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Nephron. Clinical Practice 2012Low-molecular-weight heparins are being increasingly used as an alternative to unfractionated heparin for anticoagulation of the haemodialysis (HD) circuit. Data on...
BACKGROUND
Low-molecular-weight heparins are being increasingly used as an alternative to unfractionated heparin for anticoagulation of the haemodialysis (HD) circuit. Data on dalteparin use in high-flux HD and haemodiafiltration (HDF) are limited. We examined the safety and efficacy of dalteparin in this setting to enable recommendations on the optimal dose range.
METHODS
This prospective study was conducted in a single dialysis unit. Subjects who had been receiving dalteparin for at least 10 HD sessions were studied. Anti-Xa activity was measured for all subjects at the start of the HD session, at 60 min into HD and at the end of dialysis.
RESULTS
55 subjects were studied. None had detectable anti-Xa activity at the start of the session. Using adequacy criteria based on target anti-Xa activity >0.4 IU/ml at 1 h and <0.4 IU/ml at the end of dialysis, 39 (71%) patients had adequate anticoagulation, 12 (22%) patients were under-anticoagulated and 4 (7%) were over-anticoagulated. The mean dose in the adequately anticoagulated group was 60.7 ± 11.7 IU/kg, in the under-anticoagulated group 39.3 ± 9.6 IU/kg and in the over-anticoagulated group 70.1 ± 14.6 IU/kg. The optimal dose of dalteparin appears to be 60 ± 10 IU/kg, which facilitates the achievement of the target anti-Xa activity in the range of 0.4-0.75 IU/ml at 1 h and <0.4 IU/ml at the session end.
CONCLUSION
Dalteparin is a safe and effective anticoagulant for patients on high-flux HD and HDF. The optimal dose appears to be 60 ± 10 IU/kg. The desirable target range of anti-Xa activity is 0.4-0.75 at 1 h and <0.4 IU/ml at the session end.
Topics: Aged; Anticoagulants; Dalteparin; Female; Hemodiafiltration; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis
PubMed: 23548465
DOI: 10.1159/000348830 -
Lancet (London, England) Feb 2015
Topics: Dalteparin; Female; Fibrinolytic Agents; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombophilia
PubMed: 25706216
DOI: 10.1016/S0140-6736(15)60287-2 -
Critical Care Medicine Jul 2006
Topics: Animals; Anticoagulants; Dalteparin; Fibrinolytic Agents; Liver; Liver Diseases; Rats; Reperfusion Injury; Syndrome
PubMed: 16801867
DOI: 10.1097/01.CCM.0000221924.87300.25 -
Lancet (London, England) Feb 2015
Topics: Dalteparin; Female; Fibrinolytic Agents; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombophilia
PubMed: 25706214
DOI: 10.1016/S0140-6736(15)60285-9 -
Dalteparin thromboprophylaxis for critically ill medical-surgical patients with renal insufficiency.Journal of Critical Care Dec 2005Thromboprophylaxis with low-molecular-weight heparin (LMWH) may be more effective than unfractionated heparin but also more likely to bioaccumulate and potentially cause... (Clinical Trial)
Clinical Trial
PURPOSE
Thromboprophylaxis with low-molecular-weight heparin (LMWH) may be more effective than unfractionated heparin but also more likely to bioaccumulate and potentially cause bleeding in patients with renal insufficiency. The objectives of this study were to assess, among medical-surgical patients in the intensive care unit receiving dalteparin 5,000 IU daily for thromboprophylaxis, (1) the relationship between renal dysfunction and LMWH bioaccumulation as measured by trough anti-Xa levels, (2) the relationship between renal dysfunction and risk of bleeding as measured by a surrogate marker (peak anti-Xa levels), and (3) the relationship between anti-Xa levels, bleeding events, and thrombotic events.
MATERIALS AND METHODS
In this prospective single-center cohort study, we enrolled patients 18 years or older, expected to stay 72 hours or longer, and with a creatinine clearance 30 mL/min or higher at intensive care unit admission. We administered 5,000 IU dalteparin subcutaneously each day. The main phase 1 objective was to detect bioaccumulation of dalteparin by measuring trough anti-Xa levels (22-23 hours post dalteparin). The main phase 2 objective was to examine the relationship between renal dysfunction and peak anti-Xa levels (4 hours post dalteparin). We recorded creatinine clearance daily and bleeding and thrombotic events, blinded to anti-Xa levels.
RESULTS
We enrolled 19 patients aged 62.7 (13.2) years with an APACHE II score of 23.5 (9.4). We measured trough anti-Xa levels on 185 occasions in 19 patients; we measured peak anti-Xa levels on 113 occasions in 11 patients. We identified no bioaccumulation of LMWH in this study, as detected by trough anti-Xa levels. Most peak anti-Xa levels were in the conventional prophylactic range.
CONCLUSIONS
When administered in prophylactic doses to critically ill patients with a wide range of calculated creatinine clearances, we found no evidence of bioaccumulation of dalteparin. If dalteparin does not bioaccumulate, it may be an attractive alternative agent for thromboprophylaxis.
Topics: Anticoagulants; Creatinine; Dalteparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Intensive Care Units; Linear Models; Male; Metabolic Clearance Rate; Middle Aged; Ontario; Prospective Studies; Renal Insufficiency; Single-Blind Method; Venous Thrombosis
PubMed: 16310608
DOI: 10.1016/j.jcrc.2005.09.009 -
Supportive Care in Cancer : Official... Jul 2017International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided...
BACKGROUND
International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146-53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs. 17%; p = 0.011). To measure the economic value of secondary VTE prophylaxis with dalteparin, a patient-level pharmacoeconomic analysis was conducted from the Austrian and French healthcare system perspectives.
METHODS
Chapter 1 Healthcare resource use collected during the CLOT trial was extracted and converted into direct cost estimates. Incremental cost differences between the dalteparin and VKA groups were then combined with health state utilities to measure the cost per quality-adjusted life year (QALY) gained.
RESULTS
The dalteparin group had significantly higher costs than the VKA group in both countries (Austria: dalteparin = €2687 vs. VKA = €2012; France: dalteparin = €2053 vs. VKA = €1352: p < 0.001). However, when the incremental costs were combined with the utility gain, dalteparin had a cost of €6600 and €4900 per QALY gained in Austria and France, respectively. The analyses in patients with renal impairment suggested an even better economic profile, with the cost per QALY gained being less than €4000 in both countries.
CONCLUSIONS
Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.
Topics: Anticoagulants; Austria; Cost-Benefit Analysis; Dalteparin; Female; France; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recurrence; Venous Thromboembolism; Vitamin K
PubMed: 28204995
DOI: 10.1007/s00520-017-3610-2 -
Thrombosis and Haemostasis Jul 2024In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE.
METHODS
The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding.
RESULTS
In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group.
CONCLUSION
The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE.
Topics: Humans; Pyridones; Pyrazoles; Dalteparin; Hemorrhage; Neoplasms; Female; Venous Thromboembolism; Male; Middle Aged; Aged; Recurrence; Anticoagulants; Time Factors; Factor Xa Inhibitors; Treatment Outcome; Adult
PubMed: 38196077
DOI: 10.1055/s-0043-1778642 -
Journal of Obstetrics and Gynaecology :... May 2019A systematic review of studies published between 1 January 1985 and 31 August 2017 was performed to analyse the efficacy of the low-molecular-weight heparin, dalteparin,...
A systematic review of studies published between 1 January 1985 and 31 August 2017 was performed to analyse the efficacy of the low-molecular-weight heparin, dalteparin, in venous thromboembolism (VTE) treatment and prophylaxis during pregnancy, and to evaluate dosing practices, anticoagulant monitoring and adverse events. A therapeutic dosing throughout pregnancy or followed by reduced doses effectively prevented VTE recurrence. Anti-factor Xa activity was the most commonly used method of dose monitoring. The risk of bleeding with dalteparin was generally minor. Major bleeding was observed when a high dose of dalteparin was employed during (or close to) delivery, or postpartum. Other adverse events were minor. Disparity exists in VTE treatment and thromboprophylaxis, with wide variety in the dosing regimens, treatment strategies and monitoring practices employed. Large randomised controlled trials are warranted but due to ethical reasons, and the rarity of VTE-associated obstetric complications, case-control, registry and large observational studies present more likely options.
Topics: Adult; Anticoagulants; Dalteparin; Female; Humans; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Cardiovascular; Treatment Outcome; Venous Thromboembolism
PubMed: 30426808
DOI: 10.1080/01443615.2018.1499713 -
Thrombosis Research Mar 2017Ambulatory cancer patients at high-risk for venous thromboembolism (VTE) can be identified using a validated risk score (Khorana score). We evaluated the benefit of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ambulatory cancer patients at high-risk for venous thromboembolism (VTE) can be identified using a validated risk score (Khorana score). We evaluated the benefit of outpatient thromboprophylaxis with dalteparin in high-risk patients in a multicenter randomized study.
METHODS
Cancer patients with Khorana score≥3 starting a new systemic regimen were screened for VTE and if negative randomized to dalteparin 5000units daily or observation for 12weeks. Subjects were screened with lower extremity ultrasounds every 4weeks on study and with chest CT at 12weeks. The primary efficacy endpoint was all VTE over 12weeks and primary safety endpoint was clinically relevant bleeding events over 13weeks. The study was terminated early due to low accrual.
RESULTS
Of 117 enrolled patients, 10 (8.5%) had VTE on baseline screening and were not randomized. Of 98 randomized patients, VTE occurred in 12% (N=6/50) of patients on dalteparin and 21% (N=10/48) on observation (hazard ratio, HR 0.69, 95% CI 0.23-1.89). Major bleeding was similar (N=1) in each arm but clinically relevant bleeding was higher in dalteparin arm (N=7 versus 1 on observation) (HR=7.0, 95% CI 1.2-131.6). There was no difference in overall survival.
CONCLUSIONS
Thromboprophylaxis is associated with a non-significantly reduced risk of VTE and significantly increased risk of clinically relevant bleeding in this underpowered study. The Khorana score successfully identifies patients with high incidence of VTE both at baseline and during treatment. Future studies should continue to focus on risk-adapted approaches to reduce the burden of VTE in cancer.
TRIAL REGISTRATION
clinicaltrials.gov identifier: NCT00876915.
Topics: Aged; Anticoagulants; Dalteparin; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Treatment Outcome; Venous Thromboembolism
PubMed: 28139259
DOI: 10.1016/j.thromres.2017.01.009 -
Archives of Iranian Medicine Jul 2008Retinal vein occlusion is the second most common vascular disease of retina after diabetic retinopathy, affecting 1.6% of the population above the age of 40. The aim of... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Retinal vein occlusion is the second most common vascular disease of retina after diabetic retinopathy, affecting 1.6% of the population above the age of 40. The aim of this study was to compare the effect of dalteparin and aspirin in patients with recent-onset branch retinal vein occlusion.
METHODS
A randomized clinical trial was conducted on patients with branch retinal vein occlusion of less than 30 days' duration. Ophthalmic, systemic, and hematologic evaluations were made. Visual acuity was measured with Early Treatment Diabetic Retinopathy Study chart. Patients in the dalteparin group received subcutaneous dalteparin 100 IU/kg twice daily for 10 days, then 100 IU/kg once daily for another 10 days while the patients in the aspirin group were given aspirin 100 mg daily throughout the study.
RESULTS
Seventy-eight patients were enrolled, 37 in the dalteparin and 41 in the aspirin group. The patients were followed for six months. The visual outcomes of the two groups were compared. Although dalteparin improved mean visual acuity slightly more than aspirin, no statistically significant differences were found between the groups at one (P=0.37), two (P=0.16), three (P=0.11), or six (P=0.13) months. Resolution of macular edema and development of new vessels made no statistically significant difference between the groups [(P=0.08) and (P=0.49), respectively].
CONCLUSION
In recent-onset branch retinal vein occlusion, no significant difference was found in the final visual acuity between the patients treated by dalteparin or aspirin. A further study with larger sample size is recommended.
Topics: Aspirin; Dalteparin; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Retinal Vein Occlusion; Time Factors
PubMed: 18588374
DOI: No ID Found