直接Xa因子抑制剂预防全膝关节置换后深静脉血栓的Meta分析

背景：直接Xa因子抑制剂开始在预防和治疗血栓方面发挥重要作用,与低分子量肝素相比其在预防全膝关节置换后血栓形成中的疗效与安全性尚不清楚。 目的：探讨直接Xa因子抑制剂和低分子量肝素预防全膝关节置换后深静脉血栓的优劣。 方法：电子检索MEDLINE,EMBASE,Cochrane图书馆、CBM,CNKI等数据库,并辅以手工检索,全面查找国内外比较直接Xa因子抑制剂和低分子量肝素预防全膝关节置换后深静脉血栓的随机对照试验。根据Cochrane手册提出的文献质量评价标准对纳入研究进行质量评价,并应用统计软件Stata12.0进行数据分析。 结果与结论：直接Xa因子抑制剂较低分子量肝素可显著降低全膝关节置换患者症状性深静脉血栓发生率(P < 0.05),且不增加出血风险,2组患者肺栓塞和随访期内死亡率差异无显著性意义(P > 0.05)。提示在全膝关节置换后深静脉血栓的预防中,直接Xa因子抑制剂较低分子量肝素更加安全、有效和方便。     

Modified Dendrimer Cross-Linked Collagen-Based Matrices

Abstract

Dendrimer cross-linking has been achieved with pepsin digested over 80% type-I bovine collagen to create strong hydrogels with good cell compatibility. Herein we investigate the use of commercially available collagen-based products with the dendrimer cross-linking technology. Specifically PureCol^® (PC), a 97% bovine type-I collagen, human collagen (HC) and human extracellular matrix (hECM) were concentrated, and then cross-linked with polypropyleneimine octaamine generation two dendrimers using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) chemistry. PC gels with 30 and 20 mg/ml bovine collagen were fabricated, and despite similar concentrations to >80% type-I bovine collagen dendrimer cross-linked gels (CG), PC gels demonstrated increased swelling and decreased stability, as determined with collagenase digestion. The highly purified bovine (PC) and human sourced-collagen (HC) gels were similar in performance, but not as stable as the CG gels, which may correlate to the manufacturer’s collagen purification and storage. Finally, the addition of hECM components to PC to create PC-hECM gels, resulted in a looser gel network, compared to heparinized dendrimer cross- linked bovine >80% type-I collagen gels (CHG). However, all collagen-based gels supported 3T3 fibroblast cell growth over 4 days, indicating these gels may be suitable for tissue-engineering applications.     

Optimal Anticoagulation during Off Pump Coronary Artery Bypass in Patients Recently Exposed to Clopidogrel

Purpose

The aim of this study was to find an optimal range of activated clotting time (ACT) during off-pump coronary artery bypass surgery (OPCAB) yielding ischemic protection without the risk of hemorrhagic complications in patients with recent exposure to dual antiplatelet therapy.

Materials and Methods

Three hundred and five patients who received aspirin and clopidogrel within 7 days of isolated multi-vessel OPCAB were retrospectively studied. Combined hemorrhagic and ischemic outcome was defined as the occurrence of 1 of the following: significant perioperative bleeding (>30% of estimated blood volume), transfusion of packed red blood cell (pRBC) ≥2 U, or myocardial infarction (MI). This was compared in relation to the tertile distribution of the time-weighted average ACT-212-291 sec (first tertile), 292-334 sec (second tertile), 335-485 sec (third tertile).

Results

The amount of perioperative blood loss was 937±313 mL, 1014±340 mL, and 1076±383 mL, respectively (p=0.022). Significantly more patients in the third tertile developed MI (4%, 4%, and 12%, respectively, p=0.034). The incidence of significant perioperative blood loss and transfusion of pRBC ≥2 U were lower in the first tertile than those of other tertiles without statistical significance. In the multivariate analysis, the first tertile was associated with a 52% risk reduction of combined hemorrhagic and ischemic outcomes (95% confidence interval: 0.25-0.92, p=0.027).

Conclusion

A lower degree of anticoagulation with a reduced initial heparin loading dose should be carefully considered for patients undergoing OPCAB who have recently been exposed to clopidogrel.     

低分子肝素钙预防腰椎退行性疾病术后深静脉血栓形成的有效性和安全性

目的探讨低分子肝素钙预防腰椎退行性疾病术后深静脉血栓形成(DVT)的有效性和安全性。方法回顾性分析广安市广安区人民医院68例腰椎退行性疾病患者的临床资料,术后均采用抗凝预防血栓形成,按照术后预防DVT所采用方式的不同分为对照组和低分子肝素钙组。分析比较2组患者术后引流量、切口愈合情况、DVT发生率、皮下瘀斑情况、血小板数值、凝血功能、D-二聚体。结果术后2组患者引流量、切口愈合情况、皮下瘀斑情况、凝血功能相关指标比较,差异无统计学意义(P>0.05)。术前和术后1、10 d 2组患者血小板数量的变化差异无统计学意义(P>0.05)。DVT发生率2组患者比较差异有统计学意义(P<0.05)。术前及术后1 d 2组患者D-二聚体比较,差异无统计学意义(P>0.05);术后10 d,对照组患者D-二聚体显著增加,2组比较差异有统计学意义(P<0.05)。结论腰椎退行性疾病术后使用低分子肝素钙进行抗凝,可以显著降低DVT的发生率,具有良好的安全性。     

肝素涂层体外循环管道抗凝血性能的研究

目的 评测3种离子键肝素涂层体外循环管道的抗凝血性能和稳定性。方法 用PT和APTT对不同浓度肝素—氯烃基二甲基代苯甲胺(HBC)复合物涂层体外循环管道的凝血性能进行评测，同时测试体外转流对3种肝素涂层管道抗凝血性能的影响。结果 3种肝素涂层方法均能够将肝素分子结合于材料表面并具有抗凝活性，其中HBC复合物和肝素—聚乙烯亚胺复合物处理的体外循环管道经体外转流96h后仍具有较佳的抗凝血活性。结论 离子键肝素涂层因结合物质不同其稳定性也不同；HBC复合物和肝素—聚乙烯亚胺复合物处理的体外循环管道肝素分子结合较牢固，能够满足临床短期使用需要。     

凝血酶激活的纤溶抑制物: 新的凝血纤溶调控因子

凝血酶激活的纤溶抑制物(Thrombin—activatable fibrinolysis inhibitor，简称TAFI)，作为凝血及纤溶调控因子，是近十年来国外医学界研究的热点之一；TAFI的基础研究是对经典凝血及纤溶调控机制的重要补充；在体内主要由凝血酶、凝血酶调节蛋白、纤溶酶、肝素、胰蛋白酶等物质激活而导致纤溶机制受抑，血栓溶解时间延长，从而增加血栓形成的危险性。TAFI在体内还参与缓激肽、补体等活性物质的调节。动物血栓模型运用TAFI拮抗剂与溶栓剂联合治疗，取得良好效果。国外医学界对TAFI与血液、心血管、内分泌等系统疾病的发病关系已展开广泛研究。     

The role of low molecular weight heparin on recurrent pregnancy loss: A systematic review and meta-analysis

To assess the roles of the low molecular weight heparin (LMWH) on recurrent pregnancy loss (RPL). The relevant studies of all randomized controlled trials (RCTs) were retrieved, and the systematic evaluation was conducted. PubMed, Embase, and Cochrane library databases were searched by using keywords, including low-molecular-weight heparin or LMWH, and recurrent miscarriage or recurrent pregnancy loss in pregnant women from their earliest data to February 2020. Two investigators independently evaluated eligibility. Risk ratios (RRs) and their corresponding 95% confidence interval (CI) were determined. To pool the results, this meta-analysis was performed using random-effect model due to the high heterogeneity among these eight studies. A total of eight RCTs involving 1854 participants were included in the meta-analysis involving 963 patients with RPL who were prescribed LMWH (enoxaparin, tinzaparin, or dalteparin) alone and 891 patients who were treated with no LMWH interventions (placebo, folic acid or non-treatment) were compared. Pooled data from the remaining eight RCTs showed the differences between intervention groups and control groups. Compared with control groups, LMWH had significantly improved live births (RR,1.19; 95%CI, 1.03 to 1.38; P = 0.02), and reduced miscarriage rates (RR, 0.62; 95%CI, 0.43 to 0.91; P = 0.01). The study suggested that LMWH could improve the live births and reduce the miscarriage rates of RPL. Therefore, LMWH might be a good treatment choice for women with unexplained PRL.     

心脏机械瓣膜置换术后妊娠期两种抗凝方案疗效Meta分析

目的 评价全程使用维生素K拮抗剂（VKA）的抗凝方案与妊娠早期短程使用低分子肝素/肝素的方案应用于心脏机械瓣膜置换术患者妊娠期的有效性与安全性。方法 通过多种途径检索截止至2013年10月关于两种抗凝方案比较的研究,后进行Meta分析。结果 纳入的10项研究分析结果显示全程使用VKA的抗凝方案较之妊娠早期短程使用低分子肝素/肝素的方案：（1）母体栓塞事件发生率明显降低（OR：0.33,95%CI：0.19~0.57,P<0.0001）。（2）胎儿流失发生率增加56%（OR：1.56,95%CI：1.11~2.20,P=0.0106）。（3）胎儿早产、低出生体重儿发生率稍增加。结论 心脏机械瓣膜置换术孕妇抗凝方案应根据栓塞风险、经济情况、治疗依从性等进行选择。     

肝素结合表皮生长因子在顺铂耐药卵巢癌中的表达及相关性研究

目的检测肝素结合表皮生长因子（HB-EGF）在顺铂耐药卵巢癌中的表达水平并探讨HB-EGF与卵巢癌对顺铂耐药性的关系。方法①体外实验：蛋白印迹法检测卵巢癌亲本细胞株A2780和顺铂耐药株A2780/CDDP中HB-EGF蛋白的表达。分别予以HB-EGF抑制剂CRM197治疗,四甲基偶氮唑蓝（MTT）比色法检测细胞的增殖能力,酶标仪检测加药前后caspase-3蛋白的活性;②体内实验：建立A2780组和A2780/CDDP组卵巢癌裸鼠移植瘤模型,免疫组化法检测2组移植瘤中HB-EGF蛋白的表达。分别予以CRM197治疗观察移植瘤的生长情况并计算CRM197抑瘤率。结果体内外实验结果表明,与A2780组相比,HB-EGF在A2780/CDDP组中高表达。CRM197可有效地降低A2780/CDDP细胞的增殖能力和caspase-3的表达,抑制A2780/CDDP组裸鼠移植瘤的生长（P〈0.001）。结论 HB-EGF在顺铂耐药卵巢癌中高表达,并与卵巢癌对顺铂的耐药性相关。