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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 -
Veterinary Clinical Pathology Sep 2017The calibrated automated thrombogram (CAT) is a functional thrombin generation (TG) assay that may provide a new approach for monitoring anticoagulant therapy in dogs....
BACKGROUND
The calibrated automated thrombogram (CAT) is a functional thrombin generation (TG) assay that may provide a new approach for monitoring anticoagulant therapy in dogs. The effects of dalteparin on TG variables in dogs are unknown.
OBJECTIVES
Objectives were to establish normal TG variable ranges in dogs and measure the in vitro TG variables in canine pooled platelet-poor plasma (PPP) spiked with different dalteparin concentrations.
METHODS
In the first experiment, plasma samples from 25 adult healthy Beagle dogs and 11 client-owned healthy dogs of multiple breeds was measured individually for obtaining normal TG values. In the second experiment, separate pools of the remaining PPP from 24 of the 25 previous adult Beagles and from 45 different client-owned dogs were spiked with dalteparin at 9 concentrations with increasing anti-factor Xa (anti-FXa) activity. Activated partial thromboplastin time, tissue factor-induced TG, and anti-FXa activity were measured for each concentration. Concentration-response relationships were determined with ADAPT v.5, using various nonlinear regression models for stimulatory or inhibitory effects.
RESULTS
Thrombin generation ranges of client-owned dogs and Beagles were equivalent only for time-to-peak (P < .05). In vitro dalteparin resulted in a concentration-dependent decrease in endogenous thrombin potential (ETP) in pooled PPP. The estimated dalteparin concentration that produced half the maximal inhibition of baseline ETP (IC ) was 0.289 U/mL. Thrombin generation and anti-FXa activity were more sensitive than APTT to detect the effects of dalteparin.
CONCLUSIONS
The CAT assay can measure the effects of dalteparin in canine plasma, resulting in significant dose-dependent decreases in ETP, prompting further in vivo investigation.
Topics: Animals; Anticoagulants; Dalteparin; Dogs; Dose-Response Relationship, Drug; Female; In Vitro Techniques; Male; Thrombin
PubMed: 28605123
DOI: 10.1111/vcp.12510 -
Pediatric Blood & Cancer Aug 2022Data from registrational trials of pediatric venous thromboembolism (VTE) treatment are sparse, especially among cancer patients. We conducted a prospective,...
Data from registrational trials of pediatric venous thromboembolism (VTE) treatment are sparse, especially among cancer patients. We conducted a prospective, multicenter, open-label trial (NCT00952380) on dose-finding, safety, and efficacy (measured by 90-day risks of clinically relevant bleeding [CRB] and symptomatic recurrent VTE [srVTE]) of twice-daily subcutaneous dalteparin for acute VTE treatment in patients ≤18 years old. Among 38 patients (cancer, n = 26; noncancer, n = 12), median dalteparin dose requirements per kilogram varied with age but not cancer status. Risks of CRB and srVTE were <4% in cancer and noncancer subgroups. Dalteparin is an important FDA-approved treatment for pediatric VTE, particularly with cancer.
Topics: Adolescent; Anticoagulants; Child; Dalteparin; Hemorrhage; Humans; Neoplasms; Prospective Studies; Venous Thromboembolism
PubMed: 35678616
DOI: 10.1002/pbc.29764 -
Mayo Clinic Proceedings Feb 2022To maintain living, interactive evidence (LIvE) on the benefits and harms of different treatment options in adults with cancer-associated thrombosis (CAT). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To maintain living, interactive evidence (LIvE) on the benefits and harms of different treatment options in adults with cancer-associated thrombosis (CAT).
METHODS
We have used a novel LIvE synthesis framework to maintain this living, interactive systematic review since September 19, 2018. Randomized controlled trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin for CAT are included in this analysis. Details of LIvE synthesis framework are available at the website https://cat.network-meta-analysis.com.
RESULTS
The results are constantly updated as new information becomes available (https://cat.network-meta-analysis.com/CAT.html). The living, interactive systematic review currently includes 4 randomized controlled trials (N=2894). Direct comparisons show that DOACs significantly decrease recurrent venous thromboembolism (VTE) events compared with dalteparin (odds ratio [OR], 0.59; 95% CI, 0.41 to 0.86; I, 25%) without significantly increasing major bleeding (OR, 1.34; 95% CI, 0.83 to 2.18; I, 28%). Mixed treatment comparisons show that apixaban (OR, 0.41; 95% credible interval [CrI], 0.16 to 0.95) and rivaroxaban (OR, 0.58; 95% CrI, 0.37 to 0.90) significantly decrease VTE recurrent events compared with dalteparin. Edoxaban significantly increases major bleeding compared with dalteparin (OR, 1.73; 95% CrI, 1.04 to 3.16), and rivaroxaban significantly increases clinically relevant nonmajor bleeding compared with dalteparin and other DOACs. There are no significant differences between DOACs in terms of VTE recurrences and major bleeding.
CONCLUSION
DOACs should be considered a standard of care for the treatment of CAT except in patients with a high risk of bleeding. Current evidence favors the use of apixaban for the treatment of CAT among other DOACs.
REGISTRATION
Open Science Framework (https://osf.io/dth86).
Topics: Administration, Oral; Anticoagulants; Dalteparin; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Network Meta-Analysis; Venous Thromboembolism
PubMed: 34172290
DOI: 10.1016/j.mayocp.2020.10.041 -
American Journal of Physical Medicine &... Dec 2001To assess the clinical and economic consequences of a formulary switch from enoxaparin to dalteparin as first-line prophylaxis for deep-vein thrombosis in patients... (Comparative Study)
Comparative Study
OBJECTIVE
To assess the clinical and economic consequences of a formulary switch from enoxaparin to dalteparin as first-line prophylaxis for deep-vein thrombosis in patients undergoing inpatient rehabilitation after total hip arthroplasty or total knee arthroplasty.
DESIGN
Retrospective cohort study.
RESULTS
There were 461 patients eligible for the study. The age-adjusted risk of a deep-vein thrombosis event confirmed by duplex ultrasonography among patients treated with dalteparin was substantially lower than among patients treated with enoxaparin, whereas the age-adjusted risk of a bleeding event in the dalteparin group was also lower than that in the enoxaparin group. Adjusted per capita costs of deep-vein thrombosis prophylaxis during the rehabilitation stay were $129 lower among subjects treated with dalteparin.
CONCLUSION
The switch to dalteparin as a first-line therapy for deep-vein thrombosis prophylaxis in the rehabilitation period after total hip arthroplasty or total knee arthroplasty has led to substantial cost savings for Kessler Institute without compromising patient care.
Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Costs and Cost Analysis; Dalteparin; Enoxaparin; Female; Humans; Male; Middle Aged; New Jersey; Retrospective Studies; Venous Thrombosis
PubMed: 11821667
DOI: 10.1097/00002060-200112000-00004 -
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 -
American Journal of Health-system... Dec 2002
Topics: Arthroplasty, Replacement, Knee; Dalteparin; Humans; Postoperative Care; Retrospective Studies; Thromboembolism
PubMed: 12503344
DOI: 10.1093/ajhp/59.24.2451 -
The Journal of Cardiovascular Nursing Jul 2001Traditionally administered unfractionated heparin (UH) is a heterogeneous mixture of polysaccharide chains of varying length. Heparin is now available in new... (Review)
Review
Traditionally administered unfractionated heparin (UH) is a heterogeneous mixture of polysaccharide chains of varying length. Heparin is now available in new formulations, most notably the low-molecular-weight heparins (LMWHs), which possess pharmacology that is similar to but distinct from UH. Key advantages of LMWHs include improved bioavailability and longer half-life, more predictable anticoagulation that requires less laboratory monitoring, and fewer serious side effects. The article reviews the pharmacology of heparin and discusses the addition of LMWHs to the family of anticoagulant drugs.
Topics: Anticoagulants; Dalteparin; Enoxaparin; Heparin, Low-Molecular-Weight; Humans; Nadroparin; Venous Thrombosis
PubMed: 11419668
DOI: 10.1097/00005082-200107000-00008 -
The Medical Journal of Australia Mar 1998To assess the efficacy, safety and cost savings of home treatment of lower-limb deep venous thrombosis (DVT).
OBJECTIVE
To assess the efficacy, safety and cost savings of home treatment of lower-limb deep venous thrombosis (DVT).
SETTING
A hospital-in-the-home treatment program.
PATIENTS
One hundred patients with acute lower limb DVT (53 proximal, 47 distal), and no contraindication to home treatment, were entered into the program from March 1995 to February 1997.
INTERVENTION
All patients received dalteparin, 200 units/kg subcutaneously, once daily for a minimum of five days, with commencement of oral anticoagulation (warfarin) on Day 2. Patients with proximal DVT had lung ventilation-perfusion scans performed and were admitted to hospital for at least 24 hours. Patients with distal DVT were discharged directly to home treatment.
MAIN OUTCOME MEASURES
Clinical responses and the results of sequential duplex ultrasonography at one week, one month, three months and six months.
RESULTS
There were no major, but six minor, bleeding complications, two of which led to dalteparin being withdrawn. Sixteen patients had lung ventilation-perfusion scans showing a high probability of pulmonary embolism. All were asymptomatic, and follow-up for at least three months showed no symptomatic thromboembolic events. Duplex ultrasonography showed progression of thrombosis in the first week of therapy in 13.2% of distal and 2.7% of proximal thromboses. Thereafter, distal DVT improved at a much greater rate than proximal DVT; after six months complete resolution was seen in 60.7% of distal and 18.5% of proximal thromboses, respectively. Cost saving was $197 per bed-day equivalent compared with inpatient care. At 15 months' follow-up, swelling and/or pain was reported by 49% of patients with distal DVT and 66% of those with proximal DVT.
CONCLUSIONS
Once-daily dalteparin therapy for DVT in a hospital-in-the-home setting was safe, efficacious and cost effective. However, DVT resolution is a slow process, with significant long term morbidity.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; Dalteparin; Female; Home Care Services, Hospital-Based; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Thrombosis; Treatment Outcome; Ultrasonography, Doppler, Duplex; Victoria
PubMed: 9549534
DOI: 10.5694/j.1326-5377.1998.tb140160.x -
Canadian Journal of Ophthalmology.... Feb 2008The present study assessed the therapeutic effects of dalteparin in patients who had recent onset central retinal vein occlusion (CRVO) as compared with those of... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The present study assessed the therapeutic effects of dalteparin in patients who had recent onset central retinal vein occlusion (CRVO) as compared with those of acetylsalicylic acid (ASA).
METHODS
Patients with recent onset of CRVO were randomly assigned to receive dalteparin subcutaneously every day for 20 days or ASA daily for the same period. Complete ophthalmic examinations were conducted at baseline and at each follow-up interval: 1 week and 1, 2, 3, 4, and 6 months later. Best-corrected visual acuity was assessed by an investigator blind to the treatment group.
RESULTS
The mean 6-month change in logMAR visual acuity for dalteparin-treated patients was an increase of 5.5 letters (Early Treatment Diabetic Retinopathy Study chart) (-0.11 [SD 0.71] logMAR) and for ASA-treated patients was a decrease of 14 letters (+0.28 [SD 0.79] logMAR), representing a significant difference between the 2 groups (p = 0.016). One patient in the dalteparin group and 14 in the ASA group showed iris neovascularization (NVI) (2.1% vs. 30.4%, p = 0.0001).
INTERPRETATION
Dalteparin was found to be superior to ASA in terms of improving visual acuity and preventing NVI over the first 6 months of treatment. Similar studies are recommended of other newer types of anticoagulants, especially those that could be used orally.
Topics: Administration, Oral; Aspirin; Dalteparin; Female; Fibrinolytic Agents; Humans; Injections, Subcutaneous; Male; Middle Aged; Retinal Vein Occlusion; Treatment Outcome; Visual Acuity
PubMed: 18219348
DOI: 10.3129/i07-190