Cost-effectiveness of prophylactic low molecular weight heparin in pregnant women with a prior history of venous thromboembolism

PURPOSE: Women with a history of prior venous thromboembolism have an increased risk for recurrence during pregnancy. Although thromboprophylaxis reduces this risk, recent evidence suggests that, in many cases, prophylaxis can be safely withheld because the estimated recurrence risk is very low. The balance of risks and benefits in women with different recurrence risks has not been examined. METHODS: We developed a Markov state transition decision analytic model to compare prophylactic low molecular weight heparin to expectant management for pregnant women with a single prior venous thromboembolism. A lifetime time horizon and societal perspective were assumed. Input data were obtained by literature review. Outcomes were expressed as U.S. dollars per quality-adjusted life-year (QALY). RESULTS: For "low-risk" women with a prior venous thromboembolism associated with a transient risk factor and no known thrombophilic condition (recurrence risk 0.5%), expectant management was both more effective and less costly than prophylaxis. For "high-risk" women with prior idiopathic venous thromboembolism or known thrombophilic condition (recurrence risk 5.9%), prophylaxis was associated with a reasonable cost-effectiveness ratio (USD 38,700 per QALY) given a risk of bleeding complications <1.0% (base case 0.5%). CONCLUSION: For low-risk women with prior venous thromboembolism, expectant management during pregnancy leads to better outcomes than administration of prophylactic low molecular weight heparin. For high-risk women, antepartum thromboprophylaxis is a cost-effective use of resources.     

生骨胶囊联合低分子肝素治疗脊柱术后下肢深静脉血栓48例疗效观察

目的 观察生骨胶囊联合低分子肝素对脊柱术后下肢深静脉血栓(DVT)疗效及安全性的影响。方法 选择2015年12月至2016年11月于石家庄市第一医院行脊柱外科手术病人96例作为研究对象,采用随机数字表法将其分为观察组(48例)与对照组(48例)。对照组给予低分子肝素治疗,每天4 100 IU,皮下注射。观察组则在对照组用药治疗基础上加以口服生骨胶囊,5粒/次,3次/天。观察两组临床疗效、DVT发生率、不良反应发生情况以及治疗前后血液流变学、腘静脉内径(POPV)、股浅静脉内径(FSV)等变化情况。结果 观察组总有效95.83%高于对照组77.08%,DVT发生率4.17%低于对照组20.83%,差异有统计学意义(P＜0.05)。治疗后观察组PT、FIB、D-D指标水平较高于治疗前,差异有统计学意义(P＜0.05)。治疗后观察组FIB(4.02±0.46) g/L、D-D(385.24±26.41) μg/L指标水平较低于对照组FIB(4.63±0.51) g/L、D-D(511.61±22.29) μg/L,差异有统计学意义(P＜0.05)。治疗前两组FSV与POPV检测结果对比,差异无统计学意义(P＞0.05);治疗后观察组FSV与POPV较治疗前对比,差异无统计学意义(P＞0.05);治疗后对照组FSV(7.03±1.79) mm与POPV(7.96±1.63) mm显著低于观察组FSV(8.52±1.23) mm与POPV(9.52±1.23)mm,差异有统计学意义(P＜0.05)。治疗期间两组用药不良反应发生率差异无统计学意义(P＞0.05)。结论 生骨胶囊与低分子肝素联合治疗有助于降低脊柱术后下肢深静脉血栓发生率,加速病人术后康复,改善血液流变学,安全性良好,临床普及价值高。     

Heparin microparticle effects on presentation and bioactivity of bone morphogenetic protein-2

Biomaterials capable of providing localized and sustained presentation of bioactive proteins are critical for effective therapeutic growth factor delivery. However, current biomaterial delivery vehicles commonly suffer from limitations that can result in low retention of growth factors at the site of interest or adversely affect growth factor bioactivity. Heparin, a highly sulfated glycosaminoglycan, is an attractive growth factor delivery vehicle due to its ability to reversibly bind positively charged proteins, provide sustained delivery, and maintain protein bioactivity. This study describes the fabrication and characterization of heparin methacrylamide (HMAm) microparticles for recombinant growth factor delivery. HMAm microparticles were shown to efficiently bind several heparin-binding growth factors (e.g. bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2)), including a wide range of BMP-2 concentrations that exceeds the maximum binding capacity of other common growth factor delivery vehicles, such as gelatin. BMP-2 bioactivity was assessed on the basis of alkaline phosphatase (ALP) activity induced in skeletal myoblasts (C2C12). Microparticles loaded with BMP-2 stimulated comparable C2C12 ALP activity to soluble BMP-2 treatment, indicating that BMP-2-loaded microparticles retain bioactivity and potently elicit a functional cell response. In summary, our results suggest that heparin microparticles stably retain large amounts of bioactive BMP-2 for prolonged periods of time, and that presentation of BMP-2 via heparin microparticles can elicit cell responses comparable to soluble BMP-2 treatment. Consequently, heparin microparticles present an effective method of delivering and spatially retaining growth factors that could be used in a variety of systems to enable directed induction of cell fates and tissue regeneration.     

儿童重症监护病房患儿深静脉血栓的临床研究进展

近年来,儿童深静脉血栓发病逐渐增多。若栓子脱落,易引起肺栓塞等并发症,轻者致残,重者致死,严重危害患儿生活质量和生命,因此早期预防和及时治疗有助于提高存活率。由于儿童病情的复杂多变性和特殊性,且缺乏大规模试验和统计,目前国内外尚无统一的儿童预防和治疗标准。文章综合了目前有关的临床进展,介绍了深静脉血栓的特点,为深静脉血栓预防、诊断和治疗提供参考。     

微量泵持续泵注肝素联合疏血通治疗进展性脑梗死的临床研究

目的 观察微量泵持续泵注肝素联合疏血通治疗进展性脑梗死患者的疗效,探讨进展性脑梗死的治疗方案.方法 山东省莱州市人民医院内一科自2004年6月至2009年12月共收治进展性脑梗死患者186例,其中87例(治疗组)应用微量泵泵注肝素联合静滴疏血通治疗,99例(对照组)采用低分子肝素皮下注射治疗,其他治疗相同,于治疗后第3、14天进行神经功能缺损评分观察患者的病情进展情况和疗效.结果治疗后第3天,与对照组比较,治疗组患者立即停止进展发生率较高,而中度以上进展发生率较低,差异有统计学意义(P<0.05),轻度进展发生率2组之间差异无统计学意义(P>0.05);治疗后第14天,与对照组比较,治疗组患者中轻型脑梗死患者所占比例较高,重型较低,差异有统计学意义(P<0.05),中型在2组之间差异无统计学意义(P>0.05).结论 应用微量泵持续静脉泵注肝素联合疏血通治疗进展性脑梗死疗效较好.     

低分子肝素钙治疗慢性肺源性心脏病急性发作期64例疗效观察

目的评价低分子肝素钙治疗慢性肺源性心脏病（肺心病）急性发作期的疗效及安全性。方法选择我院慢性肺心病急性发作患者124例，随机分为两组，两组患者均根据药物敏感试验选择有效性抗生素，扩血管、强心利尿，止咳化痰，低流量持续吸氧，维持水电解质平衡等常规治疗，治疗组患者在此基础上加用低分子肝素钙4100U，2次／d，腹部皮下注射，疗程均为7d。观察两组患者的临床疗效及有无出血、药物过敏等不良反应。结果两组患者的临床疗效间差异有非常显著性意义（P〈0．01）。治疗组患者治疗前、后血浆黏度、全血黏度低切间差异均有显著性意义（P〈0．05），且无严重不良反应。结论低分子肝素钙治疗肺心病急性发作期安全有效。     

非心脏手术围术期的桥接抗凝治疗

长期给予维生素K拮抗剂抗凝治疗的患者在行外科手术或行有创性操作时面临着出血风险,而在围术期停用维生素K拮抗剂又可能增加血栓栓塞风险。使用治疗剂量肝素类药物的桥接抗凝治疗后可避免围术期暂时中断维生素K拮抗剂治疗所致的血栓栓塞事件。本文对此进行有关讨论。     

Periprocedural management of anticoagulation for atrial fibrillation catheter ablation in direct oral anticoagulant–treated patients

Background

Guidelines recommend performing atrial fibrillation (AF) catheter ablation without interruption of a direct oral anticoagulants (DOACs) and to administer unfractionated heparin (UFH) for an activated clotting time (ACT) ≥300 seconds, by analogy with vitamin K antagonist (VKA). Nevertheless, pharmacological differences between DOACs and VKA, especially regarding ACT sensitivity and UFH response, prevent extrapolation from VKA to DOACs.

Hypothesis

The level of anticoagulation at the time of the procedure in uninterrupted DOAC–treated patients is unpredictable and would complicate intraprocedural UFH administration and monitoring.

Methods

This prospective study included interrupted DOAC–treated patients requiring AF ablation. Preprocedural DOAC concentration ([DOAC]), intraprocedural UFH administration, and ACT values were recorded. A cohort of DOAC‐treated patients requiring flutter catheter ablation was considered to illustrate [DOAC] without DOAC interruption.

Results

Forty‐eight patients underwent AF and 14 patients underwent flutter ablation, respectively. In uninterrupted DOAC–treated patients, [DOAC] ranged from ≤30 to 466 ng/mL. When DOAC were interrupted, from 54 to 218 hours, [DOAC] were minimal (maximum: 36 ng/mL), preventing DOAC‐ACT interference. Anyway, ACT values were poorly correlated with UFH doses (R ² = 0.2256).

Conclusions

Our data showed that uninterrupted DOAC therapy resulted in an unpredictable and highly variable initial level of anticoagulation before catheter ablation. Moreover, even with DOAC interruption preventing interference between DOAC, UFH, and ACT, intraprocedural UFH monitoring was complex. Altogether, our exploratory results call into question the appropriateness of transposing UFH dose protocols, as well as the relevance of ACT monitoring in uninterrupted DOAC–treated patients.     

早期那屈肝素预防脑出血患者深静脉血栓形成的安全性

目的 评价自发性脑出血(spontaneous intracerebral hemorrhage,sICH)患者早期皮下注射小剂量低分子肝素(low molecular weight heparin,LMWH)那屈肝素预防深静脉血栓形成(deep vein thrombosis,DVT)的安全性.方法 纳入早期使用那屈肝素或下肢间歇式充气加压装置(intermittent pneumatic compression,IPC)预防DVT的急性sICH患者.那屈肝素组从入院后第4天开始连续10 d皮下注射那屈肝素0.4 ml/d,IPC组使用IPC治疗.入院后第3天、第5天和第14天复查头颅CT评估血肿体积变化,记录治疗过程中的出血事件,彩色多普勒超声检查下肢DVT.结果 共纳入早期使用那屈肝素或IPC预防DVT的急性sICH患者94例,那屈肝素组41例,IPC组53例.共有14例发生下肢DVT,其中那屈肝素组5例(12.2％),IPC组9例(17.0％),但2组DVT发生率差异无统计学意义(x2 =0.418,P=0.518).治疗期间所有患者均未出现颅内血肿增大和再出血.结论 sICH患者早期皮下注射小剂量那屈肝素预防DVT是安全的.