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Journal of Cancer Research and... Dec 2018To investigate the effects of dalteparin sodium on the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and hypoxia-inducible factor 1α...
PURPOSE
To investigate the effects of dalteparin sodium on the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and hypoxia-inducible factor 1α (HIF-1α) in A549 human lung cancer (LC) cell line and a human A549-grafted nude mouse model.
MATERIALS AND METHODS
A549 human lung adenocarcinoma cell line was divided into control group, treated using normal saline (NS); and dalteparin sodium groups, receiving 5, 15, 50, and 150 IU/ml of dalteparin sodium, respectively. Human A549-grafted nude mouse was induced through subcutaneous (SC) injection of A549 (5 × 10/0.2 ml) into the right armpit, and randomly assigned into control group (n = 6) receiving intraperitoneal (i.p.) injection of NS, cisplatin (DDP) group (n = 6, 3 mg/kg DDP alone, i.p., for 3 days), low molecular weight heparin (LMWH) group (n = 6) receiving SC injection of 1500 IU/kg dalteparin sodium for 35 days, and DDP plus LMWH group (n = 6, 3 mg/kg DDP, i.p., for 3 days, followed by SC injection of 1500 IU/kg dalteparin sodium for 35 days).
RESULTS
Significant difference was noted in the messenger RNA expression of VEGF, VEGFR, and HIF-1α after treating with heparin with a concentration of 15, 50, or 150 IU/ml in the A549 cell line at 24 and 48 h, respectively. In the human A549-grafted nude mouse model, a significant reduction was noted in the expression of VEGF, VEGFR, and HIF-1α in the tumor mass harvested from the mice receiving administration of dalteparin sodium plus DDP.
CONCLUSION
Dalteparin sodium had the inhibitory effects on the growth of human LC A549 cells in vitro and A549 LC xenograft model, which could be enhanced when administrated together with DDP.
Topics: A549 Cells; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Cisplatin; Dalteparin; Drug Synergism; Female; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Receptors, Vascular Endothelial Growth Factor; Treatment Outcome; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays
PubMed: 30539834
DOI: 10.4103/0973-1482.192765 -
Journal of Thrombosis and Haemostasis :... Oct 2010
Topics: Adult; Anticoagulants; Calibration; Creatinine; Dalteparin; Drug Overdose; Female; Heparin; Humans; Partial Thromboplastin Time; Prothrombin Time; Risk; Suicide, Attempted; Thromboembolism; Time Factors
PubMed: 20629941
DOI: 10.1111/j.1538-7836.2010.03984.x -
Annals of Oncology : Official Journal... Feb 2006Cancer patients receiving chemotherapy experience thromboembolic complications associated with the use of long-term indwelling central venous catheters (CVCs). This... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: final results of a double-blind, placebo-controlled phase III trial.
BACKGROUND
Cancer patients receiving chemotherapy experience thromboembolic complications associated with the use of long-term indwelling central venous catheters (CVCs). This prospective, double-blind, placebo-controlled, multicenter study evaluated whether prophylactic treatment with a low molecular weight heparin could prevent clinically relevant catheter-related thrombosis.
PATIENTS AND METHODS
Patients with cancer undergoing chemotherapy for at least 12 weeks (n=439) were randomly assigned, in a 2:1 ratio, to receive either dalteparin (5000 IU) or placebo, by subcutaneous injection, once daily for 16 weeks. Patients underwent upper extremity evaluation with either venography or ultrasound at the time of a suspected catheter-related complication (CRC) or upon completion of study medication. The primary end point, as determined by a blinded adjudication committee, was the occurrence of a CRC, defined as the first occurrence of any one of the following: clinically relevant catheter-related thrombosis that was symptomatic or that required anticoagulant or fibrinolytic therapy; catheter-related clinically relevant pulmonary embolism; or catheter obstruction requiring catheter removal.
RESULTS
There was no significant difference in the frequency of CRCs between the dalteparin arm (3.7%) and the placebo arm (3.4%; P=0.88), corresponding to a relative risk of 1.0883 (95% confidence interval 0.37-3.19). No difference in the time to CRC was observed between the two arms (P=0.83). There was no significant difference between the dalteparin and placebo groups in terms of major bleeding (1 versus 0) or overall safety.
CONCLUSIONS
Dalteparin prophylaxis did not reduce the frequency of thromboembolic complications after CVC implantation in cancer patients. Dalteparin was demonstrated to be safe over 16 weeks of treatment in these patients.
Topics: Anticoagulants; Antineoplastic Agents; Catheterization, Central Venous; Catheters, Indwelling; Dalteparin; Female; Humans; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Risk Factors; Thromboembolism
PubMed: 16317012
DOI: 10.1093/annonc/mdj059 -
Thrombosis Research Nov 2015This study focused on the clinical outcomes in multiple myeloma (MM) patients with venous thromboembolism (VTE) who received low-molecular-weight heparin (dalteparin)...
This study focused on the clinical outcomes in multiple myeloma (MM) patients with venous thromboembolism (VTE) who received low-molecular-weight heparin (dalteparin) therapy. Changes in D-dimer levels before and after VTE were also evaluated. Among 549 patients treated with various chemotherapeutic agents, a total of 52 (9.47%) patients including 32 newly diagnosed with MM and 16 with relapsed/refractory MM developed VTE, 48 of whom received dalteparin. Among the 48 treated patients, 37 (77%) had proximal deep vein thrombosis (DVT), four had (8%) pulmonary embolism (PE), and seven (15%) had both DVT and PE. In 32 patients with available paired samples (at baseline and VTE occurrence), significant conversion of D-dimer levels from 2.2 ± 0.4 mg/L to 11.8 ± 1.6 mg/L (P < 0.001) was observed, which decreased from 10.9 ± 0.4 mg/L to 1.9 ± 0.6 mg/L one month after initiating dalteparin therapy. A total of 44 patients received dalteparin with a median duration of 4.2 months (range, 2.7-9.4), and four patients were discontinued early due to death (n = 3) and major bleeding (n = 1). After a median follow-up of 9.0 months (range, 0.7-35.8) since the first VTE episode, five patients showed recurrence of VTE with a cumulative incidence of 17.5 ± 7.9%. Major bleeding occurred in three patients. In summary, dalteparin seems to be a promising drug for the treatment of VTE in MM. In addition, the significant difference in D-dimer levels observed before occurrence of VTE and after dalteparin treatment may suggest the usefulness of D-dimer testing as a surrogate marker for VTE in MM patients.
Topics: Adult; Aged; Dalteparin; Female; Humans; Incidence; Male; Middle Aged; Multiple Myeloma; Risk Factors; Treatment Outcome; Venous Thromboembolism
PubMed: 26432650
DOI: 10.1016/j.thromres.2015.09.021 -
Angiologiia I Sosudistaia Khirurgiia =... 2011The article contains a review of the literature regarding the use of low-molecular-weight heparins (LMWHs) exemplified by dalteparin in the hitherto insufficiently... (Review)
Review
The article contains a review of the literature regarding the use of low-molecular-weight heparins (LMWHs) exemplified by dalteparin in the hitherto insufficiently explored area of their implementation, i. e., during the intraoperative period in patients suff ering from atherothrombosis. Presented herein is analysis of alterations in the parameters of the plasmatic and thrombocytic links of haemostatis during intraoperative administration of various molecular-weight fractions of heparin. The obtained findings make it possible to conclude that LMWHs do off er certain advantages when used during surgical interventions in patients with atherosclerotic lesions of the arterial bed.
Topics: Anticoagulants; Arterial Occlusive Diseases; Arteries; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Clinical Trials as Topic; Dalteparin; Drug Monitoring; Hemostasis, Surgical; Heparin; Humans; Intraoperative Complications; Patient Selection; Risk Assessment; Thrombosis; Vascular Surgical Procedures
PubMed: 21983457
DOI: No ID Found -
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 -
European Heart Journal. Cardiovascular... Oct 2019
Topics: Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Dalteparin; Factor Xa Inhibitors; Humans; Neoplasms; Pyridines; Recurrence; Risk Factors; Secondary Prevention; Thiazoles; Treatment Outcome; Venous Thromboembolism
PubMed: 31378809
DOI: 10.1093/ehjcvp/pvz027 -
Heart Disease (Hagerstown, Md.) 1999Acute coronary syndromes account for tens of thousands of emergency room visits and cost the United States healthcare system billions of dollars each year. Dalteparin is...
Acute coronary syndromes account for tens of thousands of emergency room visits and cost the United States healthcare system billions of dollars each year. Dalteparin is a low molecular weight heparin (LMWH) recently approved for treatment of unstable angina and non-Q wave myocardial infarction (NQWMI). The LMWHs possess distinct advantages over unfractionated heparin (UFH). Some of these advantages include administration by subcutaneous injection with no intravenous access required; laboratory monitoring of activated partial thromboplastin time (aPTT) is not required; improved side effect profile; and more predictable and consistent anticoagulant response. In conjunction with aspirin, dalteparin was evaluated for the treatment of unstable angina and NQWMI in three large clinical trials. The FRISC study established the value of short-term dalteparin in patients with unstable coronary artery disease, but suggested that treatment with 120 IU/kg subcutaneously twice daily may be required for more than 6 days. The FRIC trial determined there was no difference between dalteparin and UFH in the acute setting for prevention of death or myocardial infarction (MI). Similar to the FRISC trial, the FRIC trial failed to demonstrate a benefit of dalteparin beyond the acute phase. The FRISC II study demonstrated a significant decrease in the composite endpoint of death or MI in the dalteparin group at 30 days, but not at 3 or 6 months. The early protective effects of dalteparin could be used to lower the risk of events in patients waiting for invasive procedures.
Topics: Angina Pectoris; Anticoagulants; Dalteparin; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Syndrome
PubMed: 11720639
DOI: No ID Found -
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 -
Clinical and Experimental Pharmacology... Nov 20111. The low molecular weight heparin (LMWH) dalteparin is used, for example, to prevent primary venous thromboembolism in patients undergoing surgery or in medically ill...
1. The low molecular weight heparin (LMWH) dalteparin is used, for example, to prevent primary venous thromboembolism in patients undergoing surgery or in medically ill patients. The anticoagulant activity of dalteparin can be monitored by measuring anti-factor Xa levels and activated partial thromboplastin time (aPTT); however, aPTT is an unreliable parameter in this case. The aim of the present in vitro study was to evaluate the thrombelastograph ROTEM(®) (Tem International, Munich, Germany) with respect to determining the anticoagulant activity of dalteparin at therapeutic and supratherapeutic plasma concentrations. 2. The ROTEM(®) parameters, namely coagulation time (CT), clot formation time (CFT) and maximum clot firmness (MCF), were measured using the reagents EXTEM and INTEM (Pentapharm, Munich, Germany) at increasing concentrations of dalteparin (0.01-10 μg/mL, which corresponded to anti-factor Xa levels of 1-1000 U/mL, respectively). 3. The mean CT measured using EXTEM was found to increase from 65.4 ± 27.9 s at baseline to 173.3 ± 112.2 s and 332.2 ± 200.7 s at drug concentrations of 1 and 10 μg/mL, respectively (P < 0.0001 for both). Moreover, the mean CFT value (EXTEM) increased from 97.7 ± 21.5 s at baseline to 187.6 ± 115.2 s (P = 0.0001) at a drug concentration of 10 μg/mL, which is greater than the therapeutic anti-factor Xa concentrations for LMWH. The results obtained when INTEM was used as the reagent were similar to those obtained using EXTEM. 4. In conclusion, the results indicate that the thrombelastograph ROTEM(®) can detect the anticoagulant effects of dalteparin only at supratherapeutic levels of anti-factor Xa.
Topics: Adult; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Dalteparin; Dose-Response Relationship, Drug; Factor Xa; Factor Xa Inhibitors; Germany; Heparin, Low-Molecular-Weight; Humans; Male; Partial Thromboplastin Time; Thrombelastography
PubMed: 21883380
DOI: 10.1111/j.1440-1681.2011.05593.x