Use of Direct Oral Anticoagulants in Morbidly Obese Patients

In 2016, the International Society on Thrombosis and Haemostasis (ISTH) published guidelines advising caution when using direct oral anticoagulants (DOACs) in patients with morbid obesity due to limited clinical efficacy and safety data supporting their use in this patient population. In this review, we analyzed published articles in the MEDLINE database (from inception through May 29, 2019), and the Cochrane Library, Google Scholar, and EMBASE databases (from inception through April 26, 2019) that evaluated morbidly obese patients with atrial fibrillation (AF) or venous thromboembolism (VTE) who received DOACs. A total of 19 studies, which included pharmacokinetic studies, original phase III trials for the DOACs, post hoc analyses of phase III trials, and retrospective cohort studies, were evaluated. Although currently available data do not indicate that using DOACs in the morbidly obese is problematic, DOAC-specific pharmacokinetic variations have been observed. Additionally, less data evaluating DOAC efficacy and safety exist for VTE treatment compared with the data for stroke prevention in patients with AF. The overall quality of the studies included in this review was low due to limited prospective randomized trial data, limiting the ability to form definitive judgments on efficacy and safety DOACs in the morbidly obese. Continued caution is recommended when considering DOAC use in the morbidly obese, particularly for those requiring anticoagulation for VTE treatment, until additional higher-quality data become available.     

新型直接口服抗凝药物与胃肠道出血的研究进展

2010年,一类新型直接口服抗凝药(DOAC)被批准用于非瓣膜性心房颤动患者预防血栓性脑卒中及治疗静脉血栓栓塞症(VTE)/肺栓塞(PE).与传统口服抗凝药维生素K拮抗剂(VKA)相比,DOAC的抗凝效果确切,安全性更好、服用更方便,且更少引起颅内出血事件,但可能会增加胃肠道的出血风险.由于DOAC的半衰期短,大多数胃肠道出血无需特殊处理,但在出血危及生命或急诊手术时需给予逆转剂抵抗DOAC的抗凝作用.本文旨在对DOAC相关胃肠道出血的发生率、预防治疗及DOAC特异性逆转剂等作一综述.     

共无定形体系改善低水溶性药物达比加群酯甲磺酸盐和他达拉非的溶出行为及稳定性

达比加群酯甲磺酸盐(DE)和他达拉非(TD)为低水溶性BCS Ⅱ类药物,本研究通过减压旋蒸法制备DE-TD共无定形,以提高两者溶出度,改善生物利用度。利用X射线粉末衍射法、差量扫描量热分析、傅里叶变换红外光谱、热重分析等手段进行表征,并考察共无定形的溶出行为和稳定性。结果表明,制备获得的DE-TD共无定形物的T_g为119 ℃,红外光谱表明在DE的N-H基团与TD的C==O基团之间可能形成氢键。特性溶出和粉末饱和溶出实验表明,共无定形样品相较于晶体药物可显著改善两种药物的溶出度。DE无定形样品在25 ℃/75%RH恒温恒湿条件下放置10 d即发生转晶,而共无定形样品在25 ℃/60%RH和40℃/75%RH条件下90 d均无转晶现象。     

Direct oral anticoagulants for atrial fibrillation in patients with congenital factor VII deficiency

The management of anticoagulant therapy (OAT) in patients with factor VII (FVII) deficiency is a very challenging clinical issue, as warfarin further reduces FVII levels, thus potentially increasing bleeding risk. On the other hand, the International Normalized Ratio test is misleading in such patients, as they do not reflect the actual level of global inhibition of the coagulation system. We report here three cases of patients with a moderate FVII deficiency and receiving direct oral anticoagulants (DOAC) for prevention of cardioembolism in atrial fibrillation. Of note, two of them experienced a treatment failure while on warfarin, while DOAC treatment was not associated with thrombotic or hemorrhagic adverse events. DOAC are very attractive for the management of OAT in FVII deficient patients, because they do not require monitoring by tests affected by the inherited defect, and their mechanism of action is FVII‐independent.     

Persistent ductus arteriosus in a 72-year-old woman with paroxysmal atrial fibrillation and depression syndrome: a therapeutic and diagnostic problem

Treating the elderly is often problematic, especially when congenital heart disease is diagnosed. The aim of this study is to present the case of a 72-year old woman with depression syndrome, paroxysmal atrial fibrillation and past cerebral stroke, in whom persistent ductus arteriosus Botalli was diagnosed. Due to exacerbation of the depressive syndrome, she did not give her consent to further diagnostics, possible interventional procedures and treatment with oral anticoagulants. After intermission of the therapy she was treated with dabigatran. The patient is still undergoing outpatient treatment and so far, no cerebrovascular episodes have been recorded.