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.     

Potential Role of Direct Oral Anticoagulants in the Management of Heparin-induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a rare, potentially life-threatening condition secondary to unfractionated heparin or low molecular weight heparin exposure. This immune-mediated drug reaction manifests as thrombocytopenia with a paradoxical hypercoagulable state that can result in life-threatening thrombosis. It is imperative to ensure cessation of heparin-based products as soon as HIT is identified. Traditional treatment options include argatroban, bivalirudin, fondaparinux, and danaparoid with a transition to warfarin upon platelet recovery. These anticoagulants are notwithstanding limitations including parenteral administration and routine laboratory monitoring leading to prolonged hospitalizations, emphasizing the need for new therapies. Direct oral anticoagulants (DOACs) have been increasingly investigated for the management of HIT and may overcome the aforementioned challenges of current therapies. The objective of this narrative review is to summarize the current HIT guidelines, discuss limitations to contemporary treatment options, provide insight into the emerging evidence for the DOACs rivaroxaban, apixaban, and dabigatran, and conclude with a clinical summary for their use in this setting. The PubMed, Google Scholar, and MEDLINE databases were searched for peer-reviewed literature from January 1, 2012, to June 31, 2018. Twenty-seven articles met inclusion criteria for review: 1 prospective trial, 5 retrospective cohort studies, and 21 case reports totaling 104 patients treated with a DOAC for HIT. The DOACs prevented new and recurrent thrombosis in 98% (n=102) of cases, and bleeding complications occurred in 3% (n=3). While current literature remains limited, it is suggestive of a potential role of DOACs for HIT, which has led to their integration into the 2018 American Society Hematology Guidelines with a conditional recommendation.     

胃肠镜检查和治疗前应用抗凝剂和/或抗血小板药物的策略研究

该文对国外有关应用抗凝剂和／或抗血小板药物的患者做胃肠镜检壶和治疗前是否需停药的文献进行复习，可为临床医师正确指导胃肠镜检壶和治疗患者正确使用抗凝剂和／或抗血小板药物提供帮助。     

Paper-based dosing algorithms for maintenance of warfarin anticoagulation

We examined the quality of anticoagulation produced by two paper-based warfarin dosing algorithms in a randomized clinical trial of warfarin therapy. Fifty-eight patients were randomized to receive warfarin at a target international normalized ratio (INR) range of 2.1–3.0 and were followed for an average of 2.7 years. As a proportion of total patient-time, the percentage of time spent above, within, and below the therapeutic range was 11%, 71%, and 19% respectively. Fifty-six patients were randomized to receive warfarin at a higher target INR range (3.1–4.0) and had INRs within the therapeutic range for 40% of total patient time. We conclude that the performance, minimal cost, and ease-of-use of these algorithms make them well-suited for patient management within primary-care and research settings. Dr Crowther is a Career Investigator of Heart and Stroke Foundation of Canada This study was supported by the Canadian Institutes for Health Research.     

Association of anticoagulant-related bleeding events with cancer detection in atrial fibrillation: A systematic review and meta-analysis

BackgroundA bleeding episode may herald cancer in the general population. Oral anticoagulants (OACs), the mainstay treatment for atrial fibrillation (AF), are known to increase the risk of bleeding, and may thus promote an earlier diagnosis of cancer. Data regarding the association of bleeding episodes with cancer in patients with AF on OACs are scarce.MethodsIn this systematic review and meta-analysis, we searched electronic databases (Medline, Scopus, and Central) and gray literature sources for studies of patients with nonvalvular AF under any OAC, from inception until 14 October 2020. The primary outcome was the association of bleeding occurrences with the detection of cancer. A subgroup analysis was performed according to OAC type [NOAC (non-vitamin K oral anticoagulant) versus VKA (vitamin K antagonist)].ResultsOverall, 4 studies were included, accounting for a total of 144,362 patients with AF receiving OAC. During follow-up, 816 (0.57%) cases of cancer were confirmed. The presence of a bleeding event, either major or minor, was associated with a higher risk for cancer detection (odds ratio [OR] 8.79, 95% confidence interval [CI] 4.98-15.51, and I² 85%). Heterogeneity was explained after studies were stratified by the type of OAC (NOACs: OR 6.12, 95% CI 4.47-8.37, I² 0%, VKAs: OR 15.16, 95% CI 12.61-18.23, and I² 0%).ConclusionThe detection of a bleeding event could be an alerting sign of cancer in patients with AF on OACs, particularly in patients receiving VKAs.Registration number (DOI)available in https://doi.org/10.17605/OSF.IO/3948R, DOI: 10.17605/OSF.IO/3948R.     

Perioperative atrial fibrillation: A systematic review of evolving therapeutic options in pharmacologic and procedural management

Given the high incidence of atrial fibrillation (AF) in the surgical population and the associated morbidity, physicians managing these complicated patients in the perioperative period need to be aware of the new and emerging trends in its therapy. The cornerstones of AF management have always been rate/rhythm control as well as anticoagulation. Restoration of sinus rhythm remains the fundamental philosophy as it maintains the atrial contribution to cardiac output and improves ventricular function. The recent years have seen a dramatic increase in the number of randomized AF trials that have made significant advances to our understanding of both pharmacologic and procedural management, from the introduction of the new generation of oral anticoagulants (NOAC''s) to catheter approaches for AF ablation. This paper will summarize the newest data that will affect the perioperative management of these patients.