Drug-induced thrombocytopenia after anticoagulation with rivaroxaban

A 66-year-old man presented to the emergency department with complaints of dark-colored stool and rash developing over the last couple of days. The patient was started on rivaroxaban and flecainide for months prior for atrial fibrillation. Upon arrival, he was awake, alert, and oriented with a blood pressure of 111/63 mm Hg, heart rate of 68 beats per minute, and oxygen saturation of 96% on room air. A review of systems was unremarkable with the exception of skin rash and light-headedness. The patient's initial laboratory results were significant for red blood cell (RBC) count of 4.05 × 10⁶/mcL, hemoglobin of 12.1 g/dL, hematocrit of 35.6%, and platelet count of 1 × 103/mcL. Aggressive hydration was started in the ED, initially with two 1-L boluses of normal saline followed by an infusion of 10 mL/h. One unit of platelets was transfused. Rivaroxaban and flecainide were held on admission. Twenty-four hours after admission, the patient was initiated on immune globulin (IVIG) Gammagard (Baxter, West Lake, CA), 75 g on 3 consecutive days and steroids for possible immune thrombocytopenia. His platelet count steadily improved over the 6-day period to 119 × 103/mcL on the day of hospital discharge. This is the second reported case of possible rivaroxaban-induced thrombocytopenia.     

A critical analysis of the COMPASS trial with respect to benefit-risk assessment using the numbers needed to treat: Applicability and relevance in Indian patients with stable cardiovascular disease

The recently published Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial evaluated the hypothesis that rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary prevention. In India, stable cardiovascular disease occurs in a much younger age group relative to the rest of the world.Our critical analysis of COMPASS trial showed that the younger age group appeared to derive greater benefit from the rivaroxaban + aspirin combination (relative to aspirin alone) as seen with number needed to treat metrics as compared to the older age group.     

利伐沙班在冠心病合并心房颤动患者经皮冠状动脉介入术后抗栓治疗中的作用

目的探讨利伐沙班在冠心病合并心房颤动患者PCI术后抗栓治疗中的疗效及安全性。方法选取我院2016年08月~2018年08月收治的冠心病合并房颤并行经皮冠状动脉介入(PCI)术患者104例,随机分为试验组和对照组,每组各52例。术后两组均给予三联抗栓药物治疗6个月,之后双联抗栓药物治疗至12个月,其中试验组给予利伐沙班治疗,对照组给予华法林治疗。比较两组患者PCI前后凝血功能,同时观察血栓栓塞事件和出血事件发生情况。结果治疗后与治疗前比较,两组活化部分凝血活酶时间(aPTT)、凝血酶原时间(PT)均明显升高,差异有统计学意义(P<0.05),与试验组比较,对照组aPTT、PT升高更显著(P<0.05)。两组血栓栓塞事件发生率比较差异无统计学意义(P>0.05);两组出血事件发生率比较,试验组较对照组明显降低,差异有统计学意义(P<0.05)。结论利伐沙班在冠心病合并心房颤动患者PCI术后抗栓治疗中的疗效与华法林相当,而出血发生率低,安全性较高。     

Italian intersociety consensus statement on antithrombotic prophylaxis in hip and knee replacement and in femoral neck fracture surgery

Anticoagulant prophylaxis for preventing venous thromboembolism (VTE) is a worldwide established procedure in hip and knee replacement surgery, as well as in the treatment of femoral neck fractures (FNF). Different guidelines are available in the literature, with quite different recommendations. None of them is a multidisciplinary effort as the one presented. The Italian Society for Studies on Haemostasis and Thrombosis (SISET), the Italian Society of Orthopaedics and Traumatology (SIOT), the association of Orthopaedists and Traumatologists of Italian Hospitals (OTODI), together with the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI) have set down easy and quick suggestions for VTE prophylaxis in hip and knee surgery as well as in FNF treatment. This inter-society consensus statement aims at simplifying the grading system reported in the literature, and its goal is to benefit its clinical application. Special focus is given to fragile patients, those with high bleeding risk, and those receiving chronic antiplatelet (APT) and vitamin K antagonists treatment. A special chapter is dedicated to regional anaesthesia and VTE prophylaxis.     

HPLC-MS/MS测定肝功能不全患者血浆利伐沙班的浓度及其临床应用

摘 要 目的：建立高效液相色谱 串联质谱(HPLC-MS/MS)法测定肝功能不全患者血浆中利伐沙班浓度的方法。 方法: 采用Agilent SB C18色谱柱（50 mm×2.1 mm,1.8 μm）;流动相：乙腈 10 mmol·L-1醋酸铵缓冲液 冰醋酸（50∶50∶0.45）;流速：0.2 ml·min-1,柱温：20℃。质谱条件为电喷雾离子源,正离子模式检测,扫描方式为多反应离子监测（MRM）模式;内标法定量,用于定量分析的离子反应为m/z 436.1→145.1（利伐沙班）,m/z 837.0/679.4（内标罗红霉素）。 结果: 血浆利伐沙班浓度在5~1 000 ng·ml-1范围内线性关系良好（r=0.999 2）。日内和日间精密度均<7%,绝对回收率98.19%~103.47%,基质效应85.53%~104.06%。血浆样品室温放置6 h、反复冻融3次及-20℃冷冻30 d稳定性良好,样品浓度均无显著变化。应用本文所建立的方法测定了3例肝功能不全患者服用利伐沙班后的血药浓度,发现餐后服用和空腹服用利伐沙班可能会影响其吸收,而肝功能不全的严重程度可能会使利伐沙班的体内药动学存在较大差异。 结论: 所建方法快速简便、灵敏准确,可用于测定人血浆中利伐沙班的浓度,并可为利伐沙班在人体中的药动学研究提供方法学基础。     

不同时间点利伐沙班预防髋关节置换术后深静脉血栓形成的疗效研究

目的 比较在围手术期不同时间点使用利伐沙班预防髋关节置换术后下肢深静脉血栓（DVT）形成的效果和安全性。方法 选取2014 年1 月-2016 年10 月在该院行髋关节置换手术患者150 例。根据患者入选标准随机分成4 组,A 组术前72 h 使用利伐沙班,B 组术前48 h 使用利伐沙班,C 组术前24 h 使用利伐沙班,D 组术后6 h 使用利伐沙班。观察4 组患者在围手术期的深静脉血栓发生率、出血并发症与记录围手术期出血量。结果 A 组发生DVT 1 例（2.5%）,B 组发生DVT 4 例（11.1%）,C 组发生DVT 5 例（13.2%）,D 组发生DVT 11 例（30.6%）。A 组DVT 发生率与B、C、D 组比较,差异有统计学意义（P <0.05）,A 组低于B、C、D 组。围手术期出血量上4 组间比较差异无统计学意义（P >0.05）。结论 术前72 h 使用利伐沙班预防髋关节置换术后发生DVT 的效果好,安全性高。     

Practical Considerations in the Use of Novel Oral Anticoagulants for Stroke Prevention in Nonvalvular Atrial Fibrillation

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia associated with an increased risk of stroke. The role of anticoagulation therapy in the prevention of thrombosis and stroke is of critical importance for patients with AF. Limitations with vitamin K antagonists (VKAs), the current standard of care, have led to the development of novel oral anticoagulants (NOACs) that target either thrombin (dabigatran etexilate) or activated factor X (rivaroxaban, apixaban, and edoxaban). In comparison with traditional VKAs such as warfarin, these NOACs offer several pharmacologic advantages, including rapid onset of action, no significant food interactions, low potential for drug–drug interactions, and no requirement for routine coagulation monitoring. Completed phase‐III clinical trials have demonstrated the therapeutic potential of dabigatran, rivaroxaban, and apixaban in comparison with warfarin for stroke prevention in patients with nonvalvular AF (NVAF). While the future utility of NOACs in preventing stroke in patients with NVAF looks promising, several practical issues, including the current lack of a reversal strategy and use of these agents in older patients with renal dysfunction, must be considered. Clinician and patient understanding of such issues will be important for the safe and effective use of NOACs.     

80岁以上非瓣膜性心房颤动患者抗凝方案的调查研究

背景　目前80岁以上非瓣膜性心房颤动患者的抗凝治疗比例普遍偏低,这类人群的抗凝实际情况与指南存在较大差距,抗凝方案的选择缺乏临床证据。目的　调查80岁以上非瓣膜性心房颤动住院患者抗凝方案的选择及预后情况。方法　从HIS系统筛选2016年9月-2018年9月浙江中医药大学附属第二医院首次诊断非瓣膜性心房颤动或既往诊断但未进行抗凝治疗的80岁以上患者516例为研究对象,根据出院时抗凝治疗方案不同将患者分为华法林组、利伐沙班组、达比加群酯组、不抗凝组。收集患者性别、年龄、吸烟史、合并疾病〔高血压、糖尿病、冠状动脉疾病、心肌病、心力衰竭、慢性阻塞性肺疾病（COPD）〕、心房颤动类型（持续性心房颤动、阵发性心房颤动、永久性心房颤动）、缺血性脑卒中史、出血史、估算肾小球滤过率（eGFR）、卒中风险评分（CHA2DS2-VASc评分）、出血风险评分（HAS-BLED评分）、抗凝治疗时间、抗血小板药物应用情况、不良反应（出血事件、缺血性脑卒中、出血性脑卒中、死亡）等情况。采用二元Logistic回归分析探讨患者出现死亡、缺血性脑卒中、出血事件的影响因素。结果　516例患者中接受抗凝治疗137例（26.6%）,其中口服华法林21例（4.1%）、口服利伐沙班67例（13.0%）、口服达比加群酯49例（9.5%）;不抗凝治疗患者379例（73.5%）,其中应用单药抗血小板266例（51.6%）、应用双联抗血小板药物53例（10.3%）、未应用抗血小板药物60例（11.6%）。4组患者性别、年龄、吸烟史、合并疾病（高血压、糖尿病、冠状动脉疾病、心肌病、心力衰竭、COPD）、缺血性脑卒中史、出血史、eGFR、CHA2DS2-VASc评分、HAS-BLED评分、出血（轻度、中度、严重）、出血性脑卒中发生率比较,差异均无统计学意义（P>0.05）。4组患者缺血性脑卒中发生率及死亡率比较,差异均有统计学意义（P<0.05）。华法林组、利伐沙班组、达比加群酯组抗凝治疗时间比较,差异无统计学意义（P>0.05）。二元Logistic回归分析结果显示,CHA2DS2-VASc评分、抗凝治疗方案是缺血性脑卒中的影响因素（P<0.05）,抗凝治疗方案是患者发生死亡事件的影响因素（P<0.05）,HAS-BLED评分是患者发生出血事件的影响因素（P<0.05）。结论　80岁以上非瓣膜性心房颤动患者抗凝治疗比例较低。不抗凝治疗（包括口服抗血小板药物）增加了患者死亡、缺血性卒中风险,而华法林与新型口服抗凝药相比同样安全有效,未增加出血及死亡风险。