连续性血液净化中阿加曲班与枸橼酸钠的抗凝效果及安全性比较

 目的 比较阿加曲班和枸橼酸钠在连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)中的有效性和安全性。方法 选取2018-09至2019-05医院行CRRT治疗的患者132例,随机分为阿加曲班组60例和枸橼酸钠组72例,分别给予阿加曲班和枸橼酸钠抗凝治疗,阿加曲班组监测体内活化凝血时间(activated clotting time,ACT),枸橼酸钠监测ACT及血钙,同时记录两组患者透析前后血常规、血生化指标,尿素下降率、滤器及管路凝血情况,以及治疗后24 h内组织器官出血情况。结果 两组患者透析前ACT均在正常范围内,阿加曲班组ACT 5 min、2 h和4 h均显著升高,差异有统计学意义(P＜0.05),透析1 h后ACT显著下降至正常范围;枸橼酸钠组透析4 h和透析后ACT均无明显变化。枸橼酸钠组透析前、透析中、透析后体内游离钙均无明显变化;透析中体外游离钙均低于同时间体内游离钙水平。两组患者治疗前后血红蛋白及血小板较治疗前均无明显变化,血肌酐水平均显著下降,差异有统计学意义(P＜0.05)。两组患者治疗时间、URR值、管路滤器凝血情况及出血事件对比差异无统计学意义。结论 阿加曲班和枸橼酸钠在CRRT治疗中均为有效和安全的抗凝剂。对有高出血风险的患者选择枸橼酸钠更佳。     

Addendum to British Society for Haematology Guidelines on Investigation and Management of Antiphospholipid syndrome, 2012 (Br. J. Haematol. 2012; 157: 47–58): use of direct acting oral anticoagulants

We studied the efficacy and safety of humanized CAR-T therapy following intensive chemotherapy for refractory/relapsed (R/R) acute lymphoblastic leukaemia (B-ALL). Twenty-three patients with R/R B-ALL were pretreated with intensive chemotherapy (fludarabine combined with medium-dose cytarabine) 12 days before CAR-T therapy. Adverse events (AEs), curative effects, infection indicators and cytokine release syndrome (CRS) were monitored. Each of the 23 patients received a dose of 1·0 × 10⁶ cells/kg CAR-T cell infusion on day 0. After 14 days, 19 patients (82·61%) achieved complete response (CR) or CR with incomplete count recovery. No survival benefit was achieved with consolidative haematopoietic stem-cell transplantation (HSCT), with a median follow-up of 14·0 months (range, 1·5–21·0 months). The notable AEs were grade 1–2 CRS in 18 patients, while the other five patients were grade 3 CRS. No patients died of CRS. Only one patient died of respiratory failure due to cytomegalovirus infection 24 days after infusion. The proportion of leukaemic cells in bone marrow on infusion day and the peaks of IL-6, TNF-α and IL-8 levels were correlated with CRS levels. A lower disease burden was achieved by intensive lymphodepleting chemotherapy, and the subsequent CAR-T therapy had a high response and manageable toxicity. Trial registration: The patients were enrolled in a clinical trial of ChiCTR-ONN-16009862, and ChiCTR1800019622.     

Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism. The incidence of venous thromboembolism among COVID-19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions. D-dimer might help in early recognition of these high-risk patients and also predict outcome. Preliminary data show that in patients with severe COVID-19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis-induced coagulopathy criteria or with markedly elevated d-dimer. Recent recommendations suggest that all hospitalized COVID-19 patients should receive thromboprophylaxis, or full therapeutic-intensity anticoagulation if such an indication is present.     

Defining and managing patients with non-ST-elevation myocardial infarction: Sorting through type 1 vs other types

Advances in cardiovascular (CV) imaging, redefined electrocardiogram criteria, and high-sensitivity CV biomarker assays have enabled more differentiated etiological classification of myocardial infarction (MI). Type 1 MI has a different underlying pathophysiology than type 2 through type 5 MI; type 1 MI is characterized primarily by intracoronary atherothrombosis and the other types by a variety of mechanisms, which can occur with or without an atherosclerotic component. In type 2 MI, there is evidence of myocardial oxygen supply-demand imbalance unrelated to acute coronary atherothrombosis. Types 1 and 2 MI are spontaneous events, while type 4 and type 5 are procedure-related; type 3 MI is identified only after death. Most type 1 and type 2 MI present as non-ST-elevation MI (NSTEMI), although both types can also present as ST-elevation MI. Because of their different underlying etiologies, type 1 and type 2 NSTEMI have different presentation and prognosis and should be managed differently. In this article, we discuss the epidemiology, prognosis, and management of NSTEMI occurring in the setting of underlying type 1 or type 2 pathophysiology. Most NSTEMI (65%–90%) are type 1 MI. Patients with type 2 MI have multiple comorbidities and causes of in-hospital mortality among these patients are not always CV-related. It is important to distinguish between type 1 and type 2 NSTEMI early in the clinical course to allow for the use of the most appropriate treatments that will provide the greatest benefit for these patients.     

Coagulopathy in COVID‐19

The COVID‐19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)‐like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19. The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.     

心血管系统常用药物对新型冠状病毒肺炎感染风险及不良预后的影响

心血管疾病是新型冠状病毒肺炎(新冠肺炎)最为常见的合并症,在新冠肺炎大流行期间降压、降脂、抗血小板、抗凝、降糖及抗心律失常等心血管系统常用药物的安全性和有效性尚未形成统一明确的认识,相关指南也有待进一步完善。随着全球新冠肺炎病例数量的增加和第二波感染的发生,更好地了解这些药物对新冠肺炎患者的影响是当务之急。本文旨在总结心血管系统常用药物对新冠肺炎感染风险以及不良预后的关联,并对合并心血管疾病的新冠肺炎患者用药提出建议。