The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P- and L-selectin function in vivo

BACKGROUND: Adhesion molecules of the selectin family (mainly P- and L-selectin) have been suggested to mediate interactions between platelets, leukocytes and endothelial cells in thrombus formation. The polysaccharide fucoidan has anticoagulative properties, but is also able to bind and block the function of the selectins. Here, we investigated in vivo (i) if fucoidan can prevent microvascular thrombus formation, and (ii) whether this is potentially mediated by the inhibition of P-and/or L-selectin. MATERIALS AND METHODS: For this purpose, we used intravital microscopy in the mouse cremaster microcirculation in which thrombosis was induced photochemically by light exposure to individual arterioles and venules after intravenous (i.v.) injection of FITC-dextran. RESULTS: We found that intravenous administration of fucoidan significantly prolonged the time required for complete occlusion in arterioles and venules by almost seven- and nine-fold, respectively. In contrast, treatment with monoclonal antibodies against P- and L-selectin had no effect on the development of microvascular thrombosis. Fucoidan and also the anti-P-selectin antibody completely inhibited baseline venular leukocyte rolling in the cremaster muscle, indicating that these treatment regimes abolished P-selectin function. Importantly, fucoidan and the anti-P-selectin antibody had no effect on systemic platelet and leukocyte counts. On the other hand, we found that fucoidan treatment significantly altered coagulation parameters, including prothrombin time (Quick percentage), activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), which may explain the potent in vivo anticoagulative effect of fucoidan observed here. CONCLUSIONS: Taken together, our novel findings suggest that fucoidan effectively prevents microvascular thrombus formation induced by endothelial damage in arterioles and venules in vivo. This protective effect of fucoidan is not attributable to inhibition of P- and L-selectin function but may instead be related to the anticoagulative capacity of fucoidan.     

不同性质海洋硫酸多糖的制备及其改善大鼠脂肪肝作用的比较研究

目的 探索了不同来源、不同分子量的海洋硫酸多糖对脂肪肝大鼠脂肪代谢的调节作用.方法 SD大鼠随机分为7组,正常对照组、脂肪肝模型对照组、0.1%低分子量海参岩藻聚糖硫酸酯组、0.1%海参岩藻聚糖硫酸酯组、0.2%海参岩藻聚糖硫酸酯组、0.2%海藻岩藻聚糖硫酸酯组、0.2%海参硫酸软骨素组,每组6只.饲料中添加1%乳清酸...     

低分子肝素联合舒血宁治疗伴颈动脉斑块的脑梗死临床研究

目的：观察低分子肝素治疗脑梗死和颈动脉斑块的疗效和安全性,并对不同剂量作对比研究。方法：伴颈动脉粥样斑块的急性脑梗死患者150例,随机分为3组：低分子肝素钙注射液大剂量组、低分子肝素小剂量钙注射液组和对照组,各50例。对照组予生理盐水250mL＋舒血宁20mL,静滴,qd,疗程14d。大剂量组在对照组治疗的基础上予低分子肝素钙注射液1mL,5000AXaIU,皮下注射,每日2次,连用14d。小剂量组在对照组治疗的基础上予低分子肝素钙注射液1mL,5000AXaIU,皮下注射,每日1次,连用14d。结果：舒血宁、大剂量低分子肝素或小剂量低分子肝素联合舒血宁均能显著缩小颈动脉粥样硬化斑块（P〈0.01）,且大剂量低分子肝素联合舒血宁对脑梗死的疗效优于小剂量低分子肝素联合舒血宁组,小剂量低分子肝素联合舒血宁组的疗效优于单纯舒血宁治疗组治疗组,大剂量低分子肝素联合舒血宁较剂量低分子肝素联合舒血宁组或单纯舒血宁治疗组显著减少脑梗死的复发。低分子肝素联合舒血宁治疗中,未见严重出血情况。结论：大剂量低分子肝素钙注射液联合舒血宁治疗脑梗死和颈动脉粥样硬化疗效肯定,且能减少脑梗死的复发,无严重副作用。     

海带中褐藻糖胶的超声提取工艺的优化

目的研究以水为溶剂超声波强化提取海带褐藻糖胶的工艺。方法采用正交设计,以超声提取时间、超声功率、固液比和提取温度为考察因素,优选了超声波提取海带中褐藻糖胶的最佳工艺。结果各因素对提取率的影响大小依次为：超声提取时间〉固液比〉提取温度〉超声功率,优选的最佳提取工艺为：超声作用时间30 min,固液比1∶30,提取温度40℃,超声功率320 W。按此条件重复实验3次,测得褐藻糖胶的提取量为19.89 mg.g-1。结论较之传统提取方法,超声法提取海带中褐藻糖胶具有省时、节能等优点。     

Adherence to Pharmacological Thromboprophylaxis Orders in Hospitalized Patients

Objective

We compared adherence to unfractionated heparin (UFH) 2 or 3 times daily prophylaxis orders versus low-molecular-weight heparin (LMWH) once daily orders. Our goals were to determine which strategy demonstrated the best adherence in terms of timing and frequency of dose administration, and to determine reasons for ordered heparin not being administered.

Methods

We queried our electronic medication administration record where nurses document reasons for delayed administration or omitted doses. We identified 250 consecutive patients who were prescribed prophylaxis with UFH 2 or 3 times daily or LMWH once daily. We followed patients for their hospitalization to determine adherence to physicians' prophylaxis orders.

Results

Adherence, defined as the ratio of prophylaxis doses given to doses ordered, was greater with LMWH (94.9%) than UFH 3 times daily (87.8%) or UFH twice daily (86.8%) regimens (P <.001). Patients receiving LMWH more often received all of their scheduled prophylaxis doses (77%) versus UFH 3 times daily (54%) or UFH twice daily (45%) (P <.001). There were no differences between regimens regarding reasons for omitted doses. The most common reason for late or omitted doses was patient refusal, which explained 44% of the UFH and 39% of the LMWH orders that were not administered.

Conclusions

LMWH once a day had better adherence than UFH 2 or 3 times daily. For both LMWH and UFH, patient refusal was the most common reason for not administering prophylaxis as prescribed. These findings require consideration when evaluating pharmacological prophylaxis strategies. Educational programs, explaining the rationale, may motivate patients to improve adherence during hospitalization.     

Submucosal hematoma presenting as small bowel obturator obstruction in a patient on low-molecular-weight heparin

Recent studies have shown the efficacy of low-molecular-weight heparin (LMWH) in the treatment of venous thromboembolic disease in children. Compared to unfractionated heparin and coumadin, LMWH has more predictable pharmacokinetics and a reported lower incidence of osteoporosis and heparin-induced thrombocytopenia in children. The overall incidence of severe hemorrhage on LMWH in children is low. To date, there is a single report of a small bowel obstruction in a child secondary to a hematoma while on LMWH. We report the second case of a child, on enoxaparin (Lovenox) therapy, who underwent bowel resection secondary to a completely obstructing small bowel wall hematoma.     

低分子肝素治疗难治性肾病综合征临床疗效观察

目的　观察低分子肝素 (LMWH)治疗难治性肾病综合征临床疗效、抗凝效果及安全性。方法　 3 3例伴高凝状态的原发性肾病综合征患者随机分为两组 ,对照组予强的松 1mg/kg/天 +环磷酰胺 5 0mgBid口服 +甲基强的松龙 0 5～ 1g(2 0mg/kg/次 )加入 5 %葡萄糖液 2 5 0ml静脉点滴 ,治疗组在对照组治疗方案基础上加LMWH5 0 0 0IU皮下注射每天两次 ,共观察 4周 ,治疗前后均观察临床症状体征及 2 4h尿蛋白定量和肾功能的变化 ,并检测血浆抗凝血酶Ⅲ (AT -Ⅲ )活性、血纤维蛋白原 (FIB)、D -二聚体 (DD)、血浆因子Xa因子 (FXa)活性、血浆因子IIa(FIIa)活性。结果　治疗 4周后两组患者 2 4小时尿总蛋白、尿素氮 (BUN)、血肌酐 (Cr)明显下降 (P <0 0 5 ) ,血清白蛋白 (ALB)、内生肌酐清除率 (Ccr)明显升高 (P <0 0 5 ) ,但治疗组中 2 4h尿总蛋白下降显著大于对照组(P <0 0 5 ) ,血清白蛋白上升显著高于对照组 (P <0 0 5 ) ,治疗组治愈率和显效率明显高于对照组 (P <0 0 5 ) ,无效率明显低于对照组 (P <0 0 5 )。治疗组中AT -III活性明显升高 (P <0 0 5 ) ,FIB、DD、FXa活性明显降低 (P <0 0 5 ) ,FIIa无明显变化 ,无一例并发深静脉血栓形成 ,对照组中上述指标无明显变化 ,且 4例出现深静脉血栓形成。结论　在     

低分子肝素预处理对髋关节置换中骨水泥填充后凝血指标改变的影响

目的探讨髋关节置换术中填充骨水泥时用低分子肝素预处理对患者的凝血机制的影响。方法老年股骨颈骨折患者行人工关节置换术患者60例,随机分为两组,对照组股骨颈骨折行人工关节置换术前未预先用药;实验组股骨颈骨折在行人工关节置换术前12小时皮下给予常规剂量低分子肝素注射。观察两组在填充骨水泥前后PT、APTT、FIB、TT及D-二聚体的变化。结果对照组在填充骨水泥前后PT缩短,FIB和D-二聚体在注入骨水泥后增多,APTT及TT在骨水泥注入前后变化不明显。实验组中在填充骨水泥前后PT、APTT、TT及FIB变化不明显,D-二聚体增多。结论骨水泥充填前用低分子肝素预处理,可以明显减少凝血指标的波动,减少血管内凝血发生的机会,对早期深静脉血栓的形成有预防作用。     

Significance of Decreased Plasma D-Dimer Levels following Lipopolysaccharide-Induced Disseminated Intravascular Coagulation in Rats

Plasma D-dimer (DD) is considered to be one of the most useful markers in the diagnosis and assessment of disseminated intravascular coagulation (DIC). The present study was performed to clarify the role of DD in a rat model of lipopolysaccharide (LPS)-induced DIC in which low-molecular-weight heparin (LMWH) and tranexamic acid (TA) were used. We investigated whether a relationship exists between plasma DD levels and severity of DIC. Experimental DIC was induced in rats by a sustained 4-hour infusion of 30 mg/kg LPS administered via the tail vein (LPS group). Rats received either LPS alone (LPS group) or LPS combined with 200 U/kg LMWH (LPS+LMWH group) or 50 mg/kg TA (LPS+TA group) from -30 minutes to 4 hours. Blood was drawn from each rat at 4, 8, and 12 hours. Plasma levels of thrombin-antithrombin complex (TAT) and creatinine were suppressed in the LPS+LMWH group, and less glomerular fibrin deposition was observed compared with the LPS group. On the other hand, an increased level of creatinine and increased glomerular fibrin deposition were observed in the LPS+TA group compared with the LPS group. LMWH demonstrated a protective effect against LPS-induced DIC, resulting in increased survival at 12 hours, whereas TA had the opposite effect. From these results, it appears that LMWH protects against LPS-induced DIC, but TA exacerbates LPS-induced DIC. It was interesting that plasma levels of DD were almost completely suppressed by concurrent administration of either TA or LMWH in this LPS-induced DIC model. This finding suggested that plasma levels of DD were suppressed by inhibition of coagulation (reduced deposition of fibrin) in the LPS+LMWH group and that DD levels were also suppressed by inhibition of fibrinolysis (reduced degradation of fibrin by plasmin) in the LPS+TA group. Thus care should be taken when evaluating the significance of plasma DD levels, because suppressed levels can occur with progressive fibrin deposition and worsening organ dysfunction or improvement in the course of DIC.     

低分子肝素治疗早发型子痫前期及预防再发的系统评价

目的 评价低分子肝素治疗早发型子痫前期及预防再发的疗效和安全性.方法 应用RevMan 4.2软件对检索的15项随机对照试验研究进行统计学分析.结果 联合使用低分子肝素能明显延长孕周时间(WMD=4.50,95％CI:3.27～5.72,P＜0.00001),并降低围生儿死亡率(WMD=0.35,95％CI:0.19～0.67,P=0.001);降低新生儿窒息率(WMD=0.34,95％ CI:0.17～0.69,P=0.003);不增加产后出血量(WMD=-2.22,95％CI:-14.33～9.9,P=0.72),提示肝素对产后出血量无影响;且不增加胎盘早剥的发生(WMD=0.31,95％CI:0.05～2.08,P=0.23),早发型子痫前期再度发生的相对危险度、相对危险降低率均降低(RR=0.12,P=0.04,95％ CI:0.02～0.91,RRR为88.3％).结论 联合低分子肝素治疗早发型子痫前期可以延长孕周时间,降低围生儿死亡及新生儿窒息率,且不增加产后出血及胎盘早剥的发生,是预防早发型子痫前期发生的保护因素.