in which the use of rivaroxaban achieved control of the disease after the failure of acenocoumarol.     

Thrombin Generation in a patient with Triple Positive Antiphospholipid Syndrome Treated with Three Different Anticoagulants

IntroductionVenous and arterial thrombosis is one of the hallmarks of Antiphospholipid Antibody Syndrome (APS). The traditional treatment for individuals with APS and venous thrombosis has been vitamin K antagonists. However, with the widespread use of direct oral anticoagulants (DOACs) there has been conflicting evidence regarding their safety and failure rate as alternatives to warfarin. Reasons for this failure remain elusive. We utilized the thrombin generation assay (TGA) to investigate the anticoagulation efficacy of three different agents in a patient with triple-positive APS to acquire a better understanding of the pathophysiology of APS.MethodsBlood samples were obtained from a single patient with APS at five distinct time points while on three different anticoagulants: rivaroxaban, warfarin, and enoxaparin. The effects of these anticoagulants on TG potential were evaluated using the TGA.ResultsIn the presence of thrombomodulin, rivaroxaban had the highest endogenous thrombin potential, thrombin peak, velocity index, and thrombin inactivation velocity (821.9 nMmin, 121.5 nM, 36.44 nM/min, 7.19 nM/min) when compared to warfarin (121-367 nMmin, 13.85-121.5 nM, 3.02-3.85 nM/min, 0.64-4.55 nM/min) and enoxaparin (242-378.8 nM min, 21.33-23.78 nM, 2.87-3.85 nM/min, 0.747-0.784 nM/min). This trend was also observed in the absence of thrombomodulin.ConclusionsThese results suggest that patients with APS treated with rivaroxaban may be at greater risk for thrombosis compared to warfarin or enoxaparin. The findings may provide insight into the recent studies in patients with triple positive APS randomized to different anticoagulants demonstrating high rates of thrombosis with rivaroxaban. Further studies are necessary to elucidate the clinical significance.     

利伐沙班与决奈达隆联用致消化道出血CSCD

A 78‑year‑old female patient with atrial fibrillation developed tarry stools after regularly taking dronedarone, metoprolol, and rivaroxaban for 3 months. The patient stopped using rivaroxaban by herself for 7 days, and her black stools was gradually improved. After taking rivaroxaban again for 1 month, black stools appeared again, accompanied by fatigue, dizziness, and amaurosis fugax. Her blood pressure was 90/50 mmHg, heart rate was 80 beats/min, and hemoglobin was 55 g/L. Rivaroxaban was discontinued again and supportive treatments such as soft food, acid suppression, fluid replacement, and blood transfusion were given. After 3 days of treatments, the symptoms of fatigue were improved significantly, and no amaurosis recurred when sitting up. Hemoglobin was 75 g/L. After 6 days of treatments, the patient discharged formed yellow soft stools. After excluding gastrointestinal tumors through gastroscopy and tumor marker examination, it was considered that the interaction of dronedarone and rivaroxaban caused the increase of rivaroxaban plasma concentration, which resulted in gastrointestinal bleeding in the patient. The patient′s anticoagulant medication was changed to dabigatran etexilate, and no gastrointestinal bleeding occurred. © 2023 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.     

利伐沙班与低分子量肝素在初次全髋关节置换术后深静脉血栓形成防治中的比较研究

目的 通过比较利伐沙班与低分子量肝素(LMWH)在初次全髋关节置换(THA)术后下肢深静脉血栓形成(DVT)防治中的作用,评估利伐沙班的有效性、安全性以及其足疗程应用防治血栓的必要性. 方法 对2008年1月至2010年4月收治的136例单侧初次行THA患者进行回顾性分析,根据术后预防DVT使用药物不同分为利伐沙班组和LMWH组,每组各68例.利伐沙班组男28例,女40例;平均(61.6±10.7)岁,体质量平均(63.9±11.2) kg.LMWH组男31例,女37例;平均(60.3±12.4)岁,体质量平均(65.5±9.8) kg.两组患者治疗前一般资料差异无统计学意义,具有可比性.LMWH组术后应用时间为1周,利伐沙班组术后应用时间分别为2周38例,5周30例.比较分析两组患者应用药物前、后血红蛋白、血小板、凝血功能情况,以及症状DVT发生率、轻微和严重出血事件发生率. 结果 两组患者手术前、后血红蛋白、血小板、凝血功能、轻微和严重出血事件发生率比较差异均无统计学意义(P＞ 0.05),LMWH组症状DVT发生率为7.4％,利伐沙班组为0,两组比较差异有统计学意义(P＜0.05). 结论 与LMWH比较,初次THA术后DVT防治中利伐沙班更安全、有效,足疗程抗凝十分必要.     

高龄骨折患者围手术期缺血性脑卒中的临床调查分析

目的观察利伐沙班在预防高龄骨折患者围手术期缺血性脑卒中的作用和效果。方法选取98例高龄骨折患者,随机分2组各49例,对照组高龄骨折患者围手术期进行常规低分子肝素皮下注射;实验组在对照组的基础上联合利伐沙班治疗。观察手术前后2组患者围手术期缺血性脑卒中的预防效果并进行统计学分析。结果手术前2组的全血黏度高切、全血黏度低切、红细胞比积、红细胞聚集指数、毛细管血浆黏度等血液流变学指标以及血管性血友病因子、纤维蛋白原、D-二聚体、凝血酶抗凝血酶复合物水平等血清学指标基本相同,差异无统计学意义(P0.05)。手术后,实验组患者的血液流变学和血清学水平较对照组均有明显改善,差异有统计学意义(P0.05)。结论利伐沙班在高龄骨折患者围手术期缺血性脑卒临床疗效明确,可有效改善患者的血液流变学和血清学指标,具有一定临床意义。     

血栓通注射液联合利伐沙班治疗髋关节置换术后下肢深静脉血栓的疗效观察

目的探究血栓通注射液联合利伐沙班治疗髋关节置换术后下肢深静脉血栓的临床疗效。方法选取2011年11月—2014年11月在延安大学附属医院骨科接受髋关节置换术后发生下肢深静脉血栓的患者78例,按照治疗方案不同分为对照组和治疗组,每组各39例。对照组口服利伐沙班片,1片/次,1次/d。治疗组在对照组治疗的基础上静脉滴注血栓通注射液,5 m L溶于0.9%生理盐水250 m L中,1次/d。两组均连续治疗14 d。观察两组的临床疗效,比较两组治疗前后D-二聚体、患肢膝上差、膝下差、静脉血流速度、激活部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB)的变化情况。结果治疗后,对照组和治疗组的总有效率分别为84.62%、97.44%,两组比较差异有统计学意义(P0.05)。治疗后,两组D-二聚体、膝上差、膝下差、FIB均显著降低,患侧血流速度、APTT、PT、TT显著升高,同组治疗前后差异具有统计学意义(P0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异具有统计学意义(P0.05)。结论血栓通注射液联合利伐沙班治疗髋关节置换术后下肢深静脉血栓具有较好的临床疗效,可显著改善患者的凝血状态,具有一定的临床推广应用价值。     

Bleeding and clotting in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia(HHT) is arelatively common inherited vascular disorder that was first described in 1864, and is notable for epistaxis, telangiectasia, and arterial venous malformations. While genetic tests are available, the diagnosis remains clinical, and is based on the Curacao criteria. Patients with HHT are at increased risk for both bleeding and clotting events. Because of these competing complications, hematologists are often faced with difficult clinical decisions. While the majority of management decisions revolve around bleeding complications, it is not infrequent for these patients to require anticoagulation for thrombosis. Any anticoagulation recommendations must take into account the bleeding risks associated with HHT. Recent reviews have found that HHT patients can be safely anticoagulated, with the most frequent complication being worsened epistaxis. Large clinical trials have shown that factor Ⅱa and Ⅹa inhibitors have less intracranial bleeding than warfarin, and basic coagulation research has provided a possible mechanism. This article describes the anticoagulation dilemma posed when a 62-year-old female patient with a history of bleeding events associated with HHT was diagnosed with a pulmonary embolism. The subsequent discussion focuses on the approach to anticoagulation in the HHT patient, and addresses the role of the new oral anticoagulants.     

利伐沙班片的制备及处方优化

目的：制备利伐沙班片剂,优选适合中试生产的最佳处方。方法通过设计不同处方,对增溶剂、崩解剂、黏合剂、填充剂的用量及工艺进行考察,并进行了中试三批放大,测定在四种溶出介质中的溶出曲线、含量均匀度和有关物质等指标。结果用利伐沙班为主药,以乳糖、微晶纤维素为填充剂,以十二烷基硫酸钠为增溶剂,以交联羧甲基纤维素钠为崩解剂,以羟丙基甲基纤维素为黏合剂、以硬脂酸镁为润滑剂,以胃溶型薄膜包衣预混剂为包衣材料,制得利伐沙班片。结论该制剂工艺稳定,制得利伐沙班片（10 mg）与原研市售品溶出行为相似,质量符合规定。