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Population Pharmacokinetic Analysis of Dalteparin in Pediatric Patients With Venous Thromboembolism.Journal of Clinical Pharmacology Feb 2021This article describes the population pharmacokinetics (PK) of dalteparin in pediatric patients with venous thromboembolism (VTE). A prospective multicenter open-label...
This article describes the population pharmacokinetics (PK) of dalteparin in pediatric patients with venous thromboembolism (VTE). A prospective multicenter open-label study was conducted in children who required anticoagulation for the treatment of VTE. The study population included children with and without cancer. The goal was to describe the pharmacokinetics of dalteparin using anti-Xa as a surrogate marker and to determine the dose required to achieve therapeutic anti-Xa levels (0.5-1.0 IU/mL). The anti-Xa data were supplemented with 2 published studies and analyzed using population pharmacokinetic approaches. The pharmacokinetics of dalteparin following subcutaneous injection in pediatric patients was described by a 1-compartment model with linear absorption and elimination. Body weight was added as a covariate on both CL/F and Vd/F as a power function with fixed exponents of 0.75 and 1.0, respectively. The estimates of CL/F and Vd/F in the full model were 929 mL/h and 7180 mL, respectively, for a reference female patient aged 12 years with body weight of 43 kg. Body weight-normalized CL/F decreased with age. Cancer status and sex did not have significant effects on CL/F and Vd/F. Simulations were conducted to select starting doses of dalteparin that would rapidly achieve therapeutic anti-Xa levels. These simulations suggested that the recommended starting doses of dalteparin administered subcutaneously in pediatric patients of different age cohort groups for treatment of VTE were 150 IU/kg every 12 hours (1 month to <2 years), 125 IU/kg every 12 hours (≥2 to <8 years), and 100 IU/kg every 12 hours (≥8 to <19 years).
Topics: Adolescent; Age Factors; Anticoagulants; Biomarkers; Body Weight; Child; Child, Preschool; Dalteparin; Factor Xa Inhibitors; Female; Humans; Infant; Infant, Newborn; Injections, Subcutaneous; Male; Metabolic Clearance Rate; Prospective Studies; Sex Factors; Venous Thromboembolism
PubMed: 32827160
DOI: 10.1002/jcph.1716 -
International Journal of Obstetric... Dec 2016Dalteparin is often used for prophylaxis or treatment of venous thromboembolism during pregnancy, yet there is no laboratory test to accurately reflect its clinical...
BACKGROUND
Dalteparin is often used for prophylaxis or treatment of venous thromboembolism during pregnancy, yet there is no laboratory test to accurately reflect its clinical activity. Thromboelastography is a point-of-care monitor of whole blood coagulation. The aim of this study was to determine if serial doses of dalteparin added in vitro to whole blood samples from term, pregnant women are detectable as changes in thromboelastography parameters.
METHODS
Thirty healthy parturients presenting for elective caesarean section were recruited. Dalteparin was added to whole blood samples to yield final concentrations of 0 (control), 0.05, 0.25, 0.5, 0.75 and 1.0U/mL anti-Xa activity. Thromboelastography tracings were obtained for all six samples using the standard kaolin protocol.
RESULTS
Significant differences were noted in median thromboelastography r time, k time, alpha angle and maximal amplitude between non-anticoagulated (⩽0.05U/mL) and samples ⩾0.5U/mL (P<0.05). The r time and k time presented with the highest sensitivities of 97.5 and 84.0, respectively.
CONCLUSION
This pilot study provides proof-of-concept that thromboelastography can discriminate differences in blood anticoagulated with varying doses of dalteparin in a dose-dependent manner. This suggests that thromboelastography may be a feasible monitor of anticoagulation in the presence of dalteparin in maternal whole blood and may potentially translate to a point-of-care test that can be used to determine real-time coagulation status in patients.
Topics: Adolescent; Adult; Anticoagulants; Dalteparin; Female; Humans; In Vitro Techniques; Middle Aged; Pilot Projects; Pregnancy; Thrombelastography; Young Adult
PubMed: 27717636
DOI: 10.1016/j.ijoa.2016.08.002 -
Journal of the College of Physicians... Mar 2021To determine the effect and safety of sequential treatment with the low-molecular-weight heparin dalteparin and the direct oral anticoagulants rivaroxaban in patients... (Observational Study)
Observational Study
OBJECTIVE
To determine the effect and safety of sequential treatment with the low-molecular-weight heparin dalteparin and the direct oral anticoagulants rivaroxaban in patients with cancer- associated venous thromboembolism (VTE).
STUDY DESIGN
Observational study.
PLACE AND DURATION OF STUDY
Department of Oncology, the Second Affiliated Hospital of Soochow University, between January 2017 and September 2019.
METHODOLOGY
Patients with active cancer, diagnosed with VTE and who received sequential treatment with dalteparin and rivaroxaban, were retrospectively reviewed. Logistic regression analysis was used to identify risk factors associated with VTE recurrence.
RESULTS
Ninety-nine patients with active cancer were enrolled in the study. The median delteparin treatment time was nine days (5-20 days), and 2.8 months (1-6 months) for rivaroxaban. Sixty (60.6%) patients had eliminated VTE, and 39 (39.4%) had persistent VTE, but with relieved symptoms. No major bleeding was observed. Eleven (11.1%) patients had minor bleeding, including melena (5.1%), hematuria (3.0%), vaginal bleeding (1.0%), gingival bleeding (1.0%), and subcutaneous hemorrhage (1.0%). During the 6 months follow-up period, one (1.0%) developed pulmonary embolism, and seven (7.1%) experienced recurrent VTE. Univariate logistic regression analysis showed that bleeding occurrence and anticoagulant treatment duration were the two significant factors affecting VTE recurrence (p<0.05).
CONCLUSION
Maintenance of rivaroxaban after initial dalteparin treatment could effectively reduce the risk of VTE recurrence and was well tolerated by patients with cancer-associated VTE. However, in the clinical practice, the treatment duration is often insufficient, so it is essential to follow-up these patients to ensure sufficient treatment time. Key Words: Venous thromboembolism, Low-molecular-weight heparins, Directly oral anticoagulants, Cancer.
Topics: Anticoagulants; Dalteparin; Female; Humans; Neoplasms; Retrospective Studies; Rivaroxaban; Venous Thromboembolism
PubMed: 33775018
DOI: 10.29271/jcpsp.2021.03.294 -
Canadian Journal of Surgery. Journal... Feb 2010
Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Dalteparin; Humans; Postoperative Complications; Thromboembolism
PubMed: 20100404
DOI: No ID Found -
The New England Journal of Medicine Apr 2011The effects of thromboprophylaxis with low-molecular-weight heparin, as compared with unfractionated heparin, on venous thromboembolism, bleeding, and other outcomes are... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The effects of thromboprophylaxis with low-molecular-weight heparin, as compared with unfractionated heparin, on venous thromboembolism, bleeding, and other outcomes are uncertain in critically ill patients.
METHODS
In this multicenter trial, we tested the superiority of dalteparin over unfractionated heparin by randomly assigning 3764 patients to receive either subcutaneous dalteparin (at a dose of 5000 IU once daily) plus placebo once daily (for parallel-group twice-daily injections) or unfractionated heparin (at a dose of 5000 IU twice daily) while they were in the intensive care unit. The primary outcome, proximal leg deep-vein thrombosis, was diagnosed on compression ultrasonography performed within 2 days after admission, twice weekly, and as clinically indicated. Additional testing for venous thromboembolism was performed as clinically indicated. Data were analyzed according to the intention-to-treat principle.
RESULTS
There was no significant between-group difference in the rate of proximal leg deep-vein thrombosis, which occurred in 96 of 1873 patients (5.1%) receiving dalteparin versus 109 of 1873 patients (5.8%) receiving unfractionated heparin (hazard ratio in the dalteparin group, 0.92; 95% confidence interval [CI], 0.68 to 1.23; P=0.57). The proportion of patients with pulmonary emboli was significantly lower with dalteparin (24 patients, 1.3%) than with unfractionated heparin (43 patients, 2.3%) (hazard ratio, 0.51; 95% CI, 0.30 to 0.88; P=0.01). There was no significant between-group difference in the rates of major bleeding (hazard ratio, 1.00; 95% CI, 0.75 to 1.34; P=0.98) or death in the hospital (hazard ratio, 0.92; 95% CI, 0.80 to 1.05; P=0.21). In prespecified per-protocol analyses, the results were similar to those of the main analyses, but fewer patients receiving dalteparin had heparin-induced thrombocytopenia (hazard ratio, 0.27; 95% CI, 0.08 to 0.98; P=0.046).
CONCLUSIONS
Among critically ill patients, dalteparin was not superior to unfractionated heparin in decreasing the incidence of proximal deep-vein thrombosis. (Funded by the Canadian Institutes of Health Research and others; PROTECT ClinicalTrials.gov number, NCT00182143.).
Topics: Anticoagulants; Critical Illness; Dalteparin; Female; Hemorrhage; Heparin; Humans; Incidence; Injections, Subcutaneous; Kaplan-Meier Estimate; Male; Middle Aged; Pulmonary Embolism; Thrombocytopenia; Thromboembolism; Venous Thrombosis
PubMed: 21417952
DOI: 10.1056/NEJMoa1014475 -
The New England Journal of Medicine Jul 2003Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer.
METHODS
Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months).
RESULTS
During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group.
CONCLUSIONS
In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Dalteparin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Secondary Prevention; Survival Analysis; Thromboembolism; Venous Thrombosis; Warfarin
PubMed: 12853587
DOI: 10.1056/NEJMoa025313 -
Angiology Sep 2023Women with a history of venous thromboembolisms (VTEs) and/or thrombophilia are at increased risk of VTE during pregnancy. We analysed our cohort of such women who were...
Women with a history of venous thromboembolisms (VTEs) and/or thrombophilia are at increased risk of VTE during pregnancy. We analysed our cohort of such women who were treated with a prophylactic doses of dalteparin. 152 pregnant women with 179 pregnancies were classified into 3 groups: (1) previous VTE without thrombophilia (122 pregnancies); (2) previous VTE with thrombophilia (26 pregnancies) and (3) thrombophilia only (31 pregnancies). They were treated with prophylactic dalteparin in the prepartum and postpartum periods or only in the postpartum period. Occurrences of symptomatic VTE and bleeding episodes were followed, as well as dalteparin discontinuation and anti-Xa activity. Symptomatic deep vein thrombosis occurred in 4 women (2.2%) with 2 episodes in group 1 (in the postpartum period) and 2 episodes in group 2 (one in the prepartum and another in the postpartum period). Seven episodes (3.9%) of minor bleeding occurred. Dalteparin was not stopped in any women. Anti-Xa levels were within the prophylactic range. Our real-world data show a low incidence of thrombosis and minor bleeding in pregnant women treated with prophylactic dalteparin. The incidence of recurrent VTE was lower than that reported in women with similar risk, but without prophylactic anticoagulation.
Topics: Female; Humans; Pregnancy; Dalteparin; Venous Thromboembolism; Pregnant Women; Risk Factors; Venous Thrombosis; Heparin, Low-Molecular-Weight; Thrombophilia; Hemorrhage; Anticoagulants
PubMed: 36113126
DOI: 10.1177/00033197221126244 -
The American Journal of Nursing Oct 2019
Topics: Anticoagulants; Child; Child, Preschool; Dalteparin; Humans; Infant; Venous Thromboembolism
PubMed: 31567246
DOI: 10.1097/01.NAJ.0000586148.11015.7e -
The New England Journal of Medicine Sep 2011
Topics: Anticoagulants; Critical Illness; Dalteparin; Female; Heparin; Humans; Male; Venous Thrombosis
PubMed: 21992138
DOI: 10.1056/NEJMc1108392 -
BMJ Case Reports Oct 2016Drug fever caused by dalteparin-sodium (DS), a low-molecular-weight derivative of heparin, is neither listed in the official drug information and nor published as a case...
Drug fever caused by dalteparin-sodium (DS), a low-molecular-weight derivative of heparin, is neither listed in the official drug information and nor published as a case report until today. A preterm infant, born at 26 weeks of gestation, developed fever 2 days after starting a treatment with DS for an intracardial thrombus. The fever reverses soon after changing the treatment to unfractionated heparin and reappeared after reintroduction of DS. Once again, after discontinuing DS, the infant regained normothermia. Bacterial and viral infections, tissue damage, impaired liver or kidney function, preservative agents and comedications could be ruled out as fever origin. By using the Naranjo adverse drug reaction (ADR) probability scale and the Liverpool ADR causality assessment tool, this case can be classified as 'probable ADR' and 'definite ADR'. This is the first case report of a drug fever caused by the low-molecular-weight heparin DS in a preterm infant.
Topics: Anticoagulants; Dalteparin; Fever; Heart Diseases; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Thrombosis
PubMed: 27737872
DOI: 10.1136/bcr-2016-217621