Correction effect of ATP on platelet aggregation and blood coagulation <Emphasis Type="Italic">In Vitro</Emphasis> and in the presence of circulating thrombin in rats

ATP added to plasma samples in concentrations of 5×10⁻³−5×10⁻⁵ M in vitro decreased ADP-induced platelet aggregation. Platelet aggregation stimulated with thrombin under similar experimental in vitro conditions significantly decreased in the presence of 5×10⁻⁶ M ATP and tended to decrease under the influence of ATP in concentrations of 5×10⁻³ and 5×10⁻⁷−5×10⁻⁹ M ATP. When endogenous thrombin in the circulation was stimulated by intravenous infusion of tissue thromboplastin, pretreatment with ATP (4 intramuscular injections, 0.75 mg/kg) produced a correction effect and normalized disturbed anticoagulant activity and platelet aggregation. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 4, pp. 364–366, April, 2007     

Extended thromboprophylaxis in the acutely ill medical patient after hospitalization – a paradigm shift in post-discharge thromboprophylaxis

Venous thromboembolism (VTE) is a significant healthcare burden with approximately 900,000 events annually in the United States, over half of which are healthcare-associated. This number is anticipated to double by 2050. Group prophylaxis strategies confined to the inpatient setting appear to have minimal impact on the reduction of post-discharge VTE in medically ill patients due to shortened lengths of stay and a heterogenous population that includes patients at low risk for VTE. In accordance with current guideline recommendations, very few (<5%) medically ill patients are discharged with extended prophylaxis, which potentially creates a clinical gap for at-risk patients as VTE risk has been shown to persist for up to 90 days. Initial studies of extended thromboprophylaxis in acutely ill medical patients with enoxaparin, rivaroxaban and apixaban showed little to no benefit towards VTE reduction that was consistently outweighed by increased bleeding. The more recent APEX study that compared betrixaban to enoxaparin in an enriched patient population at high-risk for VTE was the first study of extended thromboprophylaxis that showed similar efficacy in VTE prevention without an increase in major bleeding. Based on the APEX results, betrixaban recently gained FDA approval for extended thromboprophylaxis in acutely ill medical patients. Recognition that up to half of medically ill patients are not at sufficient risk to warrant thromboprophylaxis has driven extensive research towards development of scientifically derived and validated VTE risk assessment models intended to identify patients who do not warrant prophylaxis, as well as those at high risk who may derive benefit from extended thromboprophylaxis. This article will review prior and ongoing extended thromboprophylaxis studies, VTE and bleed risk assessment models, incorporation of biomarkers in VTE risk assessment and key issues in the paradigm shift towards individualized VTE prophylaxis in acutely ill medical patients.     

Gender differences on benefits and risks associated with oral antithrombotic medications for coronary artery disease

Introduction: Despite the significant advances in the pharmacological and interventional management of patients with cardiovascular disease (CVD) over the last decades, cardiovascular mortality remains the leading cause of death. Large randomized clinical trials have investigated the efficacy and safety of different antithrombotic medications in patients with CVD. Although female gender is generally underrepresented in these clinical trials, most analyses clearly indicate that both men and women may accrue therapeutic benefits from antithrombotic management strategies.

Areas covered: This review aims to provide a comprehensive and focused update on gender-related comparative clinical studies of antithrombotic therapies in patients suffering from CVD.

Expert opinion: Current evidence supports the understanding of a similar therapeutic effect between genders with signals of an increased risk of bleeding in women. However, important gaps in evidence exist due to the overall limited percentage of women that have been enrolled in randomized controlled trials. A greater awareness of gender-related issues in antithrombotic therapy should be promoted among physicians and further evidence from large clinical trials looking at the safety and efficacy balance of different antithrombotic strategies in women is warranted.     

脉血康胶囊联合巴曲酶治疗突发性耳聋的临床研究

目的探讨脉血康胶囊联合巴曲酶治疗突发性耳聋的临床效果。方法选取天津市泰达医院2015年10月—2017年10月收治的突发性耳聋患者114例,随机分为对照组(57例)和治疗组(57例)。对照组静脉滴注巴曲酶注射液,首剂量为10 BU加入100 mL生理盐水,隔日1次,维持剂量为5 BU/次,每次给药时间1 h。治疗组在对照组基础上口服脉血康胶囊,3粒/次,3次/d。两组均连续治疗10 d。观察两组患者临床疗效,同时比较治疗前后两组患者听力阈值、凝血–抗凝–纤溶系统指标、血液流变学指标和炎性因子水平。结果治疗后,对照组和治疗组的临床总有效率分别为77.2%和91.2%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者0.5、1、2、4 k Hz的听力阈值较治疗前均显著下降(P0.01),且治疗后治疗组听力阈值明显低于对照组(P0.01)。治疗后,两组血浆纤维蛋白原(FIB)水平和血清D-二聚体(D-D)水平均显著下降(P0.01),血清抗凝血酶Ⅲ(ATⅢ)水平显著上升(P0.01),且治疗后治疗组凝血–抗凝–纤溶系统指标优于对照组(P0.01)。治疗后,两组患者红细胞沉降率(ESR)、血浆黏度(PV)值较治疗前明显降低(P0.05),红细胞变形指数(EDI)值明显增加(P0.05),且治疗后治疗组血液流变学指标明显优于对照组(P0.05)。治疗后,两组患者白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α和超敏C反应蛋白(hs-CRP)水平均显著下降(P0.01),且治疗组上述炎性因子水平明显低于对照组(P0.01)。结论脉血康胶囊联合巴曲酶注射液治疗突发性耳聋可短期内消除患者耳周感觉异常、头晕等症状,有效调节凝血–抗凝–纤溶系统平衡,改善血液流变学状态,减轻炎性反应。     

Dabigatran,rivaroxaban, and apixaban are superior to warfarin in Asian patients with non-valvular atrial fibrillation: An updated meta-analysis

BACKGROUNDMost of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation (AF) originated from western countries. AIMTo systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran, rivaroxaban, and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODSMedline, Cochrane, and ClinicalTrial.gov databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. The primary outcome was ischemic stroke. The secondary outcomes were all-cause mortality, major bleeding, intracranial hemorrhage, and gastrointestinal bleeding.RESULTSTwelve studies from East Asia or Southeast Asia and 441450 patients were included. Dabigatran, rivaroxaban, and apixaban were associated with a significant reduction in the incidence of ischemic stroke [hazard ratio (HR) = 0.78, 95% confidence interval (CI): 0.65-0.94; HR = 0.79, 95%CI: 0.74-0.85, HR = 0.70, 95%CI: 0.62-0.78; respectively], all-cause mortality (HR = 0.68, 95%CI: 0.56-0.83; HR = 0.66, 95%CI: 0.52-0.84; HR = 0.66, 95%CI: 0.49-0.90; respectively), and major bleeding (HR = 0.61, 95%CI: 0.54-0.69; HR = 0.70, 95%CI: 0.54-0.90; HR = 0.58, 95%CI: 0.43-0.78; respectively) compared to warfarin.CONCLUSIONDabigatran, rivaroxaban, and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.     

Developing a Conversation Aid to Support Shared Decision Making: Reflections on Designing Anticoagulation Choice

Patient-centered care requires that treatments respond to the problematic situation of each patient in a manner that makes intellectual, emotional, and practical sense, an achievement that requires shared decision making (SDM). To implement SDM in practice, tools—sometimes called conversation aids or decision aids—are prepared by collating, curating, and presenting high-quality, comprehensive, and up-to-date evidence. Yet, the literature offers limited guidance for how to make evidence support SDM. Herein, we describe our approach and the challenges encountered during the development of Anticoagulation Choice, a conversation aid to help patients with atrial fibrillation and their clinicians jointly consider the risk of thromboembolic stroke and decide whether and how to respond to this risk with anticoagulation.     

Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Liver Disease

BackgroundAdvanced liver disease is known to increase the risk for bleeding and affects the hepatic clearance and metabolism of drugs. Subjects with active liver disease were excluded from pivotal clinical trials of direct oral anticoagulants (DOACs), so the evidence regarding the efficacy and safety of DOACs in patients with liver disease is lacking.ObjectivesThe aim of this study was to compare DOACs with warfarin in patients with nonvalvular atrial fibrillation and liver disease.MethodsUsing the Korean National Health Insurance Service database, subjects with atrial fibrillation and active liver disease treated with oral anticoagulation were included (12,778 with warfarin and 24,575 with DOACs), and analyzed ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome. Propensity score weighting was used to balance covariates between the 2 groups.ResultsDOACs were associated with lower risks for ischemic stroke (hazard ratio [HR]: 0.548; 95% confidence interval [CI]: 0.485 to 0.618), intracranial hemorrhage (HR: 0.479; 95% CI 0.394 to 0.581), gastrointestinal bleeding (HR: 0.819; 95% CI: 0.619 to 0.949), major bleeding (HR: 0.650; 95% CI: 0.575 to 0.736), all-cause death (HR: 0.698; 95% CI: 0.636 to 0.765), and the composite outcome (HR: 0.610; 95% CI: 0.567 to 0.656) than warfarin. Among the total study population, 13% of patients (n = 4,942) were identified as having significant active liver disease. A consistent benefit was observed in patients with significant active liver disease (HR for the composite outcome: 0.691; 95% CI: 0.577 to 0.827).ConclusionsIn this large Asian population with atrial fibrillation and liver disease, DOACs showed better effectiveness and safety than warfarin, which was consistent in those with significant active liver disease.