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Critical Care Medicine Jul 2006
Topics: Animals; Anticoagulants; Dalteparin; Fibrinolytic Agents; Liver; Liver Diseases; Rats; Reperfusion Injury; Syndrome
PubMed: 16801867
DOI: 10.1097/01.CCM.0000221924.87300.25 -
Lancet (London, England) Feb 2015
Topics: Dalteparin; Female; Fibrinolytic Agents; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombophilia
PubMed: 25706214
DOI: 10.1016/S0140-6736(15)60285-9 -
Arzneimittel-Forschung Aug 1998The inhibitory effect on the activated coagulation factor X activity (anti-Xa activity) in plasma and urine of danaparoid sodium (DAS, CAS 9005-49-6) was compared with...
Pharmacokinetics of danaparoid sodium, dalteparin sodium and heparin determined by inhibitory effect on the activated coagulation factor X activity after single intravenous administration in rabbits.
The inhibitory effect on the activated coagulation factor X activity (anti-Xa activity) in plasma and urine of danaparoid sodium (DAS, CAS 9005-49-6) was compared with that of dalteparin sodium (DLS, CAS 9041-08-1) and heparin (CAS 9005-49-6) after single intravenous administration at a dose of 640 anti-Xa U/kg to male rabbits. The elimination of half-life of DAS was 9.90 h and was 6.0 times longer than that of DLS and 16.5 times longer than that of heparin. The area under the plasma concentration-time curve (AUC) of DAS was 47.13 +/- 14.55 anti-Xa U.h/ml and was 2.4 times larger than that of DLS and 2.9 times larger than that of heparin. The urinary cumulative excretion of anti-Xa activity of DAS and DLS was 42.6 +/- 6.4% and 16.4 +/- 0.8% of dose, respectively, in 24 h after dosing, respectively. But the anti-Xa activity in urine was not detected at any sampling points after administration of heparin. DAS has a longer elimination half-life and a higher renal excretion of anti-Xa activity than that of DLS and heparin. Therefore, in comparison to DLS and heparin, it seems that the anticoagulant activity of DAS has a long duration.
Topics: Animals; Anticoagulants; Blood Coagulation; Chondroitin Sulfates; Dalteparin; Dermatan Sulfate; Drug Combinations; Factor X; Heparin; Heparitin Sulfate; Injections, Intravenous; Male; Rabbits
PubMed: 9748709
DOI: No ID Found -
Lancet (London, England) Nov 2014Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of... (Comparative Study)
Comparative Study Randomized Controlled Trial
Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial.
BACKGROUND
Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia.
METHODS
In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with ClinicalTrials.gov, number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504.
FINDINGS
Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17·1%; 95% CI 11·4-24·2%] vs no dalteparin 27/143 [18·9%; 95% CI 12·8-26·3%]; risk difference -1·8% [95% CI -10·6% to 7·1%)) and on-treatment analysis (dalteparin 28/143 [19·6%] vs no dalteparin 24/141 [17·0%]; risk difference +2·6% [95% CI -6·4 to 11·6%]). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 [19·6%]) than in the no dalteparin group (13/141 [9·2%]; risk difference 10·4%, 95% CI 2·3-18·4; p=0·01).
INTERPRETATION
Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding.
FUNDING
Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn.
Topics: Adult; Dalteparin; Female; Fibrinolytic Agents; Hemorrhage; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Risk Factors; Thrombophilia; Treatment Outcome; Venous Thromboembolism
PubMed: 25066248
DOI: 10.1016/S0140-6736(14)60793-5 -
Nephron. Clinical Practice 2012Low-molecular-weight heparins are being increasingly used as an alternative to unfractionated heparin for anticoagulation of the haemodialysis (HD) circuit. Data on...
BACKGROUND
Low-molecular-weight heparins are being increasingly used as an alternative to unfractionated heparin for anticoagulation of the haemodialysis (HD) circuit. Data on dalteparin use in high-flux HD and haemodiafiltration (HDF) are limited. We examined the safety and efficacy of dalteparin in this setting to enable recommendations on the optimal dose range.
METHODS
This prospective study was conducted in a single dialysis unit. Subjects who had been receiving dalteparin for at least 10 HD sessions were studied. Anti-Xa activity was measured for all subjects at the start of the HD session, at 60 min into HD and at the end of dialysis.
RESULTS
55 subjects were studied. None had detectable anti-Xa activity at the start of the session. Using adequacy criteria based on target anti-Xa activity >0.4 IU/ml at 1 h and <0.4 IU/ml at the end of dialysis, 39 (71%) patients had adequate anticoagulation, 12 (22%) patients were under-anticoagulated and 4 (7%) were over-anticoagulated. The mean dose in the adequately anticoagulated group was 60.7 ± 11.7 IU/kg, in the under-anticoagulated group 39.3 ± 9.6 IU/kg and in the over-anticoagulated group 70.1 ± 14.6 IU/kg. The optimal dose of dalteparin appears to be 60 ± 10 IU/kg, which facilitates the achievement of the target anti-Xa activity in the range of 0.4-0.75 IU/ml at 1 h and <0.4 IU/ml at the session end.
CONCLUSION
Dalteparin is a safe and effective anticoagulant for patients on high-flux HD and HDF. The optimal dose appears to be 60 ± 10 IU/kg. The desirable target range of anti-Xa activity is 0.4-0.75 at 1 h and <0.4 IU/ml at the session end.
Topics: Aged; Anticoagulants; Dalteparin; Female; Hemodiafiltration; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis
PubMed: 23548465
DOI: 10.1159/000348830 -
Pharmacotherapy Jun 2001The three low-molecular-weight heparins (LMWHs) available in the United States have been extensively evaluated for a wide array of indications. Properties associated... (Comparative Study)
Comparative Study Review
The three low-molecular-weight heparins (LMWHs) available in the United States have been extensively evaluated for a wide array of indications. Properties associated with one LMWH cannot be assumed to be the same as those associated with another LMWH, as they are different pharmacologic entities. Therefore, therapeutic interchange of these agents is inappropriate. The pharmacokinetic and pharmacodynamic differences among LMWHs can be explained by comparing methods of preparation, molecular structures, half-lives, antithrombin- and non-antithrombin-mediated actions, effect on thrombus, and dosing interval. The Food and Drug Administration-approved indications and their respective levels of clinical evidence further differentiate these agents. A dichotomy in the results of clinical trials has been observed with the LMWHs. As the LMWHs are distinct compounds that each possess unique pharmacokinetic and pharmacodynamic profiles, treatment decisions should be based on the available safety and efficacy data for each LMWH. Agents should be prescribed only for those indications for which they have been shown to be effective and only at dosages that have been studied.
Topics: Dalteparin; Enoxaparin; Fibrinolytic Agents; Half-Life; Heparin, Low-Molecular-Weight; Humans; Molecular Structure; Thrombosis; Tinzaparin
PubMed: 11401195
DOI: 10.1592/phco.21.8.62s.34594 -
Thrombosis and Haemostasis Oct 2017Currently, low molecular weight heparin (LMWH) is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is... (Randomized Controlled Trial)
Randomized Controlled Trial
Currently, low molecular weight heparin (LMWH) is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, there are limited data supporting its use in cancer patients. The rationale and design of this investigator initiated Phase IV, multicenter, randomized, open label, superiority trial assessing the safety of apixaban versus dalteparin for cancer associated VTE is provided (ADAM-VTE; NCT02585713). The main aim of the ADAM-VTE trial is to test the hypothesis that apixaban is associated with a significantly lower rate of major bleeding compared to dalteparin in the treatment of cancer patients with acute VTE. The primary safety outcome is rate of major bleeding. Secondary efficacy objective is to assess the rates of recurrent VTE or arterial thromboembolism. Cancer patients with acute VTE (n=300) are randomized to receive apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily thereafter) or dalteparin (200 IU/Kg daily for 30 days followed by 150 IU/kg daily thereafter) for 6 months. Stratification factors used for randomization include cancer stage and cancer specific risk of venous thromboembolism using the Khorana score. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium comprised of 90 oncology practices in the United States and Canada. Based on the hypothesis to be tested, we anticipate that these trial results will provide evidence supporting apixaban as an effective treatment of cancer associated VTE at lower rates of major bleeding compared to LMWH.
Topics: Anticoagulants; Canada; Dalteparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Neoplasms; Pyrazoles; Pyridones; Recurrence; Risk Factors; Time Factors; Treatment Outcome; United States; Venous Thromboembolism
PubMed: 28837207
DOI: 10.1160/TH17-03-0193 -
Lancet (London, England) Feb 2015
Topics: Dalteparin; Female; Fibrinolytic Agents; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombophilia
PubMed: 25706216
DOI: 10.1016/S0140-6736(15)60287-2 -
Journal of Obstetrics and Gynaecology :... May 2019A systematic review of studies published between 1 January 1985 and 31 August 2017 was performed to analyse the efficacy of the low-molecular-weight heparin, dalteparin,...
A systematic review of studies published between 1 January 1985 and 31 August 2017 was performed to analyse the efficacy of the low-molecular-weight heparin, dalteparin, in venous thromboembolism (VTE) treatment and prophylaxis during pregnancy, and to evaluate dosing practices, anticoagulant monitoring and adverse events. A therapeutic dosing throughout pregnancy or followed by reduced doses effectively prevented VTE recurrence. Anti-factor Xa activity was the most commonly used method of dose monitoring. The risk of bleeding with dalteparin was generally minor. Major bleeding was observed when a high dose of dalteparin was employed during (or close to) delivery, or postpartum. Other adverse events were minor. Disparity exists in VTE treatment and thromboprophylaxis, with wide variety in the dosing regimens, treatment strategies and monitoring practices employed. Large randomised controlled trials are warranted but due to ethical reasons, and the rarity of VTE-associated obstetric complications, case-control, registry and large observational studies present more likely options.
Topics: Adult; Anticoagulants; Dalteparin; Female; Humans; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Cardiovascular; Treatment Outcome; Venous Thromboembolism
PubMed: 30426808
DOI: 10.1080/01443615.2018.1499713 -
APMIS : Acta Pathologica,... Dec 2010Tumors are angiogenesis dependent and vascular endothelial growth factor-A (VEGF-A), a heparin-binding protein, is a key angiogenic factor. As chemotherapy and...
Tumors are angiogenesis dependent and vascular endothelial growth factor-A (VEGF-A), a heparin-binding protein, is a key angiogenic factor. As chemotherapy and co-treatment with anticoagulant low-molecular-weight heparin (LMWH) are common in cancer patients, we investigated whether angiogenesis in vivo mediated by VEGF-A is modulated by metronomic-type treatment with: (i) the LMWH dalteparin; (ii) low-dosage cytostatic epirubicin; or (iii) a combination of these two drugs. Using the quantitative rat mesentery angiogenesis assay, in which angiogenesis was induced by intraperitoneal injection of very low doses of VEGF, dalteparin sodium (Fragmin(®) ) and epirubicin (Farmorubicin(®) ) were administered separately or in combination by continuous subcutaneous infusion at a constant rate for 14 consecutive days. Dalteparin was administered at 27, 80, or 240 IU/kg/day, i.e., doses that reflect the clinical usage of this drug, while epirubicin was given at the well-tolerated dosage of 0.4 mg/kg/day. While dalteparin significantly stimulated angiogenesis in an inversely dose-dependent manner, epirubicin did not significantly affect angiogenesis. However, concurrent treatment with dalteparin and epirubicin significantly inhibited angiogenesis. The effect of dalteparin is the first demonstration of a proangiogenic effect of any LMWH in vivo. The fact that co-treatment with dalteparin and epirubicin significantly inhibited angiogenesis suggests a complex drug effect.
Topics: Animals; Antibiotics, Antineoplastic; Anticoagulants; Body Weight; Dalteparin; Epirubicin; Immunohistochemistry; Infusions, Subcutaneous; Male; Mesenteric Arteries; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric; Vascular Endothelial Growth Factor A
PubMed: 21091776
DOI: 10.1111/j.1600-0463.2010.02635.x