Low molecular weight heparin (CY-216) versus unfractionated heparin in chronic hemodialysis.

In 14 patients undergoing chronic hemodialysis, we investigated the safety and efficacy of the low molecular fragment (CY-216) in comparison to unfractionated heparin (UFH) in the prevention of clotting in the extracorporeal circuit (ECC). In this study, 168 hemodialysis sessions were undertaken with UFH in 2 bolus doses (5,437 +/- 1,477 SD IU) and 231 with CY-216 in a single bolus dose [initial dose 150 anti-Xa U Institut Choay (IC)/kg]. There were no clots in the bubble trap in any UFH sessions, and 14.8% had coagulated fibers in the dialyzer. Clotting in the bubble trap was observed in 2 CY-216 sessions (0.8%) and coagulated fibers in 22.6% of the sessions. At the end of the study, the mean dose of CY-216 was 250 anti-Xa UIC/kg but a dose of 350 anti-Xa UIC/kg was needed in the 2 patients treated by recombinant human erythropoietin. Anti-Xa levels at the end of the runs were higher (0.47 +/- 0.1 U/ml) in the CY-216 group than in the UFH group (0.28 +/- 0.1 U/ml). There was a correlation between anti-Xa levels and efficacy in the CY-216 group. An anti-Xa activity above 0.4 U/ml was needed in order to minimize thrombus formation. Antithrombin III-protease complexes (ATM) and D dimer fibrin derivatives (D dimer) were used as thrombotic markers but they were of little value for the detection of fibrin formation in the ECC. Our findings suggest that CY-216 administered as a single bolus dose seems to be of similar effectiveness to UFH.     

Future alternatives to heparin: low-molecular-weight heparin and hirudin.

The antithrombotic effects of standard heparin were compared with those of low-molecular-weight heparin (LMWH) and hirudin by use of an in vitro perfusion system. Fresh blood collected from human volunteers was treated with varying doses of these three agents and perfused in a recirculating system over everted porcine vein segments. A low shear rate (100/sec) was selected to simulate conditions in large arteries and veins. Platelet and fibrinogen deposition were evaluated with indium 111 and iodine 125 radiolabels, respectively. Anticoagulant activity was assessed by measuring the activated clotting time (ACT). Anti-Xa activity was assayed to determine the degree to which these agents used antithrombin III pathways. Low-molecular-weight heparin was the weakest anticoagulant, requiring 32 micrograms/ml blood to double the ACT. By contrast, the ACT doubled with only 0.75 and 1.10 micrograms/ml blood of heparin and hirudin, respectively. Heparin and hirudin inhibited platelet and fibrin deposition at equivalent doses. Low-molecular-weight heparin was a less potent inhibitor of fibrin than heparin or hirudin. Hirudin, a direct thrombin inhibitor, exhibited minimal anti-Xa activity, contrasted with 0.14 anti-Xa units/micrograms for LMWH and 0.13 anti-Xa units/mg for heparin. These data suggest that heparin and hirudin are more potent anticoagulants and antiplatelet agents than LMWH.     

Measurement of whole blood factor Xa-activated clotting time during hemodialysis with low-molecular-weight heparin

Purpose To determine whole blood factor Xa-activated clotting time (XaACT), a test for monitoring low-molecular-weight heparins (LMWHs). Methods Blood was obtained from six healthy volunteers. Dalteparin, a LMWH, was mixed with the blood to concentrations of 0,05 and 1.0IU·ml⁻¹. XaACT, activated clotting time (ACT), and activated partial thromboplastin time (APTT) were measured at each dalteparin concentration. XaACT of blood from the outflow and inflow sides of the blood circuit in seven hemodialysis patients was measured before and after bolus administration of 1000 IU of dalteparin, followed by continuous infusion at a rate of 500IU·h⁻¹. Results XaACT, ACT, and APTT in dalteparin-containing blood from volunteers were correlated with dalteparin concentration (y=312.8x+86.4;r ²=0.88;P<0.001,y=41.8x +113.5;r ²=0.83;P<0.001, andy=59.5x+38.8;r ²=0.80;P<0.001, respectively). The regression slope of XaACT was steeper than those of ACT and APTT (P<0.001). In hemodialysis patients, dalteparin increased XaACT on the outflow and inflow sides of the circuit (P<0.001,P<0.05, respectively). Conclusion The measurement of XaACT can be employed to monitor LMWHs in clinical settings.     

Preventing hemorrhage in high-risk hemodialysis: regional versus low-dose heparin

Hemodialysis in patients with increased risk for hemorrhage can be accomplished with either a regional or a low, total dose of heparin. In a prospective study of 69 series of dialyses performed on an alternating schedule of heparinization for each patient, bleeding complications during and immediately following dialysis occurred in 23 of 122 dialyses (19%) with regional heparin compared to 13 of 133 dialyses (10%) with low-dose heparin (P less than 0.05). The incidence of hemorrhage correlated with the estimated degree of bleeding risk both at expected and at occult bleeding sites, and was the same or higher with regional heparin in all categories. Hemorrhage was not correlated with preexisting coagulation abnormalities, concurrent anticoagulant drugs, level of azotemia, or ability to successfully limit systemic heparinization during dialysis. The incidence of partial clotting of the dialyzer was 3 to 5% with both heparin protocols. We conclude that regional heparinization has no clinical or practical advantage over low-total-dose heparin in preventing bleeding associated with hemodialysis.     

Thromboprophylaxis by low-molecular-weight heparin in elective hip surgery. A placebo controlled study.

In a double-blind, randomised study of thromboprophylaxis in patients undergoing total hip replacement, we compared a low-molecular-weight heparin with a placebo. Of the 120 patients enrolled, 112 completed the trial; 58 in the treatment group and 54 in the placebo group. Nine (16%) patients in the treatment group and 19 (35%) in the placebo group developed deep venous thrombosis, diagnosed by the 125I-fibrinogen uptake test (p < 0.02). Verification was obtained by phlebography in 86% of the patients. Prolonged surgery increased the risk of thrombosis in the placebo group but not in the treatment group (p < 0.05). There were significantly more cases of deep venous thrombosis in the placebo group during the first four postoperative days (p < 0.02). The groups did not differ with respect to peroperative and postoperative bleeding. Low-molecular-weight heparin offers safe and easily administered thromboprophylaxis in total hip replacement.     

Pharmacokinetics of low-molecular-weight heparin and unfractionated heparin during elective aortobifemoral bypass grafting.

Perioperative monitoring has demonstrated that administration of heparin on an empirical basis is associated with a wide variation in patient response and elimination rate. This problem may be overcome by intervention on the basis of perioperative monitoring or by using forms of heparin with different pharmacokinetic properties. When compared with unfractionated heparin, low-molecular-weight heparin has a higher bioavailability after subcutaneous administration, a linear clearance mechanism with a prolonged half-life, and is at least as effective in preventing postoperative vein thrombosis. Theoretically these characteristics of low-molecular-weight heparin could lead to more predictable levels of heparin activity. In this study we compared the pharmacokinetics of low-molecular-weight heparin and unfractionated heparin after an intravenous injection in patients undergoing aortic graft surgery. Heparin activity was measured before heparin administration and at 5, 20, 35, 50, 65, 80, 95, and 110 minutes after administration. The anti-Xa activity in the low-molecular-weight heparin group showed less variation and was more sustained when compared to the unfractionated heparin group. Fibrin degradation products were moderately correlated with the anti-factor Xa levels of the low-molecular-weight heparin group, but no correlation was found in the unfractionated heparin group. The anti-factor Xa activity of low-molecular-weight heparin was, in contrast to that of unfractionated heparin, not completely reversible by protamine administration. The blood loss was comparable in both groups. In contrast to what was expected, the pharmacokinetic profiles of low-molecular-weight heparin and unfractionated heparin showed a similarity after intravenous injection in patients undergoing aortobifemoral bypass grafting. Factors that could have influenced the pharmacokinetic behavior of heparin are discussed.     

Preoperative dosing of low-molecular-weight heparin in hepatopancreatobiliary surgery

Background

Venous thromboembolism is a common cause of morbidity. Guidelines recommend perioperative thromboprophylaxis, but clinicians remain cautious of bleeding after major oncologic resections.

Methods

Retrospective analysis of a single institution's prospective hepatopancreatobiliary database was performed for patients undergoing surgery between January 2010 and February 2013. A total of 223 patients received postoperative thromboprophylaxis and 93 patients were dosed with low-molecular-weight heparin (LMWH) preoperatively.

Results

Two hundred twenty-three patients were analyzed; 50.6% underwent pancreatic and 49.3% underwent liver resection. There were no differences in previous venous thromboembolism (3.8% vs 3.3%; P = .56) or preoperative venous thromboembolism scores (5.74 vs 5.67; P = .82). Estimated blood loss (537 mL vs 592 mL; P = .54), transfusions (25.4% vs 30.4%; P = .25), and complications (52.3% vs 43.5%; P = .12) were equivalent. Incidence of thromboembolic events was lower (6.1% vs 1.1%; P = .05); however, bleeding requiring intervention was increased in the preoperative LMWH group (10.9% vs 3.1%; P = .026).

Conclusions

Caution must be exercised when using LMWH, as bleeding remains a concern for oncologic hepatopancreatobiliary surgery.     

Acute effect of standard heparin versus low molecular weight heparin on oxidative stress and inflammation in hemodialysis patients

OBJECTIVE: Atherosclerotic cardiovascular diseases caused by traditional and non-traditional risk factors are the most common cause of morbidity and mortality in hemodialysis patients. Recently, much interest has been focused on non-traditional factors, such as oxidative stress, inflammation, and endothelial dysfunction. Hemodialysis patients are not only exposed to oxidative stress but also to inflammation. Although anticoagulants are the most frequently used drugs in hemodialysis patients, their effect upon oxidative stress and inflammation in dialysis patients are still unknown. METHODS: Thirty-three hemodialysis patients were randomized into three groups. Group 1 received standard heparin while group 2 received low molecular weight heparin during the dialysis therapy. Group 3 (control group) did not receive any anticoagulant agent. Investigators were blinded to the therapy. Serum concentrations of oxidative stress and inflammation markers, including C-reactive protein, tumor necrosis factor alpha, superoxide dismutase, and malondialdehyde, were measured before and after dialysis session. RESULTS: The oxidative stress and inflammation markers were significantly increased in groups 1 and 3 (p < 0.05 for each) compared to their baseline values. In contrast, baseline and end-treatment values of the oxidative stress and inflammation markers were comparable in the group 2 (p > 0.05). CONCLUSION: These findings indicate that the type of anticoagulants may take a role in the acute effect of hemodialysis upon oxidative stress and inflammation markers. A comparison of the groups revealed that low molecular weight heparin decreased the oxidative stress and inflammation, whereas standard heparin increased the oxidative stress and inflammation. Low molecular weight heparin appears to have an additive benefit for hemodialysis patients.     

利伐沙班与低分子量肝素在初次全髋关节置换术后深静脉血栓形成防治中的比较研究

目的 通过比较利伐沙班与低分子量肝素(LMWH)在初次全髋关节置换(THA)术后下肢深静脉血栓形成(DVT)防治中的作用,评估利伐沙班的有效性、安全性以及其足疗程应用防治血栓的必要性. 方法 对2008年1月至2010年4月收治的136例单侧初次行THA患者进行回顾性分析,根据术后预防DVT使用药物不同分为利伐沙班组和LMWH组,每组各68例.利伐沙班组男28例,女40例;平均(61.6±10.7)岁,体质量平均(63.9±11.2) kg.LMWH组男31例,女37例;平均(60.3±12.4)岁,体质量平均(65.5±9.8) kg.两组患者治疗前一般资料差异无统计学意义,具有可比性.LMWH组术后应用时间为1周,利伐沙班组术后应用时间分别为2周38例,5周30例.比较分析两组患者应用药物前、后血红蛋白、血小板、凝血功能情况,以及症状DVT发生率、轻微和严重出血事件发生率. 结果 两组患者手术前、后血红蛋白、血小板、凝血功能、轻微和严重出血事件发生率比较差异均无统计学意义(P＞ 0.05),LMWH组症状DVT发生率为7.4％,利伐沙班组为0,两组比较差异有统计学意义(P＜0.05). 结论 与LMWH比较,初次THA术后DVT防治中利伐沙班更安全、有效,足疗程抗凝十分必要.     

A randomised comparison of a foot pump and low-molecular-weight heparin in the prevention of deep-vein thrombosis after total knee replacement

Patients who undergo total knee replacement (TKR) are at high risk of venous thromboembolism. Low-molecular-weight heparins (LMWH) are the most suitable chemical prophylactic agents but there are some uncertainties about their safety and effectiveness. The foot pump offers an alternative. We randomised 229 patients undergoing primary, unilateral TKR to receive either the A-V Impulse foot pump or enoxaparin, a LMWH. Ascending venography was undertaken between the sixth and eighth postoperative day in 188 patients without knowledge of the randomisation category. The prevalence of venographic deep-vein thrombosis was 58% (57/99) in the foot-pump group and 54% (48/89) in the LMWH group which was not statistically significant. There were four cases of proximal thrombi and two of fatal pulmonary emboli in the foot-pump group and none in the LMWH group. There were fewer haemorrhagic complications and soft-tissue effects in the foot-pump group. We conclude that the neither method provides superior prophylaxis.     

Spontaneous spinal subdural hematoma associated with low-molecular-weight heparin. Case report

Spinal subdural hematomas (SDHs) are a rare cause of cord compression and typically occur in the setting of spinal instrumentation or coagulopathy. The authors report the first case of a spontaneous spinal SDH occurring in conjunction with low-molecular-weight heparin use in a patient with a history of spinal radiotherapy.     

Comparison of low-molecular-weight heparin (enoxaparin sodium) and standard unfractionated heparin for haemodialysis anticoagulation.

BACKGROUND: Low-molecular-weight heparin (LMWH) has been suggested as providing safe, efficient, convenient and possibly more cost-effective anticoagulation for haemodialysis (HD) than unfractionated heparin, with fewer side-effects and possible benefits on uraemic dyslipidaemia. METHODS: In this prospective, randomized, cross-over study we compared the safety, clinical efficacy and cost effectiveness of Clexane (enoxaparin sodium; Rh?ne-Poulenc Rorer) with unfractionated heparin in 36 chronic HD patients. They were randomly assigned to either Clexane (1 mg/kg body weight, equivalent to 100 IU) or standard heparin, and followed prospectively for 12 weeks (36 dialyses) before crossing over to the alternate therapy for a further 12 weeks. Heparin anticoagulation was monitored using activated coagulation times. RESULTS: Dialysis with Clexane resulted in less frequent minor fibrin/clot formation in the dialyser and lines than with heparin (P<0.001), but was accompanied by increased frequency of minor haemorrhage between dialyses (P<0.001). Clexane dose reduction (to a mean of 0.69 mg/kg) eliminated excess minor haemorrhage without increasing clotting frequencies. Mean vascular compression times were similar in both groups. Over 24 weeks, no changes in standard serum lipid profiles were observed. CONCLUSIONS: This study suggests that a single-dose protocol of Clexane is an effective and very convenient alternative to sodium heparin, but currently direct costs are about 16% more. We recommend an initial dose of 0.70 mg/kg.     

Intraoperative heparin in addition to postoperative low-molecular-weight heparin for thromboprophylaxis in total knee replacement

The administration of heparin during operation has been reported to enhance the efficacy of thromboprophylaxis in patients undergoing total hip replacement. We have performed a small pilot study in which intraoperative doses of heparin were given in addition to the usual postoperative thromboprophylaxis with enoxaparin in 32 patients undergoing total knee replacement. The primary endpoint was deep-vein thrombosis (DVT) as demonstrated by bilateral venography on 6 +/- 2 days after operation. Sixteen patients developed DVT; in two the thrombosis was proximal as well as distal and in one the occurrence was bilateral. There was one major haemorrhage. These results are similar to those obtained with the use of postoperative thromboprophylaxis with enoxaparin alone. They do not provide support for the initiation of a larger randomised trial of this approach to management.     

The thromboprophylactic effect of a low-molecular-weight heparin (Fragmin) in hip fracture surgery. A placebo-controlled study.

A prospective, randomized, double-blind trial concerning thromboprophylaxis in 82 patients in whom hip fracture surgery was performed was conducted to compare a new low-molecular-weight heparin (Fragmin) with placebo. Deep venous thrombosis (DVT) was detected by 125-I-fibrinogen uptake test followed by ascending phlebography when positive. Sixty-eight patients completed the study, and a 50% reduction in the incidence of DVT was demonstrated: nine of 30 patients in the treatment group (30%) and 22 of 38 patients in the placebo group (58%) developed DVT. This significant difference was achieved by one daily dose of 5000 IU Fragmin subcutaneously, commenced preoperatively and continued for six days. There were no differences in bleeding or other complications in the two groups. Fragmin given once daily offers an effective and safe thromboprophylaxis in hip fracture surgery.