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The Journal of Trauma Jun 2002Ischemia/reperfusion-induced polymorphonuclear neutrophil leukocyte (PMN) adhesion and extravasation are pivotal for the development of postinjury multiple organ...
BACKGROUND
Ischemia/reperfusion-induced polymorphonuclear neutrophil leukocyte (PMN) adhesion and extravasation are pivotal for the development of postinjury multiple organ failure. We hypothesized that the deleterious microcirculatory consequences of hemorrhagic shock (HS) could be altered by low-molecular-weight heparin (LMWH) therapy. Our aim was to investigate the effects of dalteparin sodium on leukocyte-endothelial cell interactions when LMWH treatment was initiated before HS or during resuscitation.
METHODS
Anesthetized dogs underwent HS (40 mm Hg mean arterial pressure for 60 minutes) and resuscitation either with shed blood or with lactated Ringer's (LR) solution. LMWH or conventional heparin sodium pretreatment was administered subcutaneously before hemorrhage; or LMWH was given intravenously during resuscitation. Mesenteric postcapillary venules were observed by intravital video microscopy before and after HS, and 60 minutes, 120 minutes, and 180 minutes after resuscitation, and leukocyte rolling and firm adherence were determined.
RESULTS
HS significantly increased PMN rolling and adhesion in the mesenteric microcirculation. LMWH, but not heparin sodium pretreatment, significantly inhibited both primary and secondary interactions. LMWH treatment was also effective when initiated during resuscitation. LMWH exerted the same inhibitory effect regardless of the type of resuscitation.
CONCLUSION
LMWH treatment during resuscitation effectively inhibits PMN rolling and adhesion.
Topics: Animals; Anticoagulants; Blood Pressure; Cell Adhesion Molecules; Dalteparin; Dogs; Heparin, Low-Molecular-Weight; Resuscitation; Shock, Hemorrhagic; Splanchnic Circulation
PubMed: 12045631
DOI: 10.1097/00005373-200206000-00007 -
Clinical and Applied... Oct 2016In a randomized trial (ie, Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In a randomized trial (ie, Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]) that evaluated secondary prophylaxis of recurrent venous thromboembolism (VTE) in patients with cancer, dalteparin reduced the relative risk by 52% compared to oral vitamin K antagonists (VKAs; hazard ratio = 0.48, P = .002). A recent subgroup analysis in patients with moderate to severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs 17%; P = .011). To measure the economic value of dalteparin in these populations, a pharmacoeconomic analysis was conducted from the Dutch health-care system perspective.
METHODS
Resource utilization data contained within the CLOT trial database were extracted and converted into direct cost estimates. Univariate analysis was then conducted to compare the total cost of therapy between patients randomized to dalteparin or VKA therapy. Health state utilities were then measured in 24 members of the general public using the time trade-off technique.
RESULTS
When all of the cost components were combined for the entire population (n = 676), the dalteparin group had significantly higher overall costs than the VKA control group (dalteparin = €2375 vs VKA = €1724; P < .001). However, dalteparin was associated with a gain of 0.14 (95% confidence interval [CI]: 0.10-0.18) quality-adjusted life years (QALYs) over VKA. When the incremental cost was combined with the utility gain, dalteparin had a cost of €4,697 (95% CI: €3824-€4951) per QALY gained.
CONCLUSION
Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.
Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cost-Benefit Analysis; Dalteparin; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Recurrence; Renal Insufficiency; Venous Thromboembolism; Vitamin K; Young Adult
PubMed: 27436663
DOI: 10.1177/1076029616658118 -
Blood Aug 2000
Topics: Alopecia; Anticoagulants; Child; Dalteparin; Female; Humans; Venous Thrombosis
PubMed: 10979669
DOI: No ID Found -
Pharmacotherapy Nov 2005To determine the rate of bleeding and thromboembolic events within 1 month of outpatient dalteparin therapy in veterans with mechanical heart valves, to evaluate...
STUDY OBJECTIVES
To determine the rate of bleeding and thromboembolic events within 1 month of outpatient dalteparin therapy in veterans with mechanical heart valves, to evaluate potential risk factors associated with these events, and to examine the prescribing patterns of dalteparin in this patient population.
DESIGN
Single-center retrospective electronic chart review.
SETTING
Large, academically affiliated Veterans Affairs hospital.
SUBJECTS
Thirty-eight men with mechanical heart valves who received outpatient prescriptions for dalteparin from October 1, 1998-June 30, 2003.
MEASUREMENTS AND MAIN RESULTS
Charts were reviewed for thromboembolic and bleeding events. Demographic, clinical, and drug utilization variables were assessed. The associations of adverse events with potential risk factors, indication for dalteparin therapy, and prescribing clinic were analyzed. Sixty-four dalteparin regimens were evaluated. No thromboembolic events were reported in any case within 1 month after receiving dalteparin for thromboembolic prophylaxis during warfarin interruption for periprocedural anticoagulation or for anticoagulation during an unintentional subtherapeutic international normalized ratio. Bleeding events occurred in 15 (23%) of the 64 regimens. Most bleeding events resolved spontaneously and without intervention. No potential risk factors for bleeding were identified.
CONCLUSION
Dalteparin appeared to be a safe, effective means of short-term thromboembolic prophylaxis in this population of ambulatory male veterans with mechanical heart valves. Large, randomized, controlled, prospective trials are warranted.
Topics: Aged; Aged, 80 and over; Anticoagulants; Dalteparin; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Outpatients; Thromboembolism; Veterans
PubMed: 16232019
DOI: 10.1592/phco.2005.25.11.1560 -
Medicina Clinica Sep 2002
Topics: Aged; Aged, 80 and over; Anticoagulants; Dalteparin; Female; Humans; Thrombocytopenia
PubMed: 12372177
DOI: 10.1016/s0025-7753(02)73429-5 -
Blood Coagulation & Fibrinolysis : An... Jun 1998Seventeen women with previously verified thromboembolism were included in a pharmacokinetic evaluation of dalteparin during the third trimester of pregnancy. The... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Seventeen women with previously verified thromboembolism were included in a pharmacokinetic evaluation of dalteparin during the third trimester of pregnancy. The bioavailability of morning subcutaneous administration of dalteparin (crossover study) was also compared with that in the evening. Fifteen women injected themselves subcutaneously with 5000 IU and two with 2500 IU dalteparin once daily. An anti-FXa activity of 0.20-0.40 IU/ml 3 h after injection was obtained. The means +/- SD, when comparing morning and evening doses for 5000 IU, were: Cmax 0.21 +/- 0.05 and 0.20 +/- 0.05 IU anti-FXa/ml, AUC 0-24 h 1.97 +/- 0.46 and 1.93 +/- 0.55 IU x h/ml and tmax 3.71 +/- 0.89 and 4.32 +/- 1.60 h, respectively (NS). The two regimens were equivalent. A measurable anticoagulant effect was still observed 16 h after injection of 5000 IU dalteparin. The half-lives after a morning and an evening dose of 5000 IU dalteparin were 4.92 +/- 2.80 and 3.87 +/- 1.15 h, respectively (NS). There were no changes in thrombin marker levels during the two pharmacokinetic measurements.
Topics: Adult; Anticoagulants; Antithrombin III; Area Under Curve; Circadian Rhythm; Cross-Over Studies; Dalteparin; Dose-Response Relationship, Drug; Factor Xa; Factor Xa Inhibitors; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Half-Life; Humans; Peptide Fragments; Peptide Hydrolases; Pregnancy; Pregnancy Trimester, Third; Prothrombin; Therapeutic Equivalency; Thrombosis; Time Factors
PubMed: 9690805
DOI: 10.1097/00001721-199806000-00006 -
Canadian Family Physician Medecin de... Feb 2005A few years ago I suffered from pulmonary emboli. My physician recommended I use dalteparin during this pregnancy although, during my previous pregnancy, I had received... (Review)
Review
QUESTION
A few years ago I suffered from pulmonary emboli. My physician recommended I use dalteparin during this pregnancy although, during my previous pregnancy, I had received subcutaneous heparin injections three times daily. Is dalteparin the same as heparin?
ANSWER
: Based on the best available evidence from mostly small prospective case series, retrospective reports, and placental perfusion studies, low-molecular-weight heparins (LMWHs), such as dalteparin, are a safe and convenient alternative to heparin during pregnancy for both mothers and fetuses.
Topics: Anticoagulants; Dalteparin; Female; Heparin, Low-Molecular-Weight; Humans; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism
PubMed: 15751560
DOI: No ID Found -
American Journal of Physical Medicine &... Sep 2003To determine differences between dalteparin and enoxaparin in patients with spinal cord injury. (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
OBJECTIVE
To determine differences between dalteparin and enoxaparin in patients with spinal cord injury.
DESIGN
This prospective, randomized, open-label study was performed as a multiple hospital trial in a large urban setting. A total of 100 patients with acute (<3 mo) spinal cord injury were recruited. A total of 95 patients met all inclusion criteria. Fifty received enoxaparin, and 45 received dalteparin. Main outcome measures included deep venous thrombosis, bleeding, compliance, Short Form-12 Health Status Survey, satisfaction, and medication/labor costs. Patients were randomized to receive 30 mg of enoxaparin subcutaneously every 12 hr or 5000 IU of dalteparin subcutaneously once daily. Prophylaxis was continued for 3 mo for motor-complete and 2 mo for motor-incomplete patients.
RESULTS
Six percent of the patients developed deep venous thrombosis while receiving enoxaparin and 4% while receiving dalteparin (chi2 = 0.44, df = 1, P = 0.51). Four percent developed bleeding while receiving dalteparin and 2% while receiving enoxaparin (chi2 = 0.13, df = 1, P = 0.72). No differences were noted in compliance, health status, or most of the satisfaction measures. It was, however, noted that after being discharged home, the patients receiving enoxaparin rated the shots significantly more inconvenient (two injections per day) compared with taking three pills per day, than those receiving dalteparin (one injection per day, P < 0.05). The cost of the medication was 1101 US dollars/mo for enoxaparin (two injections per day) and 750 US dollars/mo for dalteparin (one injection per day).
CONCLUSION
Similar compliance, health status, deep venous thrombosis, and bleeding rates were found between dalteparin and enoxaparin.
Topics: Adolescent; Adult; Aged; Dalteparin; Enoxaparin; Female; Fibrinolytic Agents; Health Status Indicators; Hemorrhage; Humans; Male; Middle Aged; Patient Compliance; Patient Satisfaction; Prospective Studies; Spinal Cord Injuries; Surveys and Questionnaires; Treatment Outcome; Venous Thrombosis
PubMed: 12960909
DOI: 10.1097/01.PHM.0000083671.27501.47 -
BMJ Open Nov 2020In the 'Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism' (SELECT-D) trial, rivaroxaban... (Clinical Trial)
Clinical Trial
OBJECTIVES
In the 'Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism' (SELECT-D) trial, rivaroxaban showed relatively low venous thromboembolism (VTE) recurrence but higher bleeding compared with dalteparin in patients with cancer. We aim to calculate the cost-effectiveness and budget impact of rivaroxaban compared with dalteparin in patients with cancer at risk of recurrent VTE.
SETTING
We built a Markov model to calculate the cost-effectiveness from a societal perspective over a 5-year time horizon for the Dutch healthcare setting.
PARTICIPANTS
A hypothetical cohort of 1000 cancer patients with VTE entered the model with baseline characteristics based on the SELECT-D trial.
INTERVENTION
Six months of treatment with rivaroxaban (15 mg two times per day for first 3 weeks followed by 20 mg once daily) was compared with 6 months of treatment with dalteparin (200 IU/kg daily during month 1 followed by 150 IU/kg daily).
PRIMARY AND SECONDARY OUTCOME MEASURES
The primary outcome of the cost-effectiveness analysis was the incremental cost-effectiveness ratio (ICER). The robustness of the model was evaluated in probabilistic and univariate sensitivity analyses. A budget impact analysis was performed to calculate the total annual financial consequences for a societal perspective in the Netherlands.
RESULTS
In the base case and all scenarios, rivaroxaban were cost-saving while also slightly improving the patient's health, resulting in economically dominant ICERs. In the probabilistic sensitivity analysis, 77.8% and 98.7% of the simulations showed rivaroxaban to be cost-saving and more effective for a 5-year and 6-month time horizon, respectively. Rivaroxaban can save up to €11 326 763 (CI €5 164 254 to €17 363 231) in approximately 8000 cancer patients with VTE per year compared with dalteparin based on a 1-year time horizon.
CONCLUSIONS
Treatment with rivaroxaban is economically dominant over dalteparin in patients with cancer at risk for recurrent VTE in the Netherlands. The use of rivaroxaban instead of dalteparin can save over €10 million per year, primarily driven by the difference in drug costs.
Topics: Aged; Anticoagulants; Cost-Benefit Analysis; Dalteparin; Female; Humans; Male; Neoplasms; Netherlands; Rivaroxaban; Venous Thromboembolism
PubMed: 33444193
DOI: 10.1136/bmjopen-2020-039057 -
Journal of Thrombosis and Haemostasis :... Aug 2007The risk of decreased bone mineral density (BMD) with prophylactic dose long-term low-molecular-weight heparin (LMWH) is unknown. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The risk of decreased bone mineral density (BMD) with prophylactic dose long-term low-molecular-weight heparin (LMWH) is unknown.
OBJECTIVES
We sought to determine whether long-term prophylactic dalteparin in pregnancy leads to loss of BMD.
PATIENTS/METHODS
Patients in a substudy of an ongoing multicenter randomized trial investigating the effect of antepartum dalteparin prophylaxis on pregnancy outcomes in thrombophilic pregnant women were randomized to either dalteparin 5000 U s.c. daily until 20 weeks and then 5,000 U s.c. q12 h until >37 weeks or to the control group. The primary outcome was absolute spine BMD at six weeks postpartum.
RESULTS
Of 77 patients eligible for the BMD substudy, 62 were analyzed. 33 patients received a mean of 212 days of dalteparin in the intervention group. 29 patients received a mean of 38 days of postpartum dalteparin in the control group. There was no difference in mean BMD between the intervention (1.11 g cm(-2)) and the control groups (1.14 g cm(-2)). Similarly, there was no difference in T-scores; the difference of -0.34 (95% confidence interval -0.93 to +0.25) in favor of the control group excludes a clinically important increase in fracture risk.
CONCLUSIONS
Our results suggest that the use of long-term prophylactic dalteparin in pregnancy is not associated with a significant decrease in BMD.
CLINICAL TRIAL REGISTRATION
ISRCTN87441504 at http://www.controlled-trials.com.
Topics: Adult; Anticoagulants; Bone Density; Bone Diseases, Metabolic; Dalteparin; Female; Humans; Middle Aged; Osteoporosis; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Thrombophilia; Treatment Outcome
PubMed: 17663731
DOI: 10.1111/j.1538-7836.2007.02634.x