A Fixed-Dose Combination of Low Molecular Weight Heparin with Dihydroergotamine versus Adjusted-Dose Unfractionated Heparin in the Prevention of Deep-Vein Thrombosis after Total Hip Replacement

1996 ◽  
Vol 75 (02) ◽  
pp. 246-250 ◽  
Author(s):  
T Horbach ◽  
H Wolf ◽  
H C Michaells ◽  
W Wagner ◽  
A Hoffmann ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Unfractionated Heparin ◽  
Hip Replacement ◽  
Fixed Dose ◽  
Once Daily ◽  
Vein Thrombosis ◽  
Risk Patients ◽  
Dose Combination ◽  
Deep Vein ◽  
Adjusted Dose

SummaryThe low dose heparin regimen (LDH) is not appropriate for prevention of intra- and postoperative thromboembolic complications in high risk patients, especially those undergoing elective hip replacement. Despite LDH prophylaxis, the incidence of deep-vein thrombosis (DVT) remains in a range of 20 to 35%. Adjusted-dose unfractionated heparin prophylaxis is thought to be one of the most effective regimens for thrombosis prophylaxis in this indication, but it requires two or three daily injections as well as precise monitoring of the activated partial thromboplastin time (aPTT). As an attractive alternative, we investigated the efficacy and safety of the low molecular weight heparin (LMWH) certoparin combined with dihydroergotamine (DHE) given once daily.In a randomised, open clinical trial, a total number of 305 patients undergoing total elective hip replacement were enrolled and divided into two groups, either receiving a fixed-dose combination of LMWH (3,000 IU) and DHE (0.5 mg) subcutaneously once daily, or adjusted-dose unfractionated heparin (UFH) subcutaneously every 8 h. The UFH dosage was adjusted daily to keep an aPTT of about 50 s. The aPTT was determined 3 h after the morning injection. During the study, the starting dose (15,000 IU/day) was increased to a plateau value of 28,800 ± 7,150 IU/day (mean ± SD) to maintain the aPTT in the prescribed range. The plateau value was achieved after 8 postoperative days. For analysis of efficacy 289 patients were evaluable. The occurrence of deep vein thrombosis was determined by bilateral ascending venography, which was performed on the same day in patients with clinical signs suggesting DVT; and in all remaining patients at the end of the prophylaxis period. Deep vein thrombosis was diagnosed in 17 of 142 patients (12.0%) treated with LMWH/DHE and in 13 of 147 patients (8.8%) treated with adjusted-dose UFH. Combined distal-proximal thrombosis was more frequently in patients receiving UFH (n = 5; 3.4%) compared to the LMWH/DHE group (n = 2; 1.4%). These differences are statistically not significant. In the UFH group one case of non-fatal pulmonary embolism occurred. Both prophylaxis regimens were well tolerated; wound bleeding was observed in 8 (5.3%) patients in the LMWH group and in 6 (4.0%) patients in the UFH group. Intraoperative blood-loss volume (mean±SD) was 751 ± 339 ml (LMWH/DHE) and 736 ± 380 ml (UFH), whereas postoperative drain-loss volume (mean ± SD) was found to be 523 ± 333 ml (LMWH/DHE) and 581 ± 404 ml (UFH). Whole blood transfusion volumes (mean ± SD) were 570 ± 202 ml (LMWH/DHE) and 748 ± 455 ml (UFH). Additionally, red cell replacement volumes (mean ± SD) were 804 ± 435 ml (LMWH/DHE) and 720 ± 328 ml (UHF). Revision of wound or additional drainage were necessary in 3 LMWH/DHE and 7 UFH patients. One patient needed reoperation due to bleeding, 3 (2.0%) had petechia and 1 exhibited an allergic exanthema, all of them in the UFH group. A slight erythema at the injection site was observed in 6 (3.9%) patients receiving LMWH/DHE. During the course of prophylaxis, injection hematomas were documented in 57.9% (LMWH/DHE) and in 61.4% (UFH) of the patients. All differences were statistically not significant.Single daily subcutaneous injections of LMWH/DHE appeared to be safe and efficacious compared to adjusted-dose UFH for prophylaxis of DVT in high-risk patients.

Comparison of Once-Daily Subcutaneous Fragmin® with Continuous Intravenous Unfractionated Heparin in the Treatment of Deep Vein Thrombosis

1994 ◽  
Vol 72 (02) ◽  
pp. 186-190 ◽  
Author(s):  
Per Lindmarker ◽  
Margareta Holmström ◽  
Staffan Granqvist ◽  
Hans Johnsson ◽  
Dieter Lockner
Keyword(s):  
Deep Vein Thrombosis ◽  
Unfractionated Heparin ◽  
Fixed Dose ◽  
Bleeding Events ◽  
Once Daily ◽  
Vein Thrombosis ◽  
Symptomatic Pulmonary Embolism ◽  
Venous Thromboembolic Events ◽  
Deep Vein ◽  
Change In Mean

SummaryTwo hundred and four consecutive patients with venographically confirmed deep vein thrombosis (DVT) were randomised either to a low molecular weight heparin, Fragmin®, administered subcutaneously (s.c.) once daily as a fixed dose of 200IU anti-factor Xa/kg or to continuous intravenous infusion of unfractionated heparin (UFH). The UFH dose was adjusted to maintain the activated partial thromboplastin time between 1.5 and 3.0 times the upper limit of the reference value at each centre. Fragmin® or UFH was given for a minimum of 5 days until anticoagulation with warfarin, given from day 1, was established (i. e. an International Normalised Ratio, of 2.0−3.0). A second venogram was obtained after Fragmin® or UFH treatment. There were no significant differences in the change in mean Marder score before and after treatment between the two treatment groups, irrespective of thrombus localisation. No major bleeding events, symptomatic pulmonary embolism, symptomatic thrombosis progression or death occurred during hospitalisation. Eight documented venous thromboembolic events occurred before the follow-up visit 6 months after randomisation: 5 in patients treated with Fragmin® and 3 in those treated with UFH. Six of these events occurred after cessation of warfarin treatment. In conclusion Fragmin® given s.c. once daily in a fixed dose adjusted for body weight, is no less effective or safe than a continuous infusion of UFH in the initial treatment of acute DVT.

Prevention of Postoperative Venous Thrombosis: A Randomized Trial Comparing Unfractionated Heparin with Low Molecular Weight Heparin in Patients Undergoing Total Hip Replacement

1988 ◽  
Vol 60 (03) ◽  
pp. 407-410 ◽  
Author(s):  
Andrè Planes ◽  
Nicole Vochelle ◽  
Frçngois Mazas ◽  
Christian Mansat ◽  
Jean Zucman ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Unfractionated Heparin ◽  
Randomized Trial ◽  
Hip Replacement ◽  
Heparin Group ◽  
Once Daily ◽  
Vein Thrombosis ◽  
Enoxaparin Group ◽  
Calcium Heparin ◽  
Deep Vein

SummaryA double blind randomized trial comparing subcutaneous enoxaparin (40 mg once daily) with standard unfractionated calcium heparin administered at a dose of 5,000 units every 8 hours in patients undergoing elective hip replacement has been performed. Treatment regimens began 12 hours preoperatively with enoxaparin, 2 hours preoperatively with standard unfractionated calcium heparin, and were continued for 15 days or until discharge. Venography was performed in all patients. Two hundred thirty-seven patients were included in the study: 113 received unfractionated heparin and 124 received enoxaparin. The incidence of proximal deep vein thrombosis was reduced from 18.5% in the unfractionated heparin group to 7.5% in the enoxaparin group (p = 0.014), and the incidence of total deep vein thrombosis was similarly reduced from 25% to 12.5% (p = 0.03). There were two major bleeding episodes and one minor bleed in the enoxaparin group compared to two minor bleeds in the unfractionated heparin group. Patients who received enoxaparin required fewer red blood cell transfusions and had a significantly higher hemoglobin on postoperative days 3 and 4. Thus prophylaxis with enoxaparin, 40 mg once daily, is simple, safe and more effective than standard low dose unfractionated heparin in preventing deep vein thrombosis in patients undergoing elective hip replacement.

Should Patients with Deep Vein Thrombosis Alone be Treated as Those with Concomitant Asymptomatic Pulmonary Embolism? A Prospective Study

2002 ◽  
Vol 88 (12) ◽  
pp. 938-942 ◽  
Author(s):  
Harry Büller ◽  
Anthonie Lensing ◽  
Montserrat Bonet ◽  
Javier Roncales ◽  
Jordi Muchart ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Major Bleeding ◽  
Odds Ratio ◽  
Vitamin K Antagonists ◽  
Fixed Dose ◽  
Once Daily ◽  
Bleeding Rate ◽  
Vein Thrombosis ◽  
Deep Vein

SummaryThe established initial treatment of patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) consists of the administration of subcutaneous, weight adjusted, low-molecular weight heparin (LMWH). However, the use of the same LMWH dosages for patients with either DVT or PE is not supported by data from comparative studies.1,000 consecutive patients with acute, proximal DVT were prospectively evaluated. All patients underwent a ventilation-perfusion lung scan on admission, and remained in hospital for at least 7 days. Patients with silent PE received once daily 10,000 to 15,000 IU subcutaneous LMWH dalteparin according to body weight for 7 days, and then vitamin K antagonists. Patients with DVT alone received LMWH in a fixed dose of 10,000 IU once daily for at least 5 days, and then vitamin K antagonists. The rate of both, major bleeding and symptomatic PE episodes during the 7-day study period was evaluated.Thirteen patients (1.3%) developed recurrent PE (1 died) and 16 patients (1.6%) had major bleeding (7 died). Recurrent PE was significantly more common in patients with silent PE (9 of 258 patients, 3.5%) than in those with DVT alone (4 of 742 patients, 0.5%. Odds ratio: 6.5; p <0.001). There were no significant differences in bleeding rate between patients with silent PE and those with DVT alone. However, the use of a fixed 10,000 IU dose in patients with DVT alone led to a significantly lower bleeding rate in patients weighing over 70 kg: 1 of 349 patients (0.3%) as compared to 9 of 393 patients (2.3%) in those weighing less than 70 kg (odds ratio: 0.12; p = 0.018).Fixed-dose 10,000 IU of LMWH dalteparin once daily proved to be both effective and safe in patients with DVT alone. The observed recurrence rate of 0.5% in these patients compares favourably with the 3.5% rate in patients with silent PE. Furthermore, this fixed-dosage was also safe. Patients weighing over 70 kg had a significant decrease in the rate of major bleeding, and no compensatory increase in the rate of recurrent PE.

Subcutaneous Low Molecular Weight Heparin versus Subcutaneous Unfractionated Heparin in the Treatment of Deep Vein Thrombosis: a Polish Multicenter Trial

1992 ◽  
Vol 68 (01) ◽  
pp. 014-018 ◽  
Author(s):  
S Lopaciuk ◽  
A J Meissner ◽  
S Filipecki ◽  
K Zawilska ◽  
J Sowier ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Deep Vein Thrombosis ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Multicenter Trial ◽  
Fixed Dose ◽  
Low Molecular Weight ◽  
Vein Thrombosis ◽  
The Difference ◽  
Deep Vein

SummaryIn a prospective multicenter trial, 149 consecutive patients with phlebographically proven proximal and/or distal deep vein thrombosis of the leg were randomly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 (Fraxiparine) in a fixed dose or unfractionated heparin (UFH) in doses adjusted according to the activated partial thromboplastin time. Pre- and post-treatment phlebograms were assessed blindly using the Arnesen’s score system in 134 patients available for analysis of the treatment efficacy. The mean phlebographic score after 10 days of treatment was significantly decreased in both groups (p <0.001) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant. There was an improvement in 45/ 68 patients (66%) in the Fraxiparine group and in 32/66 patients (48%) in the UFH group, and an increase in the thrombus size in 10/68 (15%) and 12/66 (18%), respectively. One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group. During a follow-up period of 3 months, two rethromboses had occurred in the UFH group and none in the Fraxiparine group. It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis.

Adjusted versus Fixed-Dose Subcutaneous Heparin in the Prevention of Deep-Vein Thrombosis after Total Hip Replacement

1983 ◽  
Vol 309 (16) ◽  
pp. 954-958 ◽  
Author(s):  
Pierre F. Leyvraz ◽  
Jacques Richard ◽  
Fedor Bachmann ◽  
Guy van Melle ◽  
Jean-Michel Treyvaud ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Total Hip Replacement ◽  
Hip Replacement ◽  
Fixed Dose ◽  
Total Hip ◽  
Vein Thrombosis ◽  
Subcutaneous Heparin ◽  
Deep Vein

Hemostatic Activation under Anticoagulant Treatment: A Comparison of Unfractionated Heparin vs. Nadroparin in the Treatment of Proximal Deep Vein Thrombosis

1999 ◽  
Vol 82 (10) ◽  
pp. 1227-1231 ◽  
Author(s):  
O. Marchetti ◽  
A. Haeberli ◽  
G. Mombelli ◽  
H. Stricker
Keyword(s):  
Deep Vein Thrombosis ◽  
Unfractionated Heparin ◽  
Time Course ◽  
Proximal Deep Vein Thrombosis ◽  
Once Daily ◽  
Vein Thrombosis ◽  
Hemostatic System ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
Deep Vein

Summary Background: Multiple clinical trials have been performed to compare standard heparin with low molecular weight heparin in the therapy of deep vein thrombosis, but little is known about the time course of the markers of hemostatic system during the treatment with these two heparin regimens. Methods: Twenty patients with proximal deep vein thrombosis confirmed by duplex ultrasound and phlebography were randomly assigned to either unfractionated heparin (UH) given as an intravenous bolus of 80 U/kg followed by a constant infusion of 18 U/kg/h, or nadroparin 185 AXa IU/kg once daily subcutaneously. Oral anticoagulants were started at day 4. Markers of hemostatic activation (F1+2, FPA, TAT, D-dimer) were measured daily for 4 days. Primary end-points were the time course of these markers; secondary endpoints consisted in the evaluation of thromboembolic and hemorrhagic complications by clinical outcome and Marder score. Results: Treatment with UH resulted in a rapid achievement of therapeutic heparin levels. UH reduced markers of fibrin formation and fibrinolysis more rapidly than nadroparin (p < 0.05). Within the nadroparin group activation of prothrombotic markers four hours after the subcutanous injection (peak level) was significantly lower when compared with the time prior to injection (trough level). Secondary endpoints showed no significant difference between the two groups. Conclusion: Continuous intravenous perfusion of UH administered on a basis of a weight-adjusted nomogram controlled markers of the hemostatic system more rapidly than once-daily subcutaneously administered weight-adjusted nadroparin.

Differential Inhibition of Thrombin Activity and Thrombin Generation by a Synthetic Direct Thrombin Inhibitor (Napsagatran, Ro 46-6240) and Unfractionated Heparin in Patients with Deep Vein Thrombosis

1999 ◽  
Vol 81 (04) ◽  
pp. 498-501 ◽  
Author(s):  
Henri Bounameaux ◽  
Herbert Ehringer ◽  
Alain Gast ◽  
Johan Hulting ◽  
Herbert Rasche ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Unfractionated Heparin ◽  
Thrombin Generation ◽  
Thrombin Inhibitors ◽  
Fixed Dose ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
Thrombin Activity ◽  
Deep Vein

Summary Background: Direct thrombin inhibitors belong to a new class of antithrombotic drugs whose effects on blood coagulation in vivo in patients suffering from acute thrombotic conditions have not yet been fully explored. Methods and Results: One hundred and five patients with acute proximal deep-vein thrombosis were randomized to receive a continuous intravenous infusion of napsagatran, a novel synthetic thrombin inhibitor, at a fixed dose of 5 mg/h (n = 36) or 9 mg/h (n = 25) for five days, or APTT-adjusted unfractionated heparin (UFH, n = 44) for the same time. In these patients, thrombin activity and thrombin generation could be assessed by measuring thrombin-antithrombin III complexes (TAT) and prothrombin fragment 1+2 (F1+2), respectively, on three occasions. At baseline, TAT and F1+2 did not differ among the three groups. On Day 2 (steady state), TAT significantly decreased in all groups, and the decrease was significantly more pronounced in the patients given higher-dose napsagatran. F1+2 decreased significantly only in UFH-treated patients. Two hours after cessation of the infusion, the TAT levels increased in the two napsagatran groups but not in the UFH group, whilst F1+2 went back to the baseline levels in the napsagatran-treated patients but remained low in the UFH-treated patients. There was no rebound effect. Conclusions: The data presented suggest that direct thrombin inhibition with napsagatran at 9 mg/h is more potent than UFH in attenuating thrombin activity, but is less potent than UFH in inhibiting thrombin generation. The real significance of these findings will have to be substantiated in further trials with clinically relevant endpoints.

Prevention of Deep-Vein Thrombosis following Total Hip Replacement Surgery with Enoxaparin versus Unfractionated Heparin: A Pharmacoeconomic Evaluation

1994 ◽  
Vol 28 (2) ◽  
pp. 271-275 ◽  
Author(s):  
Joseph Menzin ◽  
Randel Richner ◽  
Daniel Huse ◽  
Graham A. Colditz ◽  
Gerry Oster
Keyword(s):  
Deep Vein Thrombosis ◽  
Length Of Stay ◽  
Unfractionated Heparin ◽  
Total Hip Replacement ◽  
Hip Replacement ◽  
Total Hip ◽  
Replacement Surgery ◽  
Vein Thrombosis ◽  
Hip Replacement Surgery ◽  
Deep Vein

OBJECTIVE: To compare the use of healthcare services in patients receiving enoxaparin, a low molecular weight heparin versus those receiving unfractionated heparin as prophylaxis against deep-vein thrombosis (DVT) following total hip replacement surgery. DESIGN: Economic evaluation undertaken in conjunction with a randomized, open-label, parallel group, Phase III clinical trial. SETTING: 32 US acute-care hospitals. PATIENTS: 607 patients undergoing elective total hip replacement. INTERVENTIONS: Enoxaparin 30 mg q12h, enoxaparin 40 mg qd, or unfractionated heparin 5000 units q8h started within 24 hours following surgery and continued for 7 days. MAIN OUTCOME MEASURES: (1) Use of selected tests and treatments for DVT; (2) use of selected tests and treatments related to post-operative bleeding; (3) length of stay in hospital; and (4) readmissions to hospital within 14 days. RESULTS: Although the use of selected tests and treatments related to DVT or postoperative bleeding did not differ significantly between the three treatment groups, mean length of stay in the hospital (following the start of study therapy) was shorter among patients receiving enoxaparin 30 mg (9.5 days; p=0.01) or 40 mg (9.9 days; p<0.05) than those receiving unfractionated heparin (11.3 days). There was also a trend toward fewer hospital readmissions in both of the enoxaparin groups. CONCLUSIONS: Compared with unfractionated heparin, use of enoxaparin following total hip replacement may decrease the risk of DVT and length of hospital stay.

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