SEARCH · PubMed Health

Results for “Dalteparin”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1996

Use of low molecular weight heparin (dalteparin), once daily, for the treatment of deep vein thrombosis. A feasibility and health economic study in an outpatient setting. Swedish Venous Thrombosis Dalteparin Trial Group.

OBJECTIVES: To test the safety and feasibility of treating deep vein thrombosis (DVT) in an outpatient setting, using the low molecular weight heparin dalteparin, to calculate the potential and actual cost reductions achievable as a result of such a treatment regimen. DESIGN: An open, nonrandomized, multicentre trial. SETTING: Fourteen hospitals in central Sweden. SUBJECTS: Ambulant patients, aged 18 years or older. with symptomatic DVT in the leg, diagnosed using phlebography or ultrasound (Duplex-Doppler). INTERVENTIONS: Dalteparin (Fragmin) at a fixed dose of 200 i.u. kg-1 body weight, was administered once daily subcutaneously for at least 4 consecutive days. Treatment with warfarin was initiated from the first day of dalteparin administration. Outpatient treatment was encouraged whenever possible Financial calculations were performed independently at two hospitals, giving an average cost for all actions. OUTCOME MEASURES: Increasing severity of symptoms (or thromboembolic recurrences during the 3-months follow-up period), pulmonary embolism (PE), bleeding events, and death during the initial phase and follow-up period. RESULTS: Of 434 patients, 35% and 64% were treated in hospital within 24 and 72 h, respectively, and thereafter as outpatients. The overall frequency of serious complications was 0.92% (exact 95% confidence interval, 0.25-2.35%) during the initial phase and one patient suffered a PE and three patients had a recurrent DVT during the follow-up period. A cost reduction of 2705529 Swedish crowns (34.5%) was achieved in this study compared with traditional in-patient treatment. CONCLUSIONS: Dalteparin, administered subcutaneously, once daily, for the initial treatment of DVT yields large cost reductions and is well tolerated and effective in an outpatient setting.

Aged↗

PubMed1999

Enoxaparin and dalteparin in unstable angina: new indication. Enoxaparin: a reference treatment. Dalteparin: no better than unfractionated heparin.

(1) Enoxaparin and dalteparin are the only low-molecular-weight heparins so far approved for the treatment of unstable angina and non Q-wave myocardial infarction. (2) In two trials involving over 7,000 patients with unstable angina or non Q-wave myocardial infarction, the enoxaparin + aspirin combination was more effective than the unfractionated heparin + aspirin combination in reducing the risk of death, myocardial infarction or angina relapse. (3) In the same indication another trial showed no significant difference between the dalteparin + aspirin combination and the unfractionated heparin + aspirin combination on the basis of the same end point. (4) The dose must be calculated precisely according to bodyweight, as there is a severe risk of bleeding if the recommended dose is exceeded. (5) Continued enoxaparin therapy after clinical stabilisation has no supplementary benefit compared with aspirin alone.

Angina, Unstable↗

PubMed1997

Dalteparin: a low-molecular-weight heparin.

OBJECTIVE: To discuss the chemistry, pharmacology, and pharmacokinetics of dalteparin, a low-molecular-weight heparin (LMWH), and to review the comparative clinical trial data evaluating the efficacy and safety of dalteparin and unfractionated heparin (UH) for the prophylaxis and treatment of venous thromboembolism. DATA SOURCES: A MEDLINE search identified pertinent English-language publications on dalteparin and venous thromboembolism. Key search terms were dalteparin, Fragmin, LMWH, and venous thromboembolism. The search was supplemented by review articles, articles obtained from the bibliographies of the review articles, and the dalteparin approval database. STUDY SELECTION: The most pertinent studies describing the pharmacology and pharmacokinetics of dalteparin in humans were selected; all abstracts and clinical evaluating the use of dalteparin for antithrombotic therapy were reviewed. Review articles by authors of international reputation were selected. DATA EXTRACTION: Pertinent information from the review articles on the pharmacology of LMWHs and UH was summarized. Clinical trial data were extracted for study design, patient demographics, therapeutic regimens, methods of evaluation, and outcomes. DATA SYNTHESIS: Dalteparin is an LMWH indicated for patients undergoing abdominal surgery who are considered to be at risk for deep-vein thrombosis (DVT), which may lead to pulmonary embolism (PE). In this population, numerous clinical trials have demonstrated comparable efficacy between dalteparin and fixed-dose UH for DVT prophylaxis. Dalteparin has a predictable dose response and can be administered as a standard single daily subcutaneous dose for all patients. In therapeutic doses, dalteparin does not alter coagulation tests and therefore does not require routine laboratory monitoring, in contrast with adjusted-dose UH. Bleeding risks with dalteparin are comparable with and possibly less than those associated with UH. Preliminary studies suggest that dalteparin may be effective for other indications, including DVT prophylaxis for hip replacement surgery and the treatment of DVT and PE. Comparative cost-effectiveness data are not yet available. CONCLUSIONS: Dalteparin is the second LMWH to receive approval by the Food and Drug Administration. Dalteparin is indicated for prophylaxis against DVT in patients undergoing abdominal surgery. Clinical studies have shown that single daily doses of dalteparin provide a safe and effective alternative to fixed-dose UH therapy. Additional studies are needed to determine the cost-effectiveness of dalteparin compared with UH and other LMWHs.

Abdomen↗

PubMed1999

A controlled trial of low-molecular-weight heparin (dalteparin) versus unfractionated heparin as anticoagulant during continuous venovenous hemodialysis with filtration.

OBJECTIVE: To compare the efficacy, safety, and cost of fixed-dose low-molecular-weight heparin (dalteparin) with adjusted-dose unfractionated heparin as anticoagulant for continuous hemofiltration. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: University-affiliated adult intensive care unit PATIENTS: All patients requiring continuous hemofiltration for acute renal failure or systemic inflammatory response syndrome (SIRS) were eligible. Fifty-seven patients were enrolled. Eleven were excluded, seven because of major protocol violations and four died before hemofiltration. INTERVENTIONS: Patients received continuous venovenous hemodialysis with filtration with prefilter replacement at 500 mL/hr and countercurrent dialysate at 1000 mL/hr. Filters were primed with normal saline containing anticoagulant. Dalteparin-treated patients received a commencement bolus of 20 units/kg and a maintenance infusion at 10 units/kg/hr. Heparin-treated patients received a commencement bolus of 2000-5000 units and a maintenance infusion at 10 units/kg/hr, titrated to achieve an activated partial thromboplastin time in the patient of 70-80 secs. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure--time to failure of the hemofilter--was compared using survival analysis. Twenty-two patients (13 with acute renal failure and nine with SIRS; total, 41 filters) were randomized to heparin. Twenty-five patients (16 with acute renal failure and nine with SIRS; total, 41 filters) were randomized to dalteparin. Mean (SE) activated partial thromboplastin time in the heparin group was 79 (4.3) secs. Mean (SE) anti-factor-Xa activity in the six patients given dalteparin who were assayed was 0.49 (0.07). Mean (SE) prehemofiltration platelet count was 225 (35.5) x 10(9) for heparin and 178 (18.1) x 10(9) for dalteparin (p = .24, unpaired Student's t-test). Mean (SE) prehemofiltration hemoglobin was 11.4 (0.61) g/dL for heparin and 10.6 (0.38) g/dL for dalteparin (p = .31, unpaired Student's t-test). PRIMARY OUTCOME: There was no significant difference in the time to failure between the two groups (p = .75, log rank test). For dalteparin, Kaplan-Meier (K-M) mean (SE) time to failure of the hemofilter was 46.8 (5.03) hrs. For heparin, K-M mean (SE) time to failure was 51.7 (7.51) hrs. The 95% CI for difference in mean time to failure was -13 to 23 hrs. The power of this study to detect a 50% change in filter life was >90%. SECONDARY OUTCOMES: Mean (SE) reduction in platelet count during hemofiltration was 63 (25.8) x 10(9) for heparin and 41.8 (26.6) x 10(9) for dalteparin (p = .57, unpaired Student's t-test). Eight patients given dalteparin and four patients given heparin had screening for heparin-induced thrombocytopenia; three of the dalteparin patients and one of the heparin patients were positive (p = 1.0, Fisher's exact test). There were three episodes of trivial bleeding and two episodes of significant bleeding for dalteparin, and there were three episodes of trivial bleeding and four episodes of significant bleeding for heparin (p = .53, chi-square test). The mean (SE) decrease in hemoglobin concentration during hemofiltration was 0.51 (0.54) g/dL for heparin and 0.28 (0.49) g/dL for dalteparin (p = .75, unpaired Student's t-test). The mean (SE) packed-cell transfusion volume during hemofiltration was 309 (128) mL for heparin and 290 (87) mL for dalteparin (p = .90, unpaired Student's t-test). Daily costs, including coagulation assays, of hemofiltration were approximately 10% higher using dalteparin than with heparin. CONCLUSIONS: Fixed-dose dalteparin provided identical filter life, comparable safety, but increased total daily cost compared with adjusted-dose heparin. Unfractionated heparin remains our anticoagulant of choice for continuous hemofiltration in intensive care.

Acute Kidney Injury↗

PubMed2006

Dalteparin, a low molecular weight heparin, attenuates inflammatory responses and reduces ischemia-reperfusion-induced liver injury in rats.

OBJECTIVE: To examine whether dalteparin, a low molecular weight heparin, prevents hepatic damage by inhibiting leukocyte activation, we analyzed its effect on ischemia/reperfusion (I/R) injury of rat liver in which activated leukocytes play a critical role. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Male Wistar rats weighing 220-280 g. INTERVENTIONS: Hepatic damage was evaluated by changes in serum transaminase concentrations after I/R. Coagulation abnormalities were evaluated by changes in serum concentrations of fragment E of fibrin and fibrinogen degradation products after I/R. Hepatic tissue blood flow was measured by laser-Doppler flow meter. Hepatic edema was evaluated by determination of the change in the wet/dry tissue weight ratio. Rats were intravenously injected with dalteparin or unfractionated heparin (300 units/kg) and subcutaneously injected with DX9056a, a selective inhibitor of activated factor X (3 mg/kg). To determine whether dalteparin inhibits leukocyte activation, we examined the effect of dalteparin on hepatic concentrations of interleukin-12, tumor necrosis factor-alpha, and hepatic myeloperoxidase activity after I/R in vivo. In addition, we examined increases in tumor necrosis factor-alpha production in rat monocytes and in intracellular calcium concentrations in neutrophils in vitro. We also examined the effect of dalteparin on endothelial production of prostacyclin using isolated rat hepatic sinusoidal cells in vitro. MEASUREMENTS AND MAIN RESULTS: Intravenous administration of dalteparin inhibited increases in serum levels of both transaminases and serum concentrations of fragment E of fibrin and fibrinogen degradation products in animals subjected to hepatic I/R. Hepatic tissue blood flow after reperfusion was increased by dalteparin. Dalteparin inhibited hepatic edema, increases in hepatic tissue levels of interleukin-12 and tumor necrosis factor-alpha, and accumulation of neutrophils in animals subjected to hepatic I/R. Neither DX9065a nor unfractionated heparin showed any therapeutic effects, despite potent inhibition of increases in serum levels of fragment E of fibrin and fibrinogen degradation products. Neither monocytic tumor necrosis factor-alpha production nor neutrophil activation was inhibited by dalteparin in vitro. Dalteparin enhanced the hepatic I/R-induced increases in hepatic tissue levels of 6-keto-prostaglandin (PG) F1alpha, a stable metabolite of prostacyclin, which is capable of inhibiting monocytic tumor necrosis factor-alpha production. Pretreatment with indomethacin completely reversed both of the therapeutic effects of dalteparin, whereas pretreatment with NS-398, a selective inhibitor of cyclooxygenase-2, did not. Dalteparin did not directly increase the endothelial production of prostacyclin in vitro. CONCLUSION: Dalteparin might reduce I/R-induced liver injury in rats by attenuating inflammatory responses. These therapeutic effects might be independent of its anticoagulant activity but dependent on its capacity to enhance endothelial production of prostacyclin via cyclooxygenase-1 activation. Furthermore, the mechanism or mechanisms by which dalteparin promotes the endothelial production of prostacyclin in vivo might involve unknown factors other than endothelial cells.

6-Ketoprostaglandin F1 alpha↗

PubMed2000

Dalteparin: an update of its pharmacological properties and clinical efficacy in the prophylaxis and treatment of thromboembolic disease.

UNLABELLED: Dalteparin is a low molecular weight heparin (LMWH) with a mean molecular weight of 5000. Compared with unfractionated heparin (UFH), the drug has markedly improved bioavailability and increased plasma elimination half-life, and exerts a greater inhibitory effect on plasma activity of coagulation factor Xa relative to its effects on other coagulation parameters. Dalteparin also has less lipolytic activity than UFH. Dalteparin 2500U once daily subcutaneously is of similar antithrombotic efficacy to UFH 5000IU twice daily, and 2 studies have shown superiority over UFH 2 or 3 times daily of dalteparin 5000U once daily in patients requiring surgical thromboprophylaxis. After total hip arthroplasty, dalteparin was superior to adjusted-dosage warfarin and was of greater thromboprophylactic efficacy when given for 35 than for 7 days. Intravenous or subcutaneous dalteparin is as effective as intravenous UFH when given once or twice daily in the initial management of established deep vein thrombosis (DVT). The drug is also effective in long term home treatment. Dalteparin has been shown to be effective in combination with aspirin in the management of unstable coronary artery disease (CAD), with composite end-point data from 1 study suggesting benefit for up to 3 months. Current data indicate potential of the drug in the management of acute myocardial infarction (MI). Dalteparin is also of similar efficacy to UFH, with a single bolus dose being sufficient in some patients, in the prevention of clotting in haemodialysis and haemofiltration circuits. Pharmacoeconomic data indicate that overall costs relative to UFH from a hospital perspective can be reduced through the use of dalteparin in patients receiving treatment for venous thromboembolism. Dalteparin has also been shown to be cost effective when used for surgical thromboprophylaxis. Overall, rates of haemorrhagic complications in patients receiving dalteparin are low and are similar to those seen with UFH. CONCLUSIONS: Dalteparin is effective and well tolerated when given subcutaneously once daily in the prophylaxis and treatment of thromboembolic disease. The simplicity of the administration regimens used and the lack of necessity for laboratory monitoring facilitate home or outpatient treatment and appear to translate into cost advantages from a hospital perspective over UFH or warfarin. Dalteparin also maintains the patency of haemodialysis and haemofiltration circuits, with beneficial effects on blood lipid profiles and the potential for prophylaxis with a single bolus injection in some patients. Data are also accumulating to show dalteparin to be an effective and easily administered alternative to UFH in patients with CAD.

Blood Coagulation↗

PubMed2005

Cost effectiveness of dalteparin for preventing venous thromboembolism in abdominal surgery.

INTRODUCTION: Patients undergoing abdominal surgeries face substantial risk of experiencing venous thromboembolic events in the perioperative period. The low-molecular-weight heparin dalteparin sodium is clinically effective in reducing the incidence of venous thromboembolism (VTE) in these patients. Dalteparin may be used in low (2500 units [U]) and high (5000 U) once-daily doses for this indication. However, the cost effectiveness of dalteparin 5000 U compared with dalteparin 2500 U and unfractionated heparin (UFH) for this indication has not been studied. OBJECTIVE: To conduct a cost-utility analysis to evaluate the cost effectiveness of dalteparin compared with UFH for preventing VTE in patients undergoing elective abdominal surgery. METHODS: A Markov model, from a healthcare perspective, was constructed to evaluate the cost effectiveness of dalteparin 5000 U and dalteparin 2500 U compared with UFH. A 69-year-old mixed sex patient population was studied using pooled probabilities of clinical outcomes from randomised, controlled trials. Cost data were mostly derived from Medicare reimbursement, in year 2002-03 values. Cost effectiveness was measured as cost per QALY gained over the patient's lifetime. RESULTS: Total costs for patients given UFH, dalteparin 2500 U and dalteparin 5000 U were US45,855 dollars, US45,882 dollars and US46,308 dollars, respectively, while QALYs were 9.5603, 9.5632 and 9.5811, respectively. Hence, the incremental cost effectiveness of dalteparin 5000 U over dalteparin 2500 U and UFH was US23,799 dollars/QALY and US21,779 dollars/QALY gained, respectively. Similarly, cost effectiveness for dalteparin 2500 U over UFH was US9310 dollars/QALY gained. Univariate sensitivity analysis showed that dalteparin 5000 U maintained its cost effectiveness (incremental cost-effectiveness ratio [ICER] or =90% patients receive the benefit of the medication, policy makers would need to commit substantially more resources than suggested by the baseline ICERs.

Abdomen↗

PubMed2003

The activated clotting time can be used to monitor the low molecular weight heparin dalteparin after intravenous administration.

OBJECTIVES: This study was designed to compare the dose response of dalteparin versus unfractionated heparin (UFH) on the activated clotting time (ACT), and to determine whether the ACT can be used to monitor intravenous (IV) dalteparin during percutaneous coronary intervention (PCI). BACKGROUND: The use of low molecular weight heparin (LMWH) during PCI has been limited by the presumed inability to monitor its anticoagulant effect using bedside assays. METHODS: This study was performed in three phases. In vitro, ACTs were measured on volunteer (n = 10) blood samples spiked with increasing concentrations of dalteparin or UFH. To extend these observations in vivo, ACTs were then measured in patients (n = 15) who were sequentially treated with IV dalteparin and then UFH. Finally, a larger monitoring study was undertaken involving patients (n = 110) who received dalteparin 60 or 80 international U (IU)/kg alone or followed by abciximab. We measured ACT (Hemochron), activated partial thromboplastin time (aPTT), plasma anti-Xa and anti-IIa levels, tissue factor pathway inhibitor (TFPI) concentration, and plasma dalteparin concentration. RESULTS: Dalteparin induced a significant rise in the ACT with a smaller degree of variance as compared to UFH. Five min after administration of IV dalteparin 80 IU/kg the ACT increased from 125 s (122 s, 129 s) to 184 s (176 s, 191 s) (p < 0.001). The aPTT, anti-Xa and anti-IIa activities, and TFPI concentration also demonstrated significant increases following IV dalteparin. CONCLUSIONS: The ACT and aPTT are sensitive to IV dalteparin at clinically relevant doses. These data suggest that the ACT may be useful in monitoring the anticoagulant effect of intravenously administered dalteparin during PCI.

Aged↗

PubMed1996

Dalteparin sodium. A review of its pharmacology and clinical use in the prevention and treatment of thromboembolic disorders.

The low molecular weight heparin (LMWH) dalteparin sodium is notable for its improved pharmacokinetic characteristics (chiefly increased bioavailability and plasma elimination half-life) compared with unfractionated heparin (UFH). These properties enable the drug to be given subcutaneously as a single daily dose, compared with the 8- to 12-hourly regimens necessary with UFH. Dalteparin sodium also appears to exert a greater inhibitory effect than UFH on plasma activity of coagulation factor Xa relative to its effects on clotting times [usually expressed as activated partial thromboplastin time (APTT)] and activity of factor IIa. It is not associated with any clinically significant effects on the fibrinolytic system and may have less lipolytic activity than UFH. Extensive clinical studies have been conducted to compare the antithrombotic efficacy of dalteparin sodium with that of UFH in surgical thromboprophylaxis, treatment of established deep vein thrombosis (DVT) and the anticoagulation of patients undergoing haemodialysis and haemofiltration. The majority of trails of patients receiving thromboprophylactic heparin perioperatively have shown similar efficacy of dalteparin sodium and UFH in the prevention of DVT and pulmonary embolism (PE), although 2 groups of investigators reported superior antithrombotic potency for dalteparin sodium. The two types of heparin appear similarly effective in the management of established DVT and the maintenance of the extracorporeal circulation in haemodialysis circuits. Dalteparin sodium has also shown clinical benefit in the management of patients with unstable angina or non-Q-wave myocardial infarction. The overall incidence of haemorrhagic complications observed with daltparin sodium therapy is no greater than that associated with UFH, and data suggest that perioperative transfusion requirements and frequency of bleeding are lower after dalteparin sodium. The antithrombotic efficacy of dalteparin sodium is at least equivalent to that of UFH, although further clinical comparisons with other LMWHs are required. Further studies are also needed to clearly define any advantages of dalteparin sodium over UFH (and other antithrombotics) with regard to the incidence of haemorrhagic complications. The drug has also shown clinical efficacy in the prevention of myocardial infarction and death in patients with unstable coronary artery disease. In addition, there may be cost advantages attached to the once-daily subcutaneous regimen of dalteparin sodium, but this requires further examination. Thus, dalteparin sodium is an effective antithrombotic agent for perioperative thromboprophylaxis, the management of established DVT, and the anticoagulation of patients undergoing haemodialysis.

Anticoagulants↗

PubMed2006

A randomized pilot study of dalteparin versus unfractionated heparin during percutaneous coronary interventions.

BACKGROUND: Direct comparison of low-molecular-weight heparin, dalteparin, with unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) is limited. This study examined the relative effects of dalteparin and UFH on coagulation and angiographic and clinical indices during PCI. METHODS: This was a double-blind randomized study, stratified by planned glycoprotein IIb/IIIa inhibitor use. Both UFH and dalteparin were administered as an intra-arterial bolus immediately before PCI. RESULTS: All randomized patients received the assigned study drug and underwent PCI. Mean activated clotting time levels were 344 seconds for UFH and 234 seconds for dalteparin (P < .0001). Anti-factor Xa levels were higher for dalteparin at 30 minutes (UFH 1.3 IU/mL vs dalteparin 1.7 IU/mL, P = .005)) and at 4 hours (UFH 0.27 IU/mL vs dalteparin 0.69 IU/mL, P < .0001). Angiographic success was > 90% in both groups, and angiographic complications were similar (UFH 2.5% vs dalteparin 3.8%). The composite of death, myocardial infarction, target vessel revascularization, or bailout glycoprotein IIb/IIIa at hospital discharge was 13.7% in the UFH group and 13.1% in the dalteparin group (P = not significant). There were 2 major bleedings requiring transfusion, both occurring in the UFH group. CONCLUSIONS: This study suggests that a single intra-arterial bolus of low-molecular-weight heparin without monitoring is feasible and warrants further investigation as an alternative to UFH during PCI.

Angioplasty, Balloon, Coronary↗

PubMed1997

Randomized trial of low molecular weight heparin (dalteparin) in prevention of left ventricular thrombus formation and arterial embolism after acute anterior myocardial infarction: the Fragmin in Acute Myocardial Infarction (FRAMI) Study.

OBJECTIVES: The present trial investigated the efficacy and safety of dalteparin in the prevention of arterial thromboembolism after an acute anterior myocardial infarction (MI). BACKGROUND: Left ventricular (LV) thrombus formation is associated with increased risk of arterial embolism in patients with an acute MI. Thrombolytic and antiplatelet therapy do not prevent thrombus formation. METHODS: A total of 776 patients were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of subcutaneous dalteparin (150 IU/kg body weight every 12 h during the hospital period). Thrombolytic therapy and aspirin were administered in 91.5% and 97.6% of patients, respectively. The primary study end point was the composite of thrombus formation diagnosed by echocardiography and arterial embolism on day 9 +/- 2. RESULTS: Of 517 patients with echocardiographic recordings available for end point analysis, thrombus formation or embolism, or both, was found in 59 (21.9%) of 270 patients (59 with thrombus, none with embolism) in the placebo group and 35 (14.2%) of 247 patients (34 with thrombus, 1 with embolism) in the dalteparin group (p = 0.03). The risk reduction of thrombus formation associated with dalteparin treatment was 0.63 (95% confidence interval 0.43 to 0.92, p = 0.02). Analyses of all randomized patients (388 in each group) revealed no significant difference between the placebo and dalteparin groups with respect to arterial embolism (6 vs. 5 patients), reinfarction (8 vs. 6 patients) and mortality rates (23 vs. 23 patients, p = NS for all). Dalteparin was associated with an increased risk of hemorrhage: major in 11 dalteparin group patients (2.9%) verus 1 placebo group patient (0.3%, p = 0.006); minor in 52 dalteparin group patients (14.8%) versus 8 placebo group patients (1.8%, p < 0.001). CONCLUSIONS: Dalteparin treatment significantly reduces LV thrombus formation in acute anterior MI but is associated with increased hemorrhagic risk.

Aged↗

PubMed2003

Low-molecular-weight heparin (dalteparin) effectively prevents thrombosis in a rat model of deep arterial injury.

Unfractionated heparin is often used to prevent thrombosis in microvascular surgery, but a major drawback of heparin therapy is increased bleeding. Low-molecular-weight heparins prevent venous thrombosis as effectively as heparin and have better bioavailability and a longer plasma half-life, which explains the increased use of low-molecular-weight heparins as substitutes for heparin in clinical practice. However, the ability of low-molecular-weight heparins to prevent arterial thrombosis has been debated. In this study, the authors compared the antithrombotic and antihemostatic effects of heparin and the low-molecular-weight heparin dalteparin in a rat model of arterial thrombosis. A segment of the left common carotid artery was isolated between vascular clamps and opened longitudinally. An endarterectomy was performed and the arteriotomy was closed with a running suture. The antithrombotic effect (vascular patency 31 minutes after reperfusion) and the surgical bleeding were measured. Groups of 10 rats were treated in a blind, random fashion with intravenous injection of one of the following substances 1 minute before clamp release. Three groups received a bolus of heparin (20, 60, or 180 IU anti-factor Xa/kg), three groups received dalteparin (60, 180, or 540 IU anti-factor Xa/kg), and one group was treated with vehicle (saline). Heparin 180 IU/kg produced a distinct antithrombotic effect compared with the control group (p = 0.03), but it also significantly increased the surgical bleeding to 2.0 g compared with 1.5 g in the control group (medians, p = 0.01). Dalteparin 180 and 540 IU/kg also produced a powerful antithrombotic effect (p = 0.01 and p = 0.03, respectively). In contrast to heparin, 180 IU/kg dalteparin did not increase the surgical bleeding (median, 1.5 g; p = 0.37 versus controls). Dalteparin 540 IU/kg increased the median surgical bleeding to 2.6 g (p = 0.06 versus controls). The nonsignificant difference may be explained by the great interindividual variation of surgical bleeding in the high-dose dalteparin group. Dalteparin prevented arterial thrombosis as effectively as unfractionated heparin. In contrast to heparin, dalteparin did not increase the surgical bleeding, which indicates that dalteparin instead of heparin can be used to prevent thrombosis in microvascular surgery.

Animals↗

PubMed2005

Life-threatening hemorrhage after dalteparin therapy in a patient with impaired renal function.

Dalteparin and other low-molecular-weight heparins are frequently used for the treatment of deep vein thrombosis and for other indications. Unlike unfractionated heparin (UFH), dalteparin is mainly cleared through the kidney; therefore, it can accumulate in patients with impaired renal function, increasing the risk of hemorrhage. An 84-year-old woman with chronic renal failure was hospitalized because of stenosis of a femorofibular bypass in her right leg. Peripheral transluminal angioplasty was performed successfully. Later the same day, Doppler sonography revealed deep vein thrombosis of the left lower leg. Treatment with dalteparin was started. The patient was discharged home 3 days later, with dalteparin to be continued at home. One day later, the patient was rehospitalized because of a pronounced hematoma on her flank. Her hemoglobin level had dropped to 5.5 g/dl. Treatment with dalteparin was stopped, and protamine 2500 U and two transfusions of packed red blood cells were administered. Treatment with UFH and oral anticoagulants were started because of a persistent risk for venous thrombosis. Thereafter, the patient's hemoglobin level remained stable, and no further bleeding episodes occurred. As long as systematic studies of the efficacy and safety of dalteparin in patients with severe renal impairment are lacking, dalteparin should be avoided or used only with close monitoring of antifactor Xa activity in these patients. As an alternative, UFH can be used because monitoring of UFH is well established and easier than it is with dalteparin. Renal impairment does not notably influence the short elimination half-life of UFH, which unlike that of dalteparin or other low-molecular-weight heparins allows for rapid dosage adjustments to prevent hemorrhage.

Aged↗

PubMed2000

Dalteparin new treatment duration: new dosage. Is prolonged prophylaxis needed?

(1) In the prevention of deep venous thrombosis after hip surgery, the recommended treatment period with dalteparin has been extended from seven days to 35 days. (2) The clinical file is based on two double-blind trials comparing dalteparin administered for 35 days with dalteparin administered for seven days followed by a placebo, in a total of 546 patients. (3) No clinical trials have compared prolonged dalteparin prevention to dalteparin for one week followed by oral anticoagulant therapy. (4) Clinical vascular events were infrequent between days 7 and 35. There was one death due to pulmonary embolism in the placebo group. One patient on dalteparin died, possibly because of a subdural haematoma discovered at autopsy. (5) Prolonged dalteparin prophylaxis necessitates laboratory monitoring to detect thrombocytopenia. (6) Cost-effectiveness studies of dalteparin administration for 35 days versus dalteparin for seven days followed by oral anticoagulants, are required.

Anticoagulants↗

PubMed1995

Comparison of the pharmacokinetic profiles of three low molecular mass heparins--dalteparin, enoxaparin and nadroparin--administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism).

The present trial was designed to comparatively investigate the pharmacokinetic profile and evaluate the apparent bioavailability pattern of three already marketed low molecular mass heparins (LMMHs): dalteparin (Fragmin), nadroparin (Fraxiparin), and enoxaparin (Lovenox) given by subcutaneous route. The study was carried out in 20 healthy young volunteers given, according to a cross over design, a single subcutaneous injection of the doses recommended for the prophylaxis of deep vein thrombosis (commercial preparations, prefilled syringes): dalteparin 2,500 IU (= 2,500 IU anti-Xa), nadroparin 7,500 ICU (= 3,075 IU anti-Xa), enoxaparin 20 mg (= 2,000 IU anti-Xa) and enoxaparin 40 mg (= 4,000 IU anti-Xa). Of the markers used, activated partial thromboplastin time (APTT), thrombin clotting time (TCT), Heptest, anti-thrombin (aIIa) activity and anti-Xa (aXa) activity, the most pertinent parameter (from a biodynamic viewpoint) is plasma aXa activity. We demonstrated that dalteparin, nadroparin and enoxaparin exhibit statistically significantly different pharmacokinetic and overall disposition patterns. Normalized to the same injected dose (1,000 IU aXa), the relative actual amount of plasma anti-Xa activity generated by enoxaparin is 1.48 times greater (p < 0.001) than that of nadroparin and 2.28 times greater (p < 0.001) than that of dalteparin while the plasma amount induced by nadroparin is 1.54 times greater (p < 0.001) than that of dalteparin. The apparent total body clearance of enoxaparin doses (CL/F = 16.7 +/- 5.5 and 13.8 +/- 3.2 ml/min) is significantly smaller than those of nadroparin (CL/F = 21.4 +/- 7.0 ml/min; p < 0.01) and dalteparin (CL/F = 33.3 +/- 11.8 ml/min; p < 0.001) while dalteparin apparent clearance is about 1.5-fold greater (p < 0.001) than that of nadroparin. These LMMHs also differ by their renal excretion pattern: more fragments exhibiting an anti-Xa activity are recovered in urine following enoxaparin doses (6.4 and 8.7% of the dose, respectively) than following nadroparin (3.9%) and dalteparin (3.4%) injection. These differences in the disposition profiles explain why the apparent elimination half life t1/2 values of the LMMHs compared here are different: dalteparin: 2.8 h; nadroparin: 3.7 h; and enoxaparin: 4.1 h. Whether or not these differences may contribute to explain the different safety/efficacy balance of each of these antithrombotic medications remains to be discussed and needs further studies.

Adolescent↗

PubMed1996

Once-daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis.

The aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin, a low molecular weight heparin, with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis (DVT). Patients were included if they had deep venous thrombosis distal to inguinal ligament and were randomised either before, if it was considered necessary, or after phlebographic verification of the diagnosis. There was no pre-inclusion treatment with unfractionated heparin. One hundred and twenty patients received dalteparin, administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg, and 133 patients received a continuous intravenous infusion of unfractionated heparin (UFH). Oral anticoagulation was started on the first or second day, and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range (2 < INR < 3) on two consecutive days. Control phlebograms were taken within 4 days, thereafter. There were no significant differences between the two initial treatment groups in improvements in Marder score. Two major bleeding events occurred in the UFH group versus none in the dalteparin group. One patient in each group experienced clinically significant pulmonary embolism. During a mean follow-up period of 6.9 +/- 1.5 months, recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group. These results confirm those of a previous study on dalteparin in the initial treatment of DVT, and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament. The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH. Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised, studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted.

Acute Disease↗

PubMed2000

Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. The North American Fragmin Trial Investigators.

BACKGROUND: Based on the current understanding that venous thrombosis starts perioperatively, administration of just-in-time low-molecular-weight heparin immediately before or in close proximity after hip arthroplasty may be more effective than usual clinical practice. METHODS: We performed a randomized, double-blind trial comparing subcutaneous dalteparin sodium given once daily immediately before or early after surgery with the use of postoperative warfarin sodium in 1472 patients undergoing elective hip arthroplasties. The primary end point was deep vein thrombosis detected using contrast venography performed after surgery (mean, 5. 7 days) in each group. RESULTS: The frequencies of deep vein thrombosis for patients with interpretable venograms receiving preoperative and postoperative dalteparin for all deep vein thrombosis were 36 (10.7%) of 337 (P<.001) and 44 (13.1%) of 336 (P<.001), respectively, vs 81 (24.0%) of 338 for warfarin; for proximal deep vein thrombosis, 3 (0.8%) of 354 (P =.04) and 3 (0.8%) of 358 (P =.03), respectively, vs 11 (3.0%) of 363. Relative risk reductions for the dalteparin groups ranged from 45% to 72%. Symptomatic thrombi were less frequent in the preoperative dalteparin group (5/337 patients [1.5%]) vs the warfarin group (15/338 patients [4.4%]) (P =.02). Serious bleeding was similar among groups. Increased major bleeding at the surgical site was observed for patients receiving preoperative dalteparin vs warfarin (P =.01). CONCLUSIONS: A modified dalteparin regimen in close proximity to surgery resulted in substantive risk reductions for all and proximal deep vein thrombosis, compared with warfarin therapy. Such findings have not been observed with low-molecular-weight heparin therapy commenced 12 hours preoperatively or 12 to 24 hours postoperatively vs oral anticoagulants. Increased major but not serious bleeding occurred in patients receiving preoperative dalteparin. Dalteparin therapy initiated postoperatively provided superior efficacy vs warfarin without significantly increased overt bleeding.

Anticoagulants↗

PubMed2005

Efficacy and safety of fixed low-dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial.

BACKGROUND: We were concerned that a fixed rather than a weight-based dosing regimen of dalteparin sodium to prevent venous thromboembolism (VTE) might result in decreased efficacy in obese patients and decreased safety in elderly patients. METHODS: We retrospectively performed subgroup analyses using the database from the Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients (PREVENT) Trial, a study of 3706 hospitalized, medically ill patients randomized to receive either dalteparin sodium, 5000 U/d, or placebo. The primary end point was a composite of symptomatic VTE, fatal pulmonary embolism, sudden death, or asymptomatic proximal deep venous thrombosis by day 21. Obesity was defined as a body mass index (calculated as weight in kilograms divided by the square of height in meters) of 30 or greater for men and 28.6 or greater for women. RESULTS: Overall, 1118 patients (30.4%) were obese and 1226 (33.3%) were 75 years or older. In obese patients, the primary end point occurred in 2.8% of the dalteparin and in 4.3% of the placebo groups (relative risk, 0.64; 95% confidence interval [CI], 0.32-1.28). In patients 75 years or older, the primary end point was reported in 4.2% of the dalteparin and in 8.0% of the placebo groups (relative risk, 0.52; 95% CI, 0.31-0.87). The dalteparin effect for the primary end point (odds ratio, 0.51; 95% CI, 0.32-0.82) was not attenuated when adjusted for age, sex, obesity, history of VTE, and varicose veins. Dalteparin was not associated with an increase in major hemorrhage by day 21 in obese (0% vs 0.7% placebo; P>.99) and in elderly (1.1% vs 0.7%; P=.12) patients. CONCLUSION: Our findings suggest that a fixed low dose of dalteparin sodium of 5000 U/d is effective and safe in preventing VTE in obese and elderly hospitalized medical patients.

Aged↗