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.     

A low molecular weight heparin in hemodialysis

Summary The purpose of our study was to check whether the dosage recommended for the low molecular weight heparin tested here, i.e., 50% of the corresponding unfractionated heparin dose, is adequate to prevent clot formation in the extracorporeal system. Sixteen dialysis treatments of 4–5 h were given to each of six chronic dialysis patients. In dialyses 1, 2, 15 and 16 unfractionated heparin (initial dose 35 IU/kg, continuous dose 20 IU/kg/h) was given, and in dialyses 3–14 low molecular weight heparin (initial dose 17.5 anti-Xa U/kg, continuous dose 10 anti-X U/kg/h). At these dose levels of low molecular weight heparin, clot formation occurred in the extracorporeal system in five of the six patients, despite the fact that the plasma anti-Xa level of 0.5 U/ml recommended by the manufacturer had been attained. For this reason the continuous dose of low molecular weight heparin had to be raised to approx. 80% of the corresponding continuous dose of unfractionated heparin. A plasma anti-Xa level of 0.7 U/ml is necessary to prevent extracorporeal clot formation.Abbreviations anti-Xa U Anti-factor Xa unit - aPTT Activated partial thromboplastin time - AT III Antithrombin III - IU International unit - LMWH Low molecular weight heparin - UFH Unfractionated heparin     

Does calcium balanced heparin affect blood gas and electrolyte analysis?

The effect of calcium-balanced heparin (471896, CIBA CORNING) on blood gas and electrolyte analysis was evaluated, by comparing with that of sodium heparin (Na heparin). One ml of whole blood was collected into a syringe, which contained calcium-balance heparin (Ca balanced heparin) or Na heparin. 122 pairs of blood samples obtained from 15 patients were analyzed for Na, K, ionized calcium (Ca(++)), total hemoglobin, pH, P(CO)(2), and P(O)(2) by an automatic blood gas and electrolyte analyzer, CIBA CORNING model 288. There was a significant difference ( P < 0.05) in pH, P(CO)(2), Na, and Ca(++) between the two different groups. Ca(++) concentration was significantly less in Na heparin group than in Ca balanced heparin group, probably due to more chelation of Ca(++) by Na heparin than Ca balanced heparin. The present study suggests that the Ca balanced heparin has minimal effect on the blood gas and electrolyte analysis, and is a suitable anticoagulant for the Ca(++) measurement.     

Further studies of the turnover of dog antithrombin III. Study of 131I-labelled antithrombin protease complexes

Fresh plasma containing 131I-antithrombin III (*I-AT) was coagulated and incubated at 37 degrees C for 2 hr. A "complex peak," separated on heparin-agarose contained AT and *I-AT antigen but no heparin cofactor activity. Crossed immunoelectrophoresis showed only AT complexes. SDS PAGE showed 80% of the *I-AT in a major band (approximately 80,000 daltons), 15% in a minor band (approximately 100,000 daltons) and the rest in trace bands (approximately 60,000 and/or 115,000 daltons). Ammonia treatment of the complex peak released alpha-thrombin. After i.v. injection 80% of the complexed *I-AT, chiefly as the major band, left the plasma with t 1/2 approximately 15 min and was almost immediately catabolized to low molecular weight breakdown products. A major catabolic site was the liver. A simple kinetic model describes the findings approximately.     

降纤酶低分子肝素治疗短暂性脑缺血发作的研究

目的 观察降纤酶与低分子肝素治疗短暂性脑缺血发作的效果及副作用。方法 选择本院神经内科住院患者36例应用降纤酶10U加入加入250ml生理盐水中静脉滴注，隔日1次，共3次；低分子肝素0．5ml脐旁皮下注射，12h 1次，连用7—10d,同时常规给予复方丹参滴注，口服尼莫地平，维生素E，维生素C，停用低分了肝素后给予肠溶阿斯匹林75mg，每日1次口服。结果 治疗开始后TLA发作相继减少，停止发作时间分别为1d内9例，3d内15例，5d内12例。随访6个月—1年，1例2个月后复发，重新应用上药治愈。结论 降纤酶与低分子肝素治疗TLA安全有效、无明显副作用、不易复发。     

微量肝素对重度窒息并发SIRS新生儿的干预作用

目的探讨微小剂量肝素降低新生儿重度窒息并发全身炎症反应综合征(SIRS)的作用和机制,并观察其副作用。方法对我科2001年1月～2005年10月间94例重度窒息新生儿(不含新生早产儿窒息病例)作回顾性分析。治疗组48例,常规综合治疗基础上加用低分子肝素钠5U/(kg·次),皮下注射,每12h1次,连用3d。对照组46例,采用综合治疗。就组间1周内SIRS的发生率作对照分析。结果治疗组1周内SIRS发生率和对照组间存在比较显著差异(P<0.05〉,而新生儿颅内出血、上消化道出血、和皮下出血的发生情况比较无显著差异性(P均>0.05)。结论早期应用微小剂量肝素可有效降低重度窒息新生儿SIRS的发生率而不致增加继发器官出血的机会。     

肝素在治疗妊娠中晚期脐动脉血流异常的临床探讨

目的探讨肝素对妊娠中晚期脐动脉血流异常的影响,以便寻找改善脐动脉血流异常的有效治疗方法。方法采用脐动脉血流收缩期最大血流速度(S)与舒张末期血流速度(D)的比值,将脐动脉血流S/D比值大于相应孕周的第95百分位以上的83例妊娠中晚期妇女共85例胎儿(2例双胎)分为研究组(41例孕妇,42例胎儿)和对照组(42例孕妇,43例胎儿)。研究组应用肝素6 250 u+5%葡萄糖500 mL;对照组应用低分子右旋糖酐500 mL,丹参30 mL+10%葡萄糖500 mL。定期复查脐动脉血流S/D比值(每天1次)。结果研究组平均每天脐动脉血流S/D比值下降0.39,对照组平均每天脐动脉血流S/D比值下降0.12,两组结果比较差异具有显著性(t=3.45,P<0.05)。研究组所需治疗时间显著短于对照组(3.5±2.7 vs 7.3±3.1d),两组比较差异具有显著性(t=5.83,P<0.01)。研究组脐动脉血流S/D比值下降率为100%,对照组为68.3%,两组比较差异有统计学意义(χ2=4.12,P<0.05)。结论肝素可显著改善妊娠中晚期脐动脉血流异常,效果显著,疗程缩短,值得推广。     

2019—2021年复旦大学附属妇产科医院低分子肝素的使用合理性分析

目的 分析2019—2021年复旦大学附属妇产科医院住院患者低分子肝素的使用情况，并评价其合理性，为妇产科低分子肝素合理性使用提供数据资料。方法 采用回顾性研究方法，从复旦大学附属妇产科医院住院医院信息系统（HIS）中查询2019年1月—2021年12月使用低分子肝素的病史信息，包含患者年龄、科室、出入院诊断、手术名称、药品名称及规格、使用频次、单次剂量和给药途径等。结果 2019—2021年使用低分子肝素的患者共54 138例，其中产科14 068例，妇科40 070例。产科年龄分布在19～35岁，妇科年龄分布在41～60岁。诊断为静脉血栓栓塞的患者共102例，妇科患者居多，占比90.20%。预防用药方面，产科剖宫产患者居多，占比63.25%；妇科为手术患者，占比98.06%，妇科恶性肿瘤的患者占比26.28%。产科及妇科患者预防用药和治疗性用药疗程主要集中在1～7 d，不合理的用法用量主要表现为给药途径不合理、单次剂量超限和给药频次不合理等，共64例，占比0.12%。结论 2019—2021年复旦大学附属妇产科医院低分子肝素的使用以预防使用为主。产科以剖宫产患者为主，妇科以手术患者为主，用法用量基本合理。     

The toxicology of heparin reversal with protamine: past,present and future

Introduction: Unfractionated heparin is a strongly anionic anticoagulant used extensively in medicine to prevent blood clotting. In the case of an emergency bleeding in response to heparin, the protamine sulfate is administered. Despite its extensive clinical use, protamine may produce life-threatening side effects such as systemic hypotension, catastrophic pulmonary vasoconstriction or allergic reactions. Recent studies have demonstrated new organ-specific complications of the heparin reversal with protamine.

Areas covered: Past and present knowledge of the mechanisms responsible for the toxicity of protamine and the most promising potential replacements of protamine in the different phases of development.

Expert opinion: Despite of the low therapeutic index, protamine is the only registered antidote of heparins. The toxicology of protamine depends on a complex interaction of the high molecular weight, a cationic peptide with the surfaces of the vasculature and blood cells. The mechanisms involve membrane receptors and ion channels targeted by different vasoactive compounds, such as nitric oxide, bradykinin or histamine. Unacceptable side effects of protamine have led to a search for new alternatives: UHRA, LMWP, and Dex40-GTMAC3 are in the preclinical stage; the two other agents (andexanet alfa and PER977) are already in the advanced clinical phases.     

低分子肝素联合奥扎格雷钠治疗急性脑梗死疗效评价

目的评价低分子肝素联合奥扎格雷钠治疗急性脑梗死的有效性及安全性。方法将96例符合诊断标准的急性脑梗死患者随机分成3组,每组32例,分别给予低分子肝素联合奥扎格雷钠(联合组)治疗,并与单纯应用低分子肝素(低分子肝素组)和单纯应用奥扎格雷钠(奥扎格雷钠组)治疗的患者进行临床疗效、治疗前后神经功能缺损程度评分(NDS)的比较。结果治疗后联合组显效率(75%)明显优于低分子肝素组(31.3%)及奥扎格雷钠组(34.4%),NDS减分程度与低分子肝素组及奥扎格雷钠组相比,差异均有统计学意义(P<0.05,P<0.01)。结论低分子肝素联合奥扎格雷钠治疗急性脑梗死疗效显著并且安全可靠。