Prevention of deep vein thrombosis after hip replacement: randomised comparison between unfractionated heparin and low molecular weight heparin.

OBJECTIVE--To evaluate the efficacy and safety of two subcutaneous prophylactic regimens for postoperative deep vein thrombosis after total hip replacement. DESIGN--Prospective open randomised multicentre trial. SETTING--28 European departments of orthopaedic surgery. INTERVENTION--All patients had bilateral phlebography 10 days after surgery. 31 patients receiving low molecular weight heparin and 29 receiving unfractionated heparin were excluded from the efficacy analysis for various reasons. PATIENTS--349 patients undergoing total hip replacement between September 1988 and May 1989. 174 patients received subcutaneously a low molecular weight heparin (Fraxiparine) with anti-factor Xa activity of 41 IU/kg/day for three days, then 62 IU/kg/day from day 4 to day 10. 175 patients received subcutaneous unfractionated heparin at intervals of eight hours; doses were adjusted to maintain the activated thromboplastin time at two to five seconds above control values. MAIN OUTCOME MEASURE--Total incidence of deep vein thrombosis and incidence of proximal deep vein thrombosis on bilateral phlebography. RESULTS--The total incidence of deep vein thrombosis was 16% in patients receiving unfractionated heparin and 12.6% in patients receiving low molecular weight heparin (p = 0.45), and the incidence of thrombosis of the proximal veins was 13.1% and 2.9% respectively (p less than 0.001). Four patients receiving unfractionated heparin and one receiving low molecular weight heparin developed pulmonary embolism. The incidence of bleeding complications was low and comparable in the two groups. CONCLUSION--Low molecular weight heparin is at least as effective as unfractionated heparin in preventing deep vein thrombosis and is more effective at preventing thrombosis of the proximal veins in patients undergoing hip replacement. Low molecular weight heparin is not more likely to cause bleeding complications and is simpler to give than unfractionated heparin.     

Prevention of Postoperative Leg Vein Thrombosis by Electrical Muscle Stimulation. An Evaluation with 125I-Labelled Fibrinogen

In a prospective trial of preventing deep vein thrombosis electrical stimulation of the calf muscles of one leg was used in 110 patients undergoing major surgery. Deep vein thrombosis was detected by means of the ¹²⁵I-fibrinogen uptake test in nine of the stimulated legs and in 23 of the unstimulated legs. It is suggested that this technique, which is both simple and effective, should be used on all patients undergoing major surgery.     

Low-molecular-weight heparin and prevention of postoperative deep vein thrombosis.

The efficacy of low-molecular-weight heparin as a prophylactic agent was assessed in 150 consecutive patients over the age of 40 undergoing major abdominal surgery. Fifty of these patients received 1250 activated partial thromboplastin time (APTT) units of low-molecular-weight heparin every 12 hours: three developed isotopic deep vein thrombosis, which was confirmed by phlebography in two cases. The other 100 patients received a single injection of 1850 APTT units of low-molecular-weight heparin. Three of them developed isotopic deep vein thrombosis; phlebography failed to confirm the presence of thrombi in each case. None of the 150 patients studied died from fatal or contributory pulmonary emboli. Low-molecular-weight heparin was not associated with any increase in preoperative or postoperative bleeding. The effect of equal amounts of postoperative bleeding. The effect of equal amounts of low-molecular-weight heparin and unfractionated heparin on the coagulation mechanism during surgery was investigated in another 30 patients. The clotting assays and results of in-vivo platelet function tests indicated that both preparations produced similar effect. Intragroup comparisons, however, showed significant differences in the anti-factor Xa activity, lipoprotein lipase release, and plasma prekallikrein concentrations. A single injection of low-molecular-weight heparin daily is a convenient way of preventing deep vein thrombosis in high-risk patients undergoing major abdominal surgery.     

Preventing thromboembolism after myocardial infarction: effect of low-dose heparin or smoking.

A trial of low-dose subcutaneous heparin to prevent thromboembolic complications after myocardial infarction was carried out in 78 patients. Of the 37 heparin-treated patients only two (5%) developed evidence of leg vein thrombosis, while 14 (34%) of the 41 controls did so, and five controls developed pulmonary emboli. Leg vein thrombosis developed in 12 (50%) of the 24 controls who did not smoke cigarettes but in only two (13%) of the 17 controls who were cigarette smokers. Non-smokers who have a myocardial infarction should be given low-dose heparin subcutaneously to prevent leg vein thrombosis and pulmonary embolism.     

Treatment of deep vein thrombosis with streptokinase.

From September 1962 to May 1972 145 patients with acute or subacute deep vein thrombosis confirmed by phlebography were treated with streptokinase. During the same period 42 patients considered unfit for thrombolytic therapy were treated with herapin and oral anticoagulants. The results, assessed by repeat phlebography, in 93 of the patients treated with streptokinase were compared with those in 42 patients treated with heparin. The age, sex, and severity of occlusion were roughly similar in both groups. Streptokinase treatment was successful in 42 per cent, partially successful in 25 per cent, and unsuccessful in 32 per cent of the 93 patients compared with none, 10 per cent, and 88 percent respectively in the 42 patients treated with heparin. Streptokinase was more effective when the thrombus was in proximal rather than calf veins. Thrombi of more than six days old were readily lysed. Plasma fibrinogen levels were below 0-8 g/1 (80 mg/100 ml) in nearly all patients successfully treated. The incidence of pulmonary embolism was no greater with streptokinase than with heparin treatment. Only prolonged follow-up would show whether thrombolytic treatment would be effective in preventing late complications of deep vein thrombosis such as chronic venous insufficiency.     

Subcutaneous calcium heparin versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective randomised trial.

One hundred patients with phlebographically proved acute deep vein thrombosis of the legs were prospectively randomised into two treatment groups to compare the safety and efficacy of subcutaneous calcium heparin versus intravenous sodium heparin administered by constant infusion pump. The dose of heparin was determined by daily measurement of the kaolin cephalin clotting time. Treatment was maintained for up to 14 days, after which phlebography was repeated. Of 49 patients who received subcutaneous calcium heparin, two showed an increase in thrombus size, while eight showed complete lysis. In the 47 patients who received intravenous sodium heparin thrombus increased in size in 13 while only one showed evidence of complete lysis. These differences were significant. There were no significant differences between the two groups in the incidence of serious complications, although almost half of those receiving intravenous heparin had some minor problem with the constant infusion pump and just over half of those receiving subcutaneous heparin had some bruising at the injection site. This study showed that subcutaneous calcium heparin was more effective in helping lyse existing thrombus and preventing its propagation than intravenous sodium heparin.     

不同方案治疗直径小于10cm肝细胞癌合并门静脉癌栓患者影响生存率的观察

目的：探讨两种不同方案治疗直径小于10cm肝细胞癌合并门静脉癌栓患者影响生存率。方法：将我院100例直径小于10cm肝细胞癌合并门静脉癌栓患者按照抽签法随机地均分为A、B两组,A组行单纯肝动脉插管化疗栓撒（TACE）治疗,B组肝癌手术切除联合癌栓切除＋TACE术,比较两组患者治疗前后DLIA蛋白与VEGF蛋白阳性表达率、五年生存率以及影响患者生存率的因素。结果：（1）A组治疗前后DLL4蛋白与VEGF蛋白阳性表达率差异无统计学意义（P〉0．05）,B组治疗前后上述蛋白阳性表达率差异具有统计学意义（P〈0．05,P〈0．01）;（2）根据Kaplan—Meir计算方法,B组五年生存率均明显大于A组（P〈0．001）;（3）经Pearson单因素与COX多因素分析,影响患者预后的危险独立因素为肿瘤大小与手术方式。结论：综合治疗方案用于治疗直径小于10cm肝细胞癌合并门静脉癌栓患者之中,疗效显著,患者五年生存率明显提高。     

Low-dose heparin prophylaxis against fatal pulmonary embolism.

A prospective randomised controlled trial in 500 patients over the age of 50 who were undergoing major surgery showed that low-dose subcutaneous heparin was an effective prophylactic measure against fatal pulmonary embolism. None of the 252 patients who received perioperative heparin cover died of fatal pulmonary embolism while eight of the 236 who did not receive heparin prophylaxis died of fatal pulmonary embolism. These results were statiscally significant (P less than 0.01).     

Dextran 70 in Prophylaxis of Postoperative Venous Thrombosis. A Controlled Trial

A controlled prospective trial was carried out in a group of 80 women undergoing gynaecological surgery and thought to be at risk of developing postoperative venous thrombosis. The patients, who had been randomly allocated to prophylaxis with either dextran 70 or warfarin, were well matched in age, weight and other predisposing factors.In the warfarin group, 12 out of 40 patients developed deep vein thrombosis, six of these episodes being classified as major and six as minor. In the dextran 70 group, 4 out of 40 patients developed deep vein thrombosis, all of them minor. The protective effect of dextran 70 is significantly better than that of warfarin (P<0·01) as used in the present study.     

Postural Abnormality as a Risk Marker for Leg Deep Venous Thrombosis in Parkinson’s Disease

Background

Pulmonary thromboembolism is a common cause of death in patients with autopsy-confirmed Parkinsonism. This study investigated the incidence of leg deep vein thrombosis in Parkinson’s disease and relationships between deep vein thrombosis and clinical/laboratory findings, including postural abnormalities as assessed by photographic measurements.

Methods

This cross-sectional study assessed the presence of deep vein thrombosis using bilateral leg Doppler ultrasonography in 114 asymptomatic outpatients with Parkinson’s disease.

Results

Deep vein thrombosis was detected in 23 patients (20%) with Parkinson’s disease. Deep vein thrombosis was located in the distal portion in 18 patients and in the proximal portion in 5 patients. No significant differences in age, sex, body mass index, disease duration, Hoehn-Yahr stage, anti-Parkinson’s drugs, or daily levodopa-equivalent dose were seen between deep vein thrombosis-positive and -negative groups. Univariate analysis for developing deep vein thrombosis in patients with Parkinson’s disease identified the following markers: long-term wheelchair use, bent knee, bent spine, and D-dimer elevation. Bending angles were significantly greater in the deep vein thrombosis-positive group at the knee and spine than in the deep vein thrombosis-negative group. Half of Parkinson’s disease patients with camptocormia had deep vein thrombosis. Among diabetes mellitus cases, long-term wheelchair use, bent knee over 15°, camptocormia, D-dimer elevation, the more risk markers were associated with a higher incidence of DVT. The presence of risk markers contributed to the development of deep vein thrombosis. On multivariate logistic regression analysis, a bent knee posture was strongly associated with an increased risk of deep vein thrombosis.

Conclusion

Presence of leg deep vein thrombosis correlated with postural abnormalities in Parkinson’s disease. We recommend non-invasive ultrasonographic screening for leg deep vein thrombosis in these high-risk patients with Parkinson’s disease.     

Subcutaneous injections and intravenous infusion of sodium salt of heparin in the treatment of thrombosis of deep veins of the lower extremities

Ninety-four patients with deep vein thrombosis of inferior limbs were randomly allocated to receive sodium heparin either by subcutaneous injections or by continuous intravenous infusion for six days. No significant difference was observed in the therapeutic efficiency as judged by phlebographic examinations and in rate of symptomatic pulmonary embolism between the two groups. There was one instance of major bleeding in the subcutaneous group. Minor bleedings occurred in 10 of the 48 patients treated with subcutaneous heparin and in 13 of the 46 patients receiving intravenous heparin. The results showed that subcutaneous injections of sodium heparin are as effective and safe as continuous intravenous infusion of this drug in the treatment of deep vein thrombosis.     

Effect of Externally Applied Pressure on Femoral Vein Blood Flow

The effect of incremental increases in external pressure, applied to the leg, on blood volume flow in the femoral vein was studied in dogs. Clinical investigation of external pressure increases was also carried out on nine patients undergoing surgery for varicose veins. An external pressure between 5 and 15 mm. Hg caused a sustained increase in mean femoral vein flow both in a control and in the compressed limb. Above 15 mm. Hg external pressure flow decreased in the compressed limb but was maintained at an increased level in the control limb.If external compression is to be used to prevent and treat deep vein thrombosis its application must be carefully controlled.     

Collaborative overview of randomised trials of antiplatelet therapy--III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists' Collaboration.

OBJECTIVE--To determine the efficacy of antiplatelet therapy as prophylaxis against deep venous thrombosis or pulmonary embolism in surgical and high risk medical patients. DESIGN--Overviews of all randomised trials of antiplatelet therapy that could have been available by March 1990 and in which deep venous thrombosis was assessed systematically. SETTING--53 trials (total 8400 patients) of an average of two weeks of antiplatelet therapy versus control in general or orthopaedic surgery; nine trials (600 patients) of antiplatelet therapy versus control in other types of immobility; 18 trials (1000 patients) of one antiplatelet regimen versus another. RESULTS--Overall, a few weeks of antiplatelet therapy produced a highly significant (2P < 0.00001) reduction in deep venous thrombosis. 25% of patients allocated antiplatelet therapy versus 34% of appropriately adjusted controls had deep venous thrombosis detected by systematic fibrinogen scanning or venography, representing prevention in about 90 patients per 1000 allocated antiplatelet therapy. There was an even greater proportional reduction in pulmonary embolism: such emboli were detected among 47 (1.0%) antiplatelet allocated patients versus an adjusted control total of 129 (2.7%), representing prevention among about 17 patients per 1000 treated (2P < 0.00001). In analyses confined to surgical trials, the proportional reductions were similar and separately significant for nonfatal pulmonary embolism (0.7% antiplatelet therapy v 1.8% control; 2P < 0.00001) and for deaths attributed to pulmonary embolism (0.2% v 0.9%; 2P = 0.0001). There was a slight but non-significant excess of deaths from other causes (1.0% v 0.7%), which made the difference in total mortality nonsignificant, though still favourable (1.2% v 1.5%). Information on adding antiplatelet therapy to heparin was limited but, at least for pulmonary embolism, suggested more protection from the combination than from heparin alone. The proportional reduction in the odds of suffering a deep venous thrombosis was roughly the same in patients having general surgery, traumatic orthopaedic surgery, and elective orthopaedic surgery (and in medical patients who were at increased risk of thromboembolism). For pulmonary embolism the numbers affected were smaller, but again the reductions were highly significant both in general surgery (16 (0.5%) v 58 (1.7%) pulmonary emboli; 2P < 0.0001) and in orthopaedic surgery (28 (2.7%) v 63 (6.1%) pulmonary emboli; 2P < 0.0002). CONCLUSION--It had previously been supposed that antiplatelet therapy did not influence venous thromboembolism, and many surgeons and physicians do not use it routinely for thromboprophylaxis, even for patients who are at substantial risk of deep venous thrombosis or pulmonary embolism. These results indicate that antiplatelet therapy--either alone or, for greater effect, in addition to other proved forms of thromboprophylaxis (such as subcutaneous heparin)--should be considered.     

Prevention of Early Postoperative Deep Vein Thrombosis by Passive Exercise of Leg during Surgery

A clinical trial assessed the effect of passive exercise of the lower limb during surgery on the incidence of early postoperative deep vein thrombosis. Thrombosis was diagnosed by means of the ¹²⁵I-fibrinogen uptake test. Passive exercise of the lower limb during the operation was achieved by using a motorized foot mover designed for use on supine subjects, and by pedalling only one leg each patient acted as his own control.In a sequential statistical analysis, 47 patients were required to reach the 5% level of significance. Thrombosis was detected in 11 control (unpedalled) legs alone, and in only one pedalled leg alone. Two patients developed thrombosis bilaterally. The investigation shows that the incidence of early thrombosis in legs which were exercised during surgery was reduced by 77%.     

Passive Flexion and Femoral Vein Flow: A Study Using a Motorized Foot Mover

The effect of rhythmic passive flexion of the foot on femoral vein blood volume flow rate has been investigated in 11 patients undergoing surgery for varicose veins. With rates of flexion varying from 24 to 50 per minute and with amplitudes varying from 20° to 50° it has been shown that the peak femoral vein flow can be increased to twice its normal value and that its pulsatility can be increased elevenfold. These increases are proportional to both the rate and the amplitude of the flexion, the maximum occurring, theoretically, when the foot is flexed ±28° about a line perpendicular to the leg.The investigation has further shown that the effects of sustained passive flexion are maintained, without appreciable dimunition, for 30 minutes and that the maximum increases are produced in those patients who have the lowest resting flows. It is suggested that per-operative passive flexion of the feet may be a good prophylactic against postoperative deep vein thrombosis.     

香豆乙酯与华法林预防髋膝关节手术后下肢深静脉血栓形成的效果比较

目的:比较香豆乙酯与华法林预防髋膝关节手术后下肢深静脉血栓形成的疗效。方法:选取我院行髋膝关节手术患者38例,随机分为实验组和对照组,每组19例。对照组给予低分子量肝素及香豆乙酯片治疗;实验组给予低分子量肝素及华法林治疗。观察并比较两组患者的临床效果、下肢深静脉血栓的发生率及不良反应的发生情况。结果:实验组总有效率(94.7%)高于对照组(68.4%),差异有统计学意义(P0.05);实验组患者下肢深静脉血栓发生率(5.3%)低于对照组(21.1%),差异有统计学意义(P0.05);实验组不良反应发生率(15.8%)低于对照组(42.1%),差异有统计学意义(P0.05)。结论:与双香豆乙酯相比,华法林预防髋膝关节手术患者下肢深静脉血栓形成的效果更显著,且并发症较少。     

Assessment of Novel Anti-thrombotic Fusion Proteins for Inhibition of Stenosis in a Porcine Model of Arteriovenous Graft

Background

Hemodialysis arteriovenous synthetic grafts (AVG) provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study’s objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis.

Methods

A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries.

Results

No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft thrombosis as intravenous administration of heparin, but failed to inhibit hyperplasia development and stenosis in AVG.     

Prevention of Early Postoperative Deep Vein Thrombosis by Intermittent Compression of the Leg during Surgery

A clinical trial is described in which the effect of intermittent compression of the lower limb during surgery on the incidence of early postoperative deep vein thrombosis was assessed. Deep vein thromboses were diagnosed by the ¹²⁵I-fibrinogen uptake test. Peroperative intermittent compression was achieved by means of an inflatable plastic splint coupled to a pneumatic controller. By compressing only one leg of each patient, each patient acted as his own control.With a sequential statistical analysis, 39 patients were required to pass the 5% level of significance. Eleven thrombi were detected in the control (uncompressed) legs and two occurred in the compressed legs; one of the latter was bilateral. The investigation shows that increasing the pulsatility of the venous flow in the leg is a potent prophylactic against postoperative deep vein thrombosis.     

低分子肝素钙联合银杏达莫注射液应用于股骨粗隆间骨折术后下肢深静脉血栓形成的疗效观察

目的:探讨低分子肝素钙联合银杏达莫注射液应用于股骨粗隆间骨折术后下肢深静脉血栓形成的治疗效果。方法:选择2015年6月至2016年12月间我院骨科收治的股骨粗隆间骨折的患者80例,按随机数字表法分为研究组和对照组,每组各40例。两组患者均接受手术治疗,对照组术后应用低分子肝素钙6000IU治疗,皮下注射,2次/d;研究组在此基础上应用银杏达莫注射液20 m L治疗,静脉滴注,1次/d,疗程均为10 d。观察两组患者术后下肢深静脉血栓发生率、髌骨上极上15 cm周径、髌骨下极下15 cm周径及肿胀率,治疗前后凝血酶原时间(PT)、活化部分凝血活酶时间(APPT)、D-2聚体(D-D)水平和血液流变学检查指标。结果:治疗期间研究组下肢深静脉血栓发生率为2.50%,显著低于对照组的15.00%(P0.05)。治疗后两组患者髌骨上极上15cm周径、髌骨下极下15 cm周径均轻微增高,与治疗前比较无统计学差异(P0.05)。两组患者髌骨上极上15 cm肿胀率、髌骨下极下15 cm肿胀率比较无统计学差异(P0.05)。治疗后2d研究组患者PT、APPT显著高于对照组,D-D显著低于对照组(P0.05),治疗后10 d研究组PT、APPT显著高于对照组,D-D显著低于对照组(P0.05)。治疗后2 d、治疗后10 d研究组全血低切、全血高切、血浆黏度、红细胞压积、红细胞聚集指数和纤维蛋白原显著低于对照组(P0.05)。结论:低分子肝素钙联合银杏达莫注射液可以降低血液凝固性,改善血液流变学,对预防股骨粗隆间骨折下肢深静脉血栓形成有良好的疗效。     

The effect of low-molecular-weight heparin in the survival of a rabbit congested skin flap

Swelling and congestion of flaps are frequently seen postoperatively and can cause unexpected necrosis. According to previous reports, venous thrombosis seems to be a more frequent problem than arterial occlusion in both experimental and clinical surgery. Few satisfactory venous trauma models exist, and reports on experimental venous thrombosis are rare. The object of this study was to create a rabbit venous occlusion flap model and to evaluate the effect of low-molecular-weight heparin on this flap. Eight New Zealand rabbits were used in the pilot study, in which the ideal congested flap was investigated using a flap pedicle based on the central auricular artery with a skin pedicle 0, 1, 2, or 3 cm wide. The flap (3 x 6 cm) was designed on the central part of the left ear, and the central auricular vein and nerve, the former for venous return, were cut out at the base of the flap. The flaps with skin pedicles 0, 1, 2, or 3 cm wide showed mean necrosis length of 60.0, 9.3, 4.2, and 0.0 mm, respectively. The flaps with skin pedicles 0, 1, 2, or 3 cm wide showed mean necrosis of 100, 15.5, 7, and 0 percent, respectively. Therefore, the flap, based on a 1-cm-wide skin pedicle and the central auricular artery, was selected as an optimal congested flap model showing 15.5 percent necrosis. The congested flap was then elevated on the left ear of another 10 rabbits. Subcutaneous low-molecular-weight heparin (320 IU/kg) was administered immediately after surgery to five of the rabbits (the low-molecular-weight heparin group), and the remaining five were used as a control group. Fluorescein was injected 15 minutes after surgery to evaluate the circulatory territory of the flap, and the circulatory territory was measured 5 minutes after injection. The flaps were assessed 7 days after surgery by angiography, histology, and clinical findings. The circulatory territory was significantly greater in the low-molecular-weight heparin group (mean +/- SD, 39.2 +/- 3.0 mm) than the control group (mean +/- SD, 48.0 +/- 1.0 mm) (p < 0.001) assessed 7 days after surgery. The longest flap survival length in group A and group B ranged from 40 to 55 mm (mean +/- SD. 49.4 +/- 5.6 mm) and complete survival (mean +/- SD, 60.0 +/- 0.0 mm). The improvement in survival was statistically significant for group B compared with group A (p < 0.015). Histologic evaluation revealed moderate to severe venous congestion and inflammation in the control group, whereas there were minimal changes in the low-molecular-weight heparin group. Angiography of the flap revealed obvious venous occlusion in the periphery in the control group compared with the low-molecular-weight heparin group. The authors conclude that subcutaneous administration of low-molecular-weight heparin has a great potential to improve the survival length of a congested flap without major complications.