Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis. Low molecular weight heparin (Alfa LHWH) compared with unfractionated heparin in prevention of deep-vein thrombosis after hip fractures. Can low molecular weight heparin replace unfractionated heparin during peripheral arterial reconstruction? An open label prospective randomized controlled trial. Long-term treatment of deep venous thrombosis with a low molecular weight heparin (tinzaparin): a prospective randomized trial. Controlled clinical study of the efficacy of a new low molecular weight heparin administered subcutaneously to prevent post-operative deep venous thrombosis. Low-molecular-weight heparin versus unfractionated heparin in the treatment of patients with acute pulmonary thromboembolism. [Prevention of thromboembolism with low molecular weight heparin (Fragmin) in obstetrics]. Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial. High versus low doses of unfractionated heparin for the treatment of superficial thrombophlebitis of the leg. A prospective, controlled, randomized study. A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis.
The primary objective of this study was to evaluate with venography the rate of thrombus regression after a fixed dose of low-molecular weight heparin (LMWH) per day for 3 months compared with oral anticoagulant therapy for deep venous thrombosis (DVT). Secondary endpoints were the comparisons of the efficacy and safety of both treatments.
                This study was designed as an open randomized clinical study in a university hospital setting. Of the 165 patients finally enrolled in the study, 85 were assigned LMWH therapy and 80 were assigned oral anticoagulant therapy. In the group randomized to oral anticoagulant therapy, the patients first underwent treatment in the hospital with standard unfractionated heparin and then coumarin for 3 months. Doses were adjusted with laboratory monitoring to maintain the international normalized ratio between 2.0 and 3.0. Patients in the LMWH group were administered subcutaneous injections of fixed doses of 40 mg enoxaparin (4000 anti-Xa units) every 12 hours for 7 days, and after discharge from the hospital, they were administered 40 mg enoxaparin once daily at fixed doses for 3 months without a laboratory control assay. A quantitative venographic score (Marder score) was used to assess the extent of the venous thrombosis, with 0 points indicating no DVT and 40 points indicating total occlusion of all deep veins. The rate of thrombus reduction was defined as the difference in quantitative venographic scores after termination of LMWH or coumarin therapy as compared with the scores obtained on the initial venographic results. The efficacy was defined as the ability to prevent symptomatic extension or recurrence of venous thromboembolism (documented with venograms or serial lung scans). The safety was defined as the occurrence of hemorrhages.
                After 3 months of treatment, the mean Marder score was significantly decreased in both groups in comparison with the baseline score, although the effect of therapy was significantly better after LMWH therapy (49.4% reduction) than after coumarin therapy (24.5% reduction; P <.001). LMWH therapy and male gender were independently associated with an enhanced resolution of the thrombus. A lower frequency of symptomatic recurrent venous thromboembolism was also shown in patients who underwent treatment with LMWH therapy (9.5%) than with oral anticoagulant therapy (23.7%; P <.05), although this difference was entirely a result of recurrence of DVT. Bleeding complications were significantly fewer in the LMWH group than in the coumarin group (1. 1% vs 10%; P <.05). This difference was caused by minor hemorrhages. Coumarin therapy and cancer were independently associated with an enhanced risk of complications. Subcutaneous heparin therapy was well tolerated by all patients.
                The patients who were allocated to undergo enoxaparin therapy had a significantly greater improvement in their quantitative venographic score, a significantly lower recurrence rate of symptomatic venous thromboembolism, and a significantly lower incidence of bleeding than patients who underwent treatment with coumarin. LMWH can be used on an outpatient basis as a safer and more effective alternative to classical oral anticoagulant therapy for the secondary prophylaxis of selected patients with DVT. Efficacy and safety of a low molecular weight heparin (Alfa LMWH) was compared with unfractionated heparin (UFH) in the prevention of post-operative venous thromboembolism after hip fractures. Forty-nine patients were randomized to treatment with Alfa LMWH 7500 anti-Xa coagulometric units twice daily or with UFH 5000 IU t.i.d. Screening for thrombosis was performed with 125-I-fibrinogen leg scanning and strain-gauge plethysmography. Positive results were confirmed by venography. Five patients in the Alfa LMWH group (20 per cent) developed venographycally proven deep vein thrombosis (DVT) versus seven (29 per cent) in the UFH group. One pulmonary embolism and two deaths occurred in the UFH group and none in the LMWH group. No differences in haemorrhagic complications and blood loss indices were observed. Alfa LMWH appears to be a promising drug for prevention of venous thromboembolism after orthopaedic surgery. A "flexible" schedule of administration is proposed on the basis of the results of plasma anti-Xa assays. This study was undertaken to evaluate the effect of low molecular weight heparin (LMWH) compared with unfractionated heparin (UFH) on the rate of occlusion and bleeding during peripheral vascular surgery.
                The study was an open label, prospective, randomized trial, carried out by 20 Swedish surgical and vascular surgical departments that report to the Swedish Vascular Registry (SWEDVASC). Study subjects included patients undergoing peripheral vascular procedures, except carotid surgery. Of the 849 patients included, 817 were followed up to 30 days. LMWH (40 mg of enoxaparin) or UFH (5000 IU heparin) was given intravenously immediately before clamping. The same formulation in diluted form was used for vascular rinsing. Main outcome measures included patent reconstruction at day 1, perioperative blood loss, and the percentage of patients requiring protamin. Further, 30-day data for mortality, repeat operation, and recurrent occlusion are reported.
                The mortality rate at 30 days was 2.7%, with no difference between groups. The patency rate at 1 day was 91.2% to 98.4%, depending on diagnosis and type of reconstruction. No difference was recorded between study groups (0.6 < P < 1.0). At 30 days the patency rate was 83.1% to 100% (0.2 < P <.9). Median blood loss was 350 mL (interquartile range [IQR], 200-800 mL) in the LMWH group and 425 mL (IQR, 200-900 mL) in the UFH group (P =.02). Protamin was given to significantly fewer patients in the LMWH group (P =.001). LMWH was comparable to UFH during peripheral vascular reconstruction in terms of 1-day and 30-day graft patency, operative blood loss, and hemorrhagic complications. Protamine was required less often after LMWH. In this randomized trial LMWH was as effective as UFH in preventing thrombosis without excess bleeding or hemorrhagic complications. Evaluation of the effectiveness and safety of the low molecular weight heparin (LMWH) tinzaparin versus unfractionated heparin (UFH) followed by acenocoumarol in proximal deep venous thrombosis (DVT).
                Prospective, randomized clinical trial.
                Consecutive patients (n=108) with acute leg DVT, confirmed by duplex, were randomized to either tinzaparin alone or UFH and acenocoumarol for 6 months. Patients were evaluated ultrasonographically at entry, 1, 3, 6 and 12 months. Thrombus regression, reflux distribution and the incidence of complications were studied. A cost-analysis, comparing the two treatments, was performed.
                The overall incidence of major events (mortality, DVT recurrence, pulmonary embolism, major bleeding, heparin-induced thrombocytopenia) was significantly different (p=0.035) in favor of tinzaparin (7 versus 17 events). The ultrasonographic clot volume score (an index of recanalization) decreased significantly in both treatment groups. However, tinzaparin produced significantly more extended overall recanalization from 3 months onwards (p<0.02). Thrombus regression was equivalent or in favor of tinzaparin in the different DVT subgroups and venous segments, but the statistical significance varied. Reflux showed non-significant differences overall or in subgroups. A cost-analysis resulted in favor of LMWH.
                A fixed daily dose of tinzaparin for 6 months was at least as effective and safe as UFH and acenocoumarol. Regarding major events and recanalization, there was a significant benefit in favor of tinzaparin. Long-term DVT treatment with tinzaparin could represent an alternative to conventional treatment. A double-blind, placebo-controlled study was carried out in 100 patients undergoing major surgery to investigate the efficacy of a new low molecular weight heparin (LMWH) preparation in the prevention of deep venous thrombosis. Patients were allocated at random to receive either placebo or LMWH (7500 AXaU) each day by subcutaneous injection (abdominal fold method), starting 2 hours before the operation and continuing for the following 7 days. Clinical and laboratory tests revealed deep venous thrombosis in 3 (6%) patients in the placebo group whereas no thrombotic episodes were observed in any of the patients treated with LMWH. Blood loss during the peri-operative and post-operative period and the number of blood units transfused were not significantly different in the two groups. Moreover, no side-effects were revealed in the LMWH group that could be attributed to the drug. Low-molecular-weight heparin (LMWH) appears to be as effective as unfractionated heparin (UFH) for both treatment and prophylaxis of deep vein thrombosis (DVT), but limited data are available for its use in acute pulmonary thromboembolism (PTE).
                To determine whether enoxaparin, a LMWH, was clinically as efficient and safe as UFH in patients with a diagnosis of acute PTE.
                After exclusion of those with massive forms, 59 patients with acute PTE were randomly assigned to either subcutaneous enoxaparin given twice daily (1 mg/kg/dose) or adjusted dose intravenous UFH. Oral anticoagulant treatment was begun on the second day and was given for at least 6 months. We compared the treatment regimens at day 8 and day 90 with respect to a combined end point of major bleeding, recurrent venous thromboembolism (VTE), and death.
                In the first 8 days of treatment, 1 of 30 patients assigned to receive UFH (3.3%) reached one of the end points (recurrence), as compared with none of 29 patients assigned to enoxaparin. Statistically this difference was not significant (p = 0.508). By day 90, 3 patients assigned to UFH (10%) had symptomatic recurrent VTE, as compared with 1 patient assigned to enoxaparin (3.4%). There was neither major bleeding nor death in the study groups. There was an absolute difference of 6.4 percentage points between the two treatment groups, but the difference was statistically not significant (p = 0.318).
                Initial subcutaneous treatment with enoxaparin appeared to be as effective and safe as UFH in acute PTE.
                Copyright 2002 S. Karger AG, Basel A total of 130 obstetrical patients were treated with either low molecular weight (LMW) or unfractionated (UFH) heparin as part of prospective study comparing their efficacy in the prevention of thromboembolism. A single daily dose of 2500-5000 anti-Xa-units LMW heparin (Fragmin) or two to three daily doses of 5000 IU UFH (Liquemin) were given to two groups of 15 patients with therapeutic tocolysis and 50 patients with cesarean section. Patients with cesarean section were given 500 ml Dextran 60 i.v. during surgery followed by subcutaneous injection of heparin eight to ten hours after surgery. Heparin therapy was continued for ten days after surgery. None of the patients exhibited clinical signs of thrombosis. The majority of patients showed symptoms of local irritation at the site of heparin injection (69% of patients with LMW heparin; 80% of patients with UFH). Hematomas at the site of injection were significantly smaller when LMW heparin was used instead of UFH. A number of patients experienced headache after heparin application (10% of patients with LMW heparin; 13% of patients with UFH). There were no cases of post surgical haemorrhage. Comparison of daily profiles revealed a significantly higher anti-Xa-activity of LMW heparin compared to UFH. In contrast, other coagulation parameters were not different in the two experimental groups (antithrombin III, partial thrombin time, thrombin time). Hematologic parameters and liver enzymes were in the physiological range in both experimental groups and none of the patients exhibited signs of heparin induced thrombocytopenia.(ABSTRACT TRUNCATED AT 250 WORDS) Recent studies suggest that low molecular weight heparin (LMW heparin) therapy in malignancy may improve cancer survival following surgical resection. We studied prospectively whether cancer mortality during follow-up in women with previously untreated breast, and pelvic cancer is reduced in those who randomly received LMW heparin (Certoparin) compared to patients given unfractionated heparin (UF heparin) for thrombosis prophylaxis during primary surgery. In a prospective, randomized, double-blind clinical trial, 160 patients received Certoparin and 164 UF heparin until post-operatively day 7. Survival estimations are based on the outcome data from a subset of 140 LMW heparin - and 147 UF heparin recipients. Long-term survival in the Certoparin group compared to the UF heparin group was significantly improved after 650 days (P=0. 0066) but not thereafter when analysis was performed on all cancer cell types combined. In the probability estimates survival benefit within this time was restricted to patients with pelvic cancer but was not observed in breast cancer. However, in breast cancer patients who received LMW heparin the impact of classical tumor prognostic markers was statistically significant after 1,050 days but not after 650 days. Thus, breast cancer patients with unfavorable prognosis seem to benefit in terms of survival advantage from LMW heparin within the 650 days after surgery. These results suggest that improvement in cancer survival can be achieved after even a short course of treatment with LMWH (compared to UFH) given for DVT prophylaxis in the post-operative period. An effect of UFH on disease outcome is not excluded. Further definitive trials of LMWH vs. placebo for cancer outcome (rather then DVT) using doses and schedules that may be more optimal are indicated. The optimal treatment of superficial thrombophlebitis of the leg is undefined. The main study objective was to assess the efficacy and safety of unmonitored high doses as compared to low doses of unfractionated heparin (UFH) for prevention of venous thromboembolic complications in patients with superficial thrombophlebitis of the thigh.
                Sixty consecutive patients with acute thrombophlebitis of the great saphenous vein, as assessed by ultrasonography, were randomized to subcutaneous injection twice daily of UFH in high unmonitored doses (12,500 IU for one week followed by 10,000 IU) or prophylactic doses (5,000 IU) for four weeks. The rate of asymptomatic involvement of the deep venous system and/or symptomatic thromboembolic events during a six-month follow-up period was assessed and compared between the two study groups.
                Six of the 30 patients (20.0 %; 95% CI, 7.7 to 38.6) randomized to low-dose UFH developed symptomatic or asymptomatic events as compared to 1 of the 30 patients (3.3%; 95% CI, 0.07 to 17.2) who received high-dose UFH (p=0.05 by one-sided Fisher's exact test). No patient experienced major bleeding complications in either group.
                The results of this study suggest that in patients with acute thrombophlebitis of the thigh unmonitored high doses of UFH are more effective than prophylactic doses of UFH for prevention of venous thromboembolic complications and do not enhance the risk of bleeding complications. To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT).
                A randomised, open-label trial.
                In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months.
                During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group.
                Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer.
We found no difference between perioperative thromboprophylaxis with LMWH verus UFH in their effects on mortality and embolic outcomes in patients with cancer. Further trials are needed to more carefully evaluate the benefits and harms of different heparin thromboprophylaxis strategies in this population.