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American Journal of Veterinary Research Oct 2012To evaluate the pharmacodynamic effects of dalteparin in dogs by means of viscoelastic coagulation monitoring with a thromboelastograph and a dynamic viscoelastic...
OBJECTIVE
To evaluate the pharmacodynamic effects of dalteparin in dogs by means of viscoelastic coagulation monitoring with a thromboelastograph and a dynamic viscoelastic coagulometer.
ANIMALS
6 healthy adult mixed-breed dogs.
PROCEDURES
Dalteparin (175 U/kg, SC, q 12 h) was administered for 4 days (days 1 through 4). Viscoelastic coagulation monitoring was performed hourly on the first and last days of treatment and included intermittent measurement of anti-activated coagulation factor X activity (AXA).
RESULTS
Dalteparin administration resulted in progressive hypocoagulability. On both day 1 and 4, activated clotting time and clot rate for the dynamic viscoelastic coagulometer differed significantly from baseline values, whereas the platelet function parameter did not change on day 1 but did on day 4. The R (reaction time), time from reaction time until the amplitude of the thromboelastography tracing is 20 mm, α-angle, and maximum amplitude differed from baseline values on days 1 and 4, although many thromboelastographic variables were not determined. The AXA was increased from baseline values at 3 and 6 hours after administration of the dalteparin injection on days 1 and 4, and all dogs had AXA values between 0.5 and 1.0 U/mL at 2 and 4 hours after administration. The AXA correlated well with activated clotting time (r = 0.761) and with R (r = 0.810), when values were available. Thromboelastography could not be used to distinguish AXA > 0.7 U/mL.
CONCLUSIONS AND CLINICAL RELEVANCE
Viscoelastic coagulation monitoring with strong coagulation activators may be used to monitor treatment with dalteparin in healthy dogs.
Topics: Animals; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Dalteparin; Dogs; Dose-Response Relationship, Drug; Factor X; Female; Injections; Male; Thrombelastography
PubMed: 23013183
DOI: 10.2460/ajvr.73.10.1577 -
Archives of Internal Medicine Mar 2001
Comparative Study
Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Dalteparin; Humans; Treatment Outcome; Venous Thrombosis; Warfarin
PubMed: 11231726
DOI: 10.1001/archinte.161.5.776 -
BioMed Research International 2014Drug repositioning is one of the most rapidly emerging fields of study. This concept is anchored on the principle that diseases have similar damaged or affected... (Review)
Review
Drug repositioning is one of the most rapidly emerging fields of study. This concept is anchored on the principle that diseases have similar damaged or affected signaling pathways. Recently, drugs have been repositioned not only for their alternative therapeutic uses but also for their applications as biomaterials in various fields. However, medical drugs as biomaterials are rarely focused on in reviews. Fragmin and protamine have been recently the sources of increasing attention in the field of tissue engineering and regenerative medicine. Fragmin and protamine have been manufactured primarily as a safe antidote for the circulating heparin. Lately, these drugs have been utilized as either micro- or nanoparticle biomaterials. In this paper, we will briefly describe the concept of drug repositioning and some of the medical drugs that have been repurposed for their alternative therapeutic uses. Also, this will feature the historical background of the studies focused on fragmin/protamine micro/nanoparticles (F/P M/NPs) and their applications as biomaterials in tissue engineering, stem cell therapy, and regenerative medicine.
Topics: Cell- and Tissue-Based Therapy; Dalteparin; Drug Repositioning; Heparin; Humans; Nanoparticles; Protamines; Regenerative Medicine; Signal Transduction; Stem Cells; Tissue Engineering
PubMed: 24995338
DOI: 10.1155/2014/936196 -
Archives of Iranian Medicine Jul 2008Retinal vein occlusion is the second most common vascular disease of retina after diabetic retinopathy, affecting 1.6% of the population above the age of 40. The aim of... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Retinal vein occlusion is the second most common vascular disease of retina after diabetic retinopathy, affecting 1.6% of the population above the age of 40. The aim of this study was to compare the effect of dalteparin and aspirin in patients with recent-onset branch retinal vein occlusion.
METHODS
A randomized clinical trial was conducted on patients with branch retinal vein occlusion of less than 30 days' duration. Ophthalmic, systemic, and hematologic evaluations were made. Visual acuity was measured with Early Treatment Diabetic Retinopathy Study chart. Patients in the dalteparin group received subcutaneous dalteparin 100 IU/kg twice daily for 10 days, then 100 IU/kg once daily for another 10 days while the patients in the aspirin group were given aspirin 100 mg daily throughout the study.
RESULTS
Seventy-eight patients were enrolled, 37 in the dalteparin and 41 in the aspirin group. The patients were followed for six months. The visual outcomes of the two groups were compared. Although dalteparin improved mean visual acuity slightly more than aspirin, no statistically significant differences were found between the groups at one (P=0.37), two (P=0.16), three (P=0.11), or six (P=0.13) months. Resolution of macular edema and development of new vessels made no statistically significant difference between the groups [(P=0.08) and (P=0.49), respectively].
CONCLUSION
In recent-onset branch retinal vein occlusion, no significant difference was found in the final visual acuity between the patients treated by dalteparin or aspirin. A further study with larger sample size is recommended.
Topics: Aspirin; Dalteparin; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Retinal Vein Occlusion; Time Factors
PubMed: 18588374
DOI: No ID Found -
Journal of Thrombosis and Thrombolysis Jan 2020Cancer increases risk for venous thromboembolism. Incident thrombocytopenia increases hemorrhagic risk. Hospitalized adults with a cancer diagnosis who received... (Observational Study)
Observational Study
Cancer increases risk for venous thromboembolism. Incident thrombocytopenia increases hemorrhagic risk. Hospitalized adults with a cancer diagnosis who received subcutaneous dalteparin in doses adjusted according to platelet count were retrospectively evaluated. Outcomes of interest included nadir platelet counts, transfusions, thromboembolism, and hemorrhage. During a 2-year period of observation, 1854 cancer patients received individualized inpatient treatment with dalteparin. Transfusion was required in 38 of 77 (49.4%) patients with nadir platelet counts < 25 × 10 cells/L as compared with 16 of 75 (21.3%) patients whose nadir platelet counts were 25-50 × 10 cells/L [risk ratio (RR) 2.31; 95% CI 1.42 to 3.78, p < 0.001] and 45 of 1657 (2.7%) patients with platelet counts > 50 × 10 cells/L (RR - 8.07; 95% CI - 4.79 to - 13.59, p < 0.001). Transfusions were administered primarily as supportive therapy. Among transfusion recipients, new or recurrent venous thromboembolism was documented in 2.6%, 0%, and 2.2% of patients with nadir platelet counts of < 25, 25-50, or > 50 × 10 cells/L, respectively (p > 0.9 for all comparisons). Acute blood loss or major bleeding was documented in 10.5%, 12.5%, and 15.6% of patients with platelet counts of < 25, 25-50, or > 50 × 10 cells/L, respectively (p > 0.9 for all comparisons). Among hospitalized cancer patients who received individualized dalteparin treatment, transfusion requirements varied inversely with platelet count. Irrespective of platelet counts, occurrence rates for venous thromboembolism and acute hemorrhage were similar across all treatment groups. Individualized dalteparin treatment provided a consistent pattern of safety and effectiveness.
Topics: Adult; Aged; Blood Transfusion; Dalteparin; Female; Hospitalization; Humans; Incidence; Male; Middle Aged; Neoplasms; Platelet Count; Thrombocytopenia; Thromboembolism
PubMed: 31468319
DOI: 10.1007/s11239-019-01935-5 -
Haematologica Jul 2022The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism... (Randomized Controlled Trial)
Randomized Controlled Trial
Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial.
The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We ran a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as a risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancerassociated VTE. RI was graded as moderate (creatinine clearance between 30-59 mL/minute; 275 patients) and mild (between 60- 89 mL/minute; 444 patients). In the 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06-95% CI: 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR=0.67, 95% CI: 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR=0.27, 95% CI: 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR=2.84, 95% CI: 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study, in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin. ClinicalTrials.gov identifier: NCT03045406.
Topics: Anticoagulants; Dalteparin; Hemorrhage; Humans; Kidney; Neoplasms; Pyrazoles; Pyridones; Venous Thromboembolism
PubMed: 34382385
DOI: 10.3324/haematol.2021.279072 -
The Annals of Pharmacotherapy Apr 2008The low-molecular-weight heparin (LMWH) dalteparin is approved by the Food and Drug Administration for prophylaxis of venous thromboembolism (VTE) in adults and has...
BACKGROUND
The low-molecular-weight heparin (LMWH) dalteparin is approved by the Food and Drug Administration for prophylaxis of venous thromboembolism (VTE) in adults and has recently received an indication for acute VTE therapy in adults with cancer. Published reports of experience with dalteparin use in European children suggest that this LMWH agent is safe and effective in the prophylaxis and treatment of VTE in the pediatric population. However, dalteparin is commonly available in the US in a concentrated form that requires dilution for accurate administration in infants and young children.
OBJECTIVE
To investigate the in vitro stability of diluted dalteparin for pediatric use, as measured by serial anti-Xa activity assays over the course of 4 weeks.
METHODS
At 2 clinical research pharmacies, dalteparin multidose vials (anti-Xa concentration 25,000 U/mL) of the 2 distinct lots presently available for clinical use were diluted 1:10 with preservative-free NaCl 0.9% and maintained in tuberculin syringes at 4 degrees C. Syringes were then sampled for anti-Xa activity by chromogenic assay at baseline and weekly over the course of 4 weeks.
RESULTS
For each lot of dalteparin, there was strong agreement in anti-Xa activity between corresponding diluted syringes prepared at the 2 pharmacy sites. No statistically significant difference in anti-Xa activity was detected from baseline to any time point, nor was a trend of change detected in anti-Xa activity with time for either lot of dalteparin.
CONCLUSIONS
These data indicate that the anti-Xa activity of diluted dalteparin for pediatric use is stable over the course of 4 weeks.
Topics: Anticoagulants; Dalteparin; Drug Stability; Drug Storage; Factor Xa; Factor Xa Inhibitors; Glass; Humans; Injections, Intravenous; Pediatrics; Pharmaceutical Solutions; Syringes; Temperature; Time Factors
PubMed: 18349310
DOI: 10.1345/aph.1K609 -
Hip International : the Journal of... 2010Chemical thromboprophylaxis in total hip arthroplasty (THA) may increase surgical site bleeding. The drug dose and timing of such therapy is therefore important. We...
Chemical thromboprophylaxis in total hip arthroplasty (THA) may increase surgical site bleeding. The drug dose and timing of such therapy is therefore important. We studied two cohorts of 298 and 301 patients undergoing THA. The first group received their first dose of dalteparin sodium 5000 IU subcutaneously the evening before surgery and the second group a half dose six hours postoperatively, followed by 5000 units daily in both groups. Blood loss was reduced by 146 ml from 1230 ml to 1084 ml (p<0.001) with postoperative prophylaxis alone. The number of patients receiving blood transfusion decreased from 53% to 35% (p=0.001), and the use of transfused packed red blood cells was reduced from 1.25 to 0.83 units per patient (p=0.001). The overall rates of non-vascular complications 6 months after surgery were 12% and 11%, bleeding related events 6.0% and 4.0%, and thromboembolic related events were 2.0% and 2.3% in the preoperative and the postoperative cohorts. Two patients died in the preoperative group and one in the postoperative group due to venous and arterial thromboembolism. This study show that 2500 IU dose of dalteparin started 6 hours after surgery significantly reduced blood loss and transfusions compared to 5000 IU dalteparin injected 12 hours before surgery. Few thromboembolic events occurred, and these were equally distributed.
Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Blood Loss, Surgical; Blood Transfusion; Cohort Studies; Dalteparin; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Norway; Postoperative Care; Premedication; Preoperative Care; Thrombophlebitis
PubMed: 20640994
DOI: 10.1177/112070001002000302 -
Journal of Gynecologic Oncology Jan 2020Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous... (Comparative Study)
Comparative Study
OBJECTIVES
Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous thromboembolism (VTE) have previously been performed. However, gynecologic cancers accounted for approximately 10% of the study populations. We compared the outcomes of patients with primary gynecological cancers who were treated for cancer-associated VTE with either rivaroxaban or dalteparin.
METHODS
The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality.
RESULTS
During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%).
CONCLUSION
In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.
Topics: Aged; Dalteparin; Factor Xa Inhibitors; Female; Genital Neoplasms, Female; Hemorrhage; Humans; Middle Aged; Proportional Hazards Models; Republic of Korea; Rivaroxaban; Venous Thromboembolism
PubMed: 31789000
DOI: 10.3802/jgo.2020.31.e10 -
Archives of Internal Medicine Feb 2005We 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...
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.
Topics: Aged; Aged, 80 and over; Anticoagulants; Dalteparin; Female; Humans; Logistic Models; Male; Multivariate Analysis; Obesity; Retrospective Studies; Risk; Safety; Thromboembolism; Venous Thrombosis
PubMed: 15710801
DOI: 10.1001/archinte.165.3.341