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American Journal of Health-system... Apr 2003
Clinical Trial
Topics: Adult; Aged; Anticoagulants; Body Weight; Dalteparin; Drug Prescriptions; Factor Xa; Female; Humans; Male; Middle Aged; Obesity; Pharmacy Service, Hospital; United States
PubMed: 12701550
DOI: 10.1093/ajhp/60.7.683 -
Molecules (Basel, Switzerland) Jun 2017A number of low molecular weight heparin (LMWH) products are available for clinical use and although all share a similar mechanism of action, they are classified as...
A number of low molecular weight heparin (LMWH) products are available for clinical use and although all share a similar mechanism of action, they are classified as distinct drugs because of the different depolymerisation processes of the native heparin resulting in substantial pharmacokinetic and pharmacodynamics differences. While enoxaparin has been extensively investigated, little information is available regarding the LMWH dalteparin. The present study is focused on the detailed structural characterization of Fragmin by LC-MS and NMR applied both to the whole drug and to its enzymatic products. For a more in-depth approach, size homogeneous octasaccharide and decasaccharide components together with their fractions endowed with high or no affinity toward antithrombin were also isolated and their structural profiles characterized. The combination of different analytical strategies here described represents a useful tool for the assessment of batch-to-batch structural variability and for comparative evaluation of structural features of biosimilar products.
Topics: Chromatography, Liquid; Dalteparin; Heparin Lyase; Humans; Mass Spectrometry; Nuclear Magnetic Resonance, Biomolecular
PubMed: 28672818
DOI: 10.3390/molecules22071051 -
Journal of Thrombosis and Haemostasis :... May 2012Superficial thrombophlebitis can produce pain and result in a deep vein thrombosis (DVT) if not treated. Conservative therapies including prescription of non-steroidal... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Superficial thrombophlebitis can produce pain and result in a deep vein thrombosis (DVT) if not treated. Conservative therapies including prescription of non-steroidal anti-inflammatory drugs (NSAID) and heat have been standard care. Recently, studies have been published reporting efficacy and safety of low-molecular-weight heparin for the treatment of superficial thrombophlebitis. However, there are few comparative trials to conservative therapy. We studied the effectiveness and safety of treatment with dalteparin compared with ibuprofen in patients with confirmed superficial thrombophlebitis.
METHODS
Consecutive patients were randomized to receive daily dalteparin vs. ibuprofen three times daily for up to 14 days. The primary outcome measure was the incidence of extension of thrombus or new symptomatic venous thromboembolism during the 14-day and 3-month follow-up period. The secondary outcome was a reduction in pain. The outcome measure of safety was the incidence of major and minor bleeding.
RESULTS
Of 302 consecutive patients screened, 72 were enrolled. Four patients receiving ibuprofen compared with no patients receiving dalteparin had thrombus extension at 14 days (P = 0.05), however, there was no difference in thrombus extension at 3 months. Both treatments significantly reduced pain. There were no episodes of major or minor bleeding during the treatment period.
CONCLUSIONS
Dalteparin is superior to the NSAID ibuprofen in preventing extension of superficial thrombophlebitis during the 14-day treatment period with similar relief of pain and no increase in bleeding. However, questions concerning the optimal treatment duration should be explored in future trials.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Dalteparin; Double-Blind Method; Drug Administration Schedule; Female; Fibrinolytic Agents; Hemorrhage; Humans; Ibuprofen; Injections, Subcutaneous; Male; Middle Aged; Oklahoma; Pain; Risk Assessment; Risk Factors; Thrombophlebitis; Time Factors; Treatment Outcome; Venous Thromboembolism; Young Adult
PubMed: 22360152
DOI: 10.1111/j.1538-7836.2012.04669.x -
Plastic and Reconstructive Surgery Apr 2003Unfractionated heparin is often used to prevent thrombosis in microvascular surgery, but a major drawback of heparin therapy is increased bleeding. Low-molecular-weight... (Comparative Study)
Comparative Study
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.
Topics: Animals; Carotid Artery Thrombosis; Dalteparin; Dose-Response Relationship, Drug; Endarterectomy, Carotid; Heparin; Injections, Intravenous; Microsurgery; Postoperative Complications; Postoperative Hemorrhage; Rats; Rats, Sprague-Dawley; Thrombosis; Treatment Outcome
PubMed: 12655212
DOI: 10.1097/01.PRS.0000053549.45063.A1 -
The American Journal of Medicine Feb 2021
Topics: Anti-Inflammatory Agents; Anticoagulants; Dalteparin; Dermatomyositis; Female; Hemorrhage; Humans; Immunoglobulins, Intravenous; Methylprednisolone; Middle Aged; Retroperitoneal Space
PubMed: 32735853
DOI: 10.1016/j.amjmed.2020.06.038 -
Therapeutische Umschau. Revue... 2016
Review
Topics: Adult; Cesarean Section; Dalteparin; Female; Guideline Adherence; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Pulmonary Embolism; Risk Assessment; Venous Thromboembolism
PubMed: 28045359
DOI: 10.1024/0040-5930/a000838 -
The New England Journal of Medicine Oct 2003
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Bias; Dalteparin; Humans; International Normalized Ratio; Secondary Prevention; Thrombocytopenia; Thromboembolism; Venous Thrombosis
PubMed: 14523150
DOI: 10.1056/NEJM200310023491418 -
Clinical and Applied... Apr 2005The objective of this study was to examine the pharmacokinetics of intravenous dalteparin (Fragmin, Pharmacia-Upjohn, Peapack, NJ) and to assess the accuracy of standard... (Clinical Trial)
Clinical Trial
The objective of this study was to examine the pharmacokinetics of intravenous dalteparin (Fragmin, Pharmacia-Upjohn, Peapack, NJ) and to assess the accuracy of standard coagulation-based monitoring techniques as an estimate of drug concentration with which to guide dosing. Knowledge of the kinetic behavior of low-molecular-weight heparins (LMWHs) and the possible utility of coagulation times for monitoring may aid in the development of safe and effective dosing algorithms for percutaneous coronary interventions. Twenty normal volunteers were treated at 2-week intervals with each of three intravenous dalteparin doses. Measurement of anti-IIa, anti-Xa, activated partial thromboplastin time (aPTT), activated clotting time (ACT), and low-range ACT was performed at baseline and at seven additional time points over 8 hours. The half-life of intravenous dalteparin is 77 minutes with slight dose-related variation. The aPTT, LR-ACT, and standard ACT are prolonged after dalteparin administration with the increase closely correlated to anti-Xa activity (aPTT, r = 0.85; LR-ACT, r = 0.79). Classification of anticoagulation intensity range using aPTT or LR-ACT in comparison to anti-Xa activity (0.5-0.99, 1.0-1.49, 1.5-2, >2) displays a level of agreement (kappa: aPTT = 0.69, LR-ACT = 0.59) that is comparable to values reported for coagulation time guidance of unfractionated heparin administration. Standard coagulation times are sensitive to the anticoagulant effect of dalteparin with a degree of correlation that suggests their utility for estimating drug concentration during high dose therapy. Trials establishing a relationship between monitoring and clinical efficacy, and the risk/reward of different treatment ranges alone or in combination with GPIIb/IIIa inhibitors and clopidogrel, are necessary.
Topics: Adult; Blood Coagulation; Blood Coagulation Tests; Calcium; Dalteparin; Drug Monitoring; Factor Xa; Female; Humans; Infusions, Intravenous; Male; Time Factors
PubMed: 15821819
DOI: 10.1177/107602960501100202 -
Journal of Thrombosis and Haemostasis :... Oct 2009Low-molecular-weight heparins (LMWH) are effective, safe and convenient for anticoagulation. Their use is limited in patients with renal insufficiency (RI) because of... (Comparative Study)
Comparative Study
BACKGROUND
Low-molecular-weight heparins (LMWH) are effective, safe and convenient for anticoagulation. Their use is limited in patients with renal insufficiency (RI) because of bioaccumulation.
OBJECTIVES
Evaluate pharmacokinetic data of dalteparin at a therapeutic dose in patients with RI.
PATIENTS AND METHODS
Prospective observational cohort study. Inpatients were included into three groups according to glomerular filtration rate (GFR): A > or = 60, B 30-59, C < 30 mL min(-1) 1.73 m(-2). Dalteparin was injected subcutaneously (s.c.) twice daily. Peak plasma anti-factor Xa activity (anti-Xa) was measured and adjusted to applied dose and body weight after the first dose, on day 2, and every 2nd day afterwards. Bioaccumulation factor R was calculated as quotient of the last and the first adjusted anti-Xa. Data are shown as median (interquartile range, IQR).
RESULTS
Thirty-two patients (23 men) receiving dalteparin for > or = 2 days were analyzed. Follow-up was 6 days (IQR 4-10, range 2-22). Median dose was 90 (73-106) units kg(-1) per 12 h (P = 0.68). After the first dose, adjusted anti-Xa levels were 3.5 (2.6-5.0), 4.8 (3.3-5.5), 4.5 (3.7-7.5) x 10(-3) for the groups A, B, C; P = 0.26. On the last day, they were 6.1 (3.7-7.3), 7.1 (5.6-8.3), 10.2 (7.8-13.2) x 10(-3); A compared with C, P = 0.002. R was 1.46 (1.15-1.82), 1.36 (1.20-2.16) and 2.28 (1.53-2.93); A compared with C, P = 0.18.
CONCLUSION
Therapeutically dosed dalteparin accumulates in patients with severe RI (group C). Dose adjustments according to anti-Xa are recommended for dalteparin if used in this patient population. However, no simple dosing scheme can be suggested yet because of wide inter-individual variation.
Topics: Aged; Aged, 80 and over; Anticoagulants; Dalteparin; Factor Xa Inhibitors; Female; Glomerular Filtration Rate; Humans; Injections, Subcutaneous; Inpatients; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Prospective Studies
PubMed: 19624460
DOI: 10.1111/j.1538-7836.2009.03556.x -
Canadian Journal of Anaesthesia =... Nov 2019
Topics: Anticoagulants; Dalteparin; Extracorporeal Circulation; Humans; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 31396861
DOI: 10.1007/s12630-019-01460-2