Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibition

BACKGROUND/OBJECTIVE: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. METHODS: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion, n=6); ZK-807834-Dose 2 (20 microg kg(-1) bolus + 0.75 microg kg(-1) min(-1) infusion; n=6); enoxaparin (1 mg kg(-1) bolus; n=6); or saline (n=6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. RESULTS: The prothrombin time ratio was 2.2 +/- 0.1; 1.4 +/- 0.3; 1.2 +/- 0.9 and 1.1 +/- 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 +/- 226 x 10(6) cm(-2); P = 0.008), whereas ZK-807834-Dose 2 (2325 +/- 768) and enoxaparin (1236 +/- 383) were not different from saline (2776 +/- 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 +/- 185). Neither ZK-807834-Dose 2 (1588 +/- 480) nor enoxaparin (1618 +/- 686) was different from saline control (2222 +/- 598). CONCLUSIONS: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective.     

围术期维持活体部分移植小肠血供的措施

目的：探讨围术期维持移植小肠血液灌注的方法，方法：男，18岁，短肠综合征患者，全麻下接受其父亲供给末段回肠150cm，行活体部分小肠移植，围主期维持出入量平衡，中度等容血液稀释，选用扩血管药，防止血管痉挛，以及抗凝治疗，结果：术的31d脱离肠外营养，至今已术后34mo，未发生移植小肠明显缺血性改变。结论：采用上述方法匀是维持围术期移植小肠血供的重要措施。     

Anticoagulant Activity of Fucoidan from Brown Algae Fucus evanescens of the Okhotsk Sea

In vitro and in vivo experiments showed that anticoagulant activity of sulfated polysaccharide from Fucus evanescens (brown algae of the Okhotsk Sea) was similar to that of heparin. Anticoagulant properties of fucoidan are determined by thrombin inhibition mediated via plasma antithrombin III.     

直接凝血酶抑制剂比伐卢定的研究现状

比伐卢定在2000年经美国食品药品管理局批准上市,是直接的、特异的、可逆的凝血酶抑制剂,具有抗凝效果的可预测性、不诱导血小板减少及对纤维蛋白结合的凝血酶有效等优势,克服了肝素、水蛭素的局限性。本文对其药理学特点、药效学与药代动力学、药物相互作用、临床应用与不良反应等进行简要综述。     

Review of enoxaparin and its clinical applications in venous and arterial thromboembolism

Venous and arterial thromboembolic disorders are common medical conditions that are associated with considerable morbidity and mortality. Unfractionated heparin (UFH) and its derivatives, the low molecular weight heparins (LMWHs), are the anticoagulants of choice when a rapid anticoagulant effect is required. LMWHs have several advantages over UFH, including a longer plasma halflife and higher bioavailability; a predictable dose response, which enables once- or twice-daily dosing; and a more convenient route of administration (subcutaneous instead of intravenous), which enables patients to self-inject in an out-patient setting. Enoxaparin is a LMWH prepared by alkaline hydrolysis of the benzylin ester of UFH. The efficacy of enoxaparin in the management of venous and arterial thromboembolism has been shown in a wide range of patient groups using doses ranging from fixed doses of 20 – 60 mg o.d. and 0.75 – 1.5 mg/kg b.i.d. Other doses, such as 80 mg/day for pregnant women with combined thrombophilic defects, have also been studied. The use of subcutaneous enoxaparin as an effective and safe home treatment for patients with acute proximal deep vein thrombosis (DVT) has been demonstrated. The benefits of preventing venous thromboembolic events with enoxaparin include reducing the costs associated with investigating the symptoms of DVT, acute treatment and hospitalisation, and potentially preventing the development of post-thrombotic syndrome, while improving quality of life and so making the treatment cost effective. In contrast to other LMWHs, enoxaparin has been shown to provide better outcomes than UFH in the treatment of unstable angina and non-ST-segment elevation myocardial infarction, without increasing major bleeding. Adverse events with enoxaparin are infrequent; the most common events are minor bleeding complications. It should be noted that different doses or indications are approved in each country.     

Biting Innovations of Mosquito-Based Biomaterials and Medical Devices

Mosquitoes are commonly viewed as pests and deadly predators by humans. Despite this perception, investigations of their survival-based behaviors, select anatomical features, and biological composition have led to the creation of several beneficial technologies for medical applications. In this review, we briefly explore these mosquito-based innovations by discussing how unique characteristics and behaviors of mosquitoes drive the development of select biomaterials and medical devices. Mosquito-inspired microneedles have been fabricated from a variety of materials, including biocompatible metals and polymers, to mimic of the mouthparts that some mosquitoes use to bite a host with minimal injury during blood collection. The salivary components that these mosquitoes use to reduce the clotting of blood extracted during the biting process provide a rich source of anticoagulants that could potentially be integrated into blood-contacting biomaterials or administered in therapeutics to reduce the risk of thrombosis. Mosquito movement, vision, and olfaction are other behaviors that also have the potential for inspiring the development of medically relevant technologies. For instance, viscoelastic proteins that facilitate mosquito movement are being investigated for use in tissue engineering and drug delivery applications. Even the non-wetting nanostructure of a mosquito eye has inspired the creation of a robust superhydrophobic surface coating that shows promise for biomaterial and drug delivery applications. Additionally, biosensors incorporating mosquito olfactory receptors have been built to detect disease-specific volatile organic compounds. Advanced technologies derived from mosquitoes, and insects in general, form a research area that is ripe for exploration and can uncover potential in further dissecting mosquito features for the continued development of novel medical innovations.     

长期使用华法林抗凝的非瓣膜性房颤患者围手术/操作期使用NOAC桥接的抗凝方案研究

目的：探讨使用非维生素K拮抗剂的口服抗凝药物（NOAC）代替肝素类药物在围手术/操作期患者进行桥接抗凝的可行性。方法：本研究为前瞻性观察研究,2018年8月至2021年5月入选长期使用华法林抗凝的非瓣膜性房颤患者,观察患者在围手术/操作期使用NOAC桥接抗凝后,围手术/操作期以及术后30天内栓塞事件与出血事件的发生率。结果：共入选患者21例,其中4例行肠镜检查,3例行胃镜检查,8例行拔牙操作,3例行眼科相关操作,3例行皮肤科相关操作。患者的平均年龄（70.8±8.5）岁,女性有9例,平均CHA2DS2-VASc评分（3.0±1.0）分,平均HAS-BLED评分（1.4±0.7）分。21例术后30天均未出现出血事件与栓塞事件。结论：对于非瓣膜性房颤患者,采取NOAC在围手术/操作期进行桥接抗凝,具有一定的可行性。