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Critical Care (London, England) Nov 2020A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are...
BACKGROUND
A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association between initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding.
METHOD
In this retrospective study, all critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis: low (2500-4500 IU tinzaparin or 2500-5000 IU dalteparin), medium (> 4500 IU but < 175 IU/kilogram, kg, of body weight tinzaparin or > 5000 IU but < 200 IU/kg of body weight dalteparin), and high dose (≥ 175 IU/kg of body weight tinzaparin or ≥ 200 IU/kg of body weight dalteparin). Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios with corresponding 95% confidence intervals of death within 28 days from ICU admission. Multivariable models were adjusted for sex, age, body mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis.
RESULTS
A total of 152 patients were included: 67 received low-, 48 medium-, and 37 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. For patients who received high-dose prophylaxis, mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low dose (38.8%), p = 0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13-0.87) among those who received high dose, and 0.88 (95% confidence intervals 0.43-1.83) among those who received medium dose, as compared to those who received low-dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04.
CONCLUSIONS
Among critically ill COVID-19 patients with respiratory failure, high-dose thromboprophylaxis was associated with a lower risk of death and a lower cumulative incidence of thromboembolic events compared with lower doses.
TRIAL REGISTRATION
Clinicaltrials.gov NCT04412304 June 2, 2020, retrospectively registered.
Topics: APACHE; Aged; Anticoagulants; COVID-19; Critical Illness; Dalteparin; Female; Humans; Intensive Care Units; Male; Middle Aged; Retrospective Studies; SARS-CoV-2; Sweden; Thrombosis; Tinzaparin
PubMed: 33225952
DOI: 10.1186/s13054-020-03375-7 -
Talanta Apr 2024This article presents a novel proof of concept for the blood plasma quantification of clinically relevant concentrations of direct oral anticoagulants, DOACs, including...
This article presents a novel proof of concept for the blood plasma quantification of clinically relevant concentrations of direct oral anticoagulants, DOACs, including rivaroxaban and edoxaban, as well as low-molecular-weight heparins, LMWHs, such as enoxaparin and dalteparin, utilising a calibration-free disposable electrochemical sensor with co-facing electrodes. A dose-response curve was generated for rivaroxaban and edoxaban to demonstrate the sensor's ability to detect ≥9.00 ng mL rivaroxaban and quantify it in the 11.0-140 ng mL range. Similarly, the lower detection limit for edoxaban was 12.9 ng mL, with a quantification range of 16.8-140 ng mL. The significance of this sensor lies in its ability to quantify rivaroxaban and edoxaban below 30 ng mL, which is crucial in emergency care centres when patients undergoing DOAC therapy require emergency surgery or reversal of DOACs due to bleeding or ischemic stroke. Furthermore, the sensor can detect ≥0.016 IU mL enoxaparin and ≥0.013 IU mL dalteparin and quantify them in the 0.025-0.75 and 0.019-0.75 IU mL range, respectively. Additionally, a dose-response curve was presented to demonstrate the potential ability of this sensor to quantify factor-Xa inhibitors independently of which DOACs or LMWHs are used. With the assay completed in less than 30 s using a minimal volume of 7 μL sample, the possibility to work at physiological pH and under calibration-free format makes this assay an excellent candidate for point-of-care testing.
Topics: Humans; Factor Xa Inhibitors; Rivaroxaban; Enoxaparin; Dalteparin; Point-of-Care Systems; Anticoagulants; Administration, Oral; Pyridines; Thiazoles
PubMed: 38159356
DOI: 10.1016/j.talanta.2023.125593 -
Clinical Cardiology Mar 2001The FRISC II study addressed two key questions in the management of acute coronary syndromes: is it beneficial to extend low-molecular-weight heparin (LMWH) therapy with... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The FRISC II study addressed two key questions in the management of acute coronary syndromes: is it beneficial to extend low-molecular-weight heparin (LMWH) therapy with dalteparin beyond the initial period of acute treatment; and, is a strategy of early invasive therapy, including angioplasty and surgical revascularization, preferable to a more conservative strategy? The study focused on patients with unstable coronary artery disease (UCAD), that is, angina and non-ST-segment-elevation myocardial infarction (MI). Patients were allocated in a randomized, factorial study design to either an invasive or a conservative management strategy. Within each of these groups, patients were further randomized to receive either 3 months of extended treatment with dalteparin or placebo, following at least 5 days' treatment with open-label dalteparin. After 1 year, patient survival and MI-free survival were significantly higher in the invasive therapy group than in the noninvasive group. Patients who received extended dalteparin treatment had a significantly reduced probability of death or MI after 1 month (relative risk reduction 47%; p = 0.002), a benefit still evident after 60 days, but after 3 months there was no longer any significant clinical advantage compared with placebo. There was, however, a significant reduction in the combined incidence of death, MI, or revascularization at 3 months in the extended dalteparin treatment group (relative risk reduction 13%; p = 0.031). The benefits of extended dalteparin treatment were particularly marked in patients with elevated troponin-T or ST-segment depression. A subgroup analysis of conservatively managed patients who underwent revascularization in the first 45 days revealed that the probability of death or MI at 1 year was significantly lower among patients who received extended dalteparin treatment (relative risk reduction 35%; p = 0.02). Extended dalteparin treatment is, however, associated with a small increase in bleeding risk. In conclusion, early invasive therapy (following combined treatment with aspirin and dalteparin) is recommended in a majority of patients with UCAD. Furthermore, extended dalteparin treatment for up to 45 days is efficacious and well tolerated, and therefore provides a useful "bridge" to revascularization when early revascularization is not immediately available.
Topics: Adult; Angina, Unstable; Anticoagulants; Dalteparin; Female; Humans; Male; Myocardial Infarction; Myocardial Revascularization; Randomized Controlled Trials as Topic; Syndrome; Thrombolytic Therapy; Treatment Outcome
PubMed: 11286312
DOI: 10.1002/clc.4960241303 -
Pathophysiology of Haemostasis and... 2005Ximelagatran represents the first new oral anticoagulant since the introduction of warfarin almost 60 years ago, and has been evaluated for the treatment and prevention... (Review)
Review
Ximelagatran represents the first new oral anticoagulant since the introduction of warfarin almost 60 years ago, and has been evaluated for the treatment and prevention of a range of venous and arterial thromboembolic disorders. The MElagatran THRomboprophylaxis in Orthopaedic surgery (METHRO) and EXpanded PRophylaxis Evaluation Surgery Study (EXPRESS) studies have investigated the efficacy and safety of subcutaneous (s.c.) melagatran followed by oral ximelagatran in preventing venous thromboembolism (VTE) in patients undergoing total hip replacement or total knee replacement. In METHRO II, immediate pre-operative-initiated s.c. melagatran followed by post-operative ximelagatran dose-dependently reduced VTE, with the highest dose (melagatran 3 mg/ximelagatran 24 mg twice daily) associated with a significantly reduced incidence of VTE compared with the low-molecular-weight heparin (LMWH) dalteparin (15.1 vs. 28.2%; p < 0.0001). In METHRO III, the efficacy of s.c. melagatran 3 mg/ximelagatran 24 mg twice daily initiated post-operatively (4-12 h after surgery) was comparable to that of the LMWH enoxaparin initiated 12 h before surgery (total VTE incidence, 31.0 and 27.3%, respectively). Rates of severe bleeding were also comparable between treatments (melagatran/ximelagatran = 1.4%; enoxaparin = 1.7%). Treatment with melagatran/ximelagatran was significantly more effective when initiated earlier (4-8 h) rather than later (8-12 h) after surgery (total VTE incidence, 27.5 vs. 35.4%; p = 0.0034). Based on the results of METHRO II and III, the EXPRESS study evaluated the efficacy and bleeding profile of s.c. melagatran 2 mg immediately before surgery, followed by s.c. melagatran 3 mg on the evening of the day of surgery and then ximelagatran 24 mg twice daily. This regimen was significantly more effective than enoxaparin (total VTE incidence, 20.3 vs. 26.6%; p < 0.0004). Excessive bleeding (as judged by the investigator) was more frequent with melagatran/ximelagatran, but rates of fatal bleeding, critical-site bleeding and bleeding requiring re-operation did not differ between the groups. Taken together, the METHRO and EXPRESS studies demonstrate that melagatran/ximelagatran has comparable or superior efficacy to LMWHs in the prevention of VTE in orthopaedic surgery patients, and that the timing and dose of melagatran is important in optimizing the balance of efficacy and bleeding risk.
Topics: Azetidines; Benzylamines; Clinical Trials as Topic; Humans; Orthopedic Procedures; Premedication; Thromboembolism; Treatment Outcome
PubMed: 15812199
DOI: 10.1159/000083079 -
Neonatology 2021Neonatal thrombosis is a frequently encountered complication in a neonatal intensive care unit. Dalteparin can be used to treat thrombosis in newborn infants.
BACKGROUND
Neonatal thrombosis is a frequently encountered complication in a neonatal intensive care unit. Dalteparin can be used to treat thrombosis in newborn infants.
OBJECTIVES
In this study, we evaluate the current recommended starting dose of 129 ± 43 U/kg/24 h, hypothesizing that this dose is too low to reach therapeutic anti-Xa levels.
METHODS
From 2008 until 2017, all infants treated with dalteparin in the University Medical Centre Utrecht were included in this study. In this retrospective cohort study, the correlation between dose and anti-Xa level was observed.
RESULTS
Sixty-six infants were included. The most common thrombus types were catheter-related (29 patients, 44%) and venous sinus thrombosis (28 patients, 43%). The mean dalteparin dose needed for the first adequate anti-Xa level (0.5-1.0 IU/mL) was 297.6 U/kg/12 h. Two infants developed a first bleeding episode under dalteparin therapy; they both had anti-Xa levels in the therapeutic range.
CONCLUSION
The increase of the starting dose of dalteparin will lead to earlier therapeutic levels of anti-Xa in the studied population and appears to be safe. However, this needs to be evaluated in further study.
Topics: Anticoagulants; Dalteparin; Humans; Infant; Infant, Newborn; Retrospective Studies; Thrombosis; Treatment Outcome
PubMed: 33735895
DOI: 10.1159/000513784 -
BMC Musculoskeletal Disorders Jan 2023Tranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of different antithrombotic agents in combination with tranexamic acid for venous thromboembolism prophylaxis and blood management after total knee replacement: a prospective randomized study.
BACKGROUND
Tranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in patients after surgery. The choice of antithrombotic agents for venous thromboembolism (VTE) prevention after TKA is controversial. Therefore, this study aimed to compare the effects of different antithrombotic agents on patients after primary unilateral TKA in the context of applied TXA.
METHODS
A total of 180 patients undergoing primary unilateral TKA from October 2020 to December 2021 were included in this study. All patients were given an intraoperative drip of 60 mg/kg TXA. Thereafter, patients were divided into three groups (n = 60 each). Baseline data were comparable among the three groups. The average follow-up time was 3.02 ± 0.09 months. Group 1 enrolled patients receiving oral rivaroxaban (RA) at 10 mg, Group 2 included patients who received subcutaneous Dalteparin sodium at 2500 IU, while Group 3 included patients taking oral aspirin (ASA) at 100 mg. Patients in all the three groups received treatment once a day for 30 days at 12 h postoperatively. The primary outcomes in this study were post-treatment drainage volume and thrombotic complication rate. The secondary outcomes included hematologic parameters, transfusion rate, intraoperative blood loss, total blood loss (TBL), and bleeding complication rate.
RESULTS
The average drainage volume after treatment was significantly lower in Group 3 than in Group 1 and Group 2 (205.2 ± 69.0 vs 243.4 ± 72.5 vs 295.4 ± 72.5 ml, P < 0.001), and there was a significant difference between Group 1 and Group 2 (243.4 ± 72.5 mL vs 295.4 ± 72.5 mL, P < 0.001). The blood transfusion rate of Group 2 dramatically increased compared with Group 1 and Group 3 (20.0% vs 6.7% vs 5.0%, P = 0.01). The bleeding complication rate in Group 1 apparently increased relative to Group 2 and Group 3 (26.7% vs 10.0% vs 8.3%, P = 0.008). Besides, there was no significant difference in the thrombotic complication rate among the three groups.
CONCLUSION
Under the background of TXA application, ASA, RA, and Dalteparin sodium were all effective on preventing VTE after TKA. In addition, ASA effectively reduced post-treatment Hemoglobin (Hb) loss, drainage volume, TBL, transfusion rate, and bleeding complications compared with RA and Dalteparin sodium.
TRIAL REGISTRATION
The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200060169). Date of Registration: 21/05/2022.
Topics: Humans; Tranexamic Acid; Arthroplasty, Replacement, Knee; Venous Thromboembolism; Fibrinolytic Agents; Antifibrinolytic Agents; Dalteparin; Prospective Studies; Blood Loss, Surgical; Rivaroxaban; Anticoagulants; Postoperative Hemorrhage
PubMed: 36600227
DOI: 10.1186/s12891-022-06117-8 -
Journal of Thrombosis and Haemostasis :... Oct 2011Upper extremity deep vein thrombosis (DVT) can result in fatal pulmonary embolism if not treated. Patients with malignancy may be at particularly high risk. Heparin or...
BACKGROUND
Upper extremity deep vein thrombosis (DVT) can result in fatal pulmonary embolism if not treated. Patients with malignancy may be at particularly high risk. Heparin or low-molecular-weight heparin followed by warfarin has been used as standard treatment for lower extremity DVT. However, a paucity of studies exist reporting the efficacy and safety of these regimens in patients with upper extremity DVT. We studied the effectiveness and safety of treatment with dalteparin sodium followed by warfarin and also dalteparin sodium monotherapy for 3 months in patients with confirmed upper extremity DVT.
METHODS
Consecutive patients with confirmed upper extremity DVT received daily dalteparin sodium for 5-7 days followed by warfarin therapy for 3 months (phase I) or dalteparin sodium monotherapy for 3 months (phase II). The primary outcome measure was the incidence of new symptomatic venous thromboembolism during the 3-month follow-up period. The outcome measure of safety was the incidence of major and minor bleeding.
RESULTS
Of 631 consecutive patients screened, 74 were eligible and 67 enrolled. No patients receiving either phase I (0%; 95% CI, 0-12%) or phase II (0%; 95% CI, 0-9%) therapy had venous thromboembolism on 3-month follow-up. One patient (4%; 95% CI, 0-18%) receiving phase I therapy experienced major bleeding. Five patients died during the follow-up period; none were attributed to pulmonary embolism.
CONCLUSIONS
Patients with upper extremity DVT may be treated safely with either dalteparin sodium followed by warfarin or dalteparin sodium monotherapy for 3 months with a good prognosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Dalteparin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Upper Extremity Deep Vein Thrombosis; Warfarin; Young Adult
PubMed: 21838756
DOI: 10.1111/j.1538-7836.2011.04466.x -
International Archives of Allergy and... 2016Immediate type hypersensitivity reactions due to heparins are rare, and the exact immunologic pathomechanism has not been identified so far. In our 2 case reports, we... (Review)
Review
Immediate type hypersensitivity reactions due to heparins are rare, and the exact immunologic pathomechanism has not been identified so far. In our 2 case reports, we describe first a 50-year-old female who received dalteparin (Fragmin®) and developed signs of an immediate type hypersensitivity reaction. The personal history revealed a previous application of dalteparin (Fragmin®). Evaluation with a skin prick test showed positive results for dalteparin. The second case deals with a 73-year-old female with a suspected immediate type reaction after the administration of dalteparin (Fragmin®). A skin prick test was negative but intracutaneous tests showed a positive reaction to the causative agent. Both cases indicated cross-reactivity reactions for low-molecular-weight heparin (LMWH) but not for unfractioned heparin (UFH) or fondaparinux. In conclusion, our case reports including a review of published cases of immediate type hypersensitivity reactions after the application of heparins illustrate this rare complication. Mostly, the causative agent can be identified with a skin test, which is highly suggestive of an IgE-mediated reaction. Therapeutic alternatives for patients with sensitization to an LMWH are UFH and fondaparinux. Both agents have a small risk of cross-reactivity compared to heparins of the same substance class.
Topics: Aged; Anticoagulants; Cross Reactions; Drug Hypersensitivity; Female; Heparin; Humans; Hypersensitivity, Immediate; Middle Aged; Skin Tests
PubMed: 28049195
DOI: 10.1159/000453525 -
Basic & Clinical Pharmacology &... Oct 2017The primary objective of our study was to evaluate the frequency of suspected heparin-induced thrombocytopenia (HIT) among patients treated with different formulations... (Comparative Study)
Comparative Study
The primary objective of our study was to evaluate the frequency of suspected heparin-induced thrombocytopenia (HIT) among patients treated with different formulations of heparin and investigate the factors that affect the incidence of HIT. This study is an electronic medical record (EMR)-based large-scale retrospective cohort study conducted from 2009 to 2014 in Korea. After hospitalization, patient platelet count was determined before heparin was prescribed, and all platelet count values obtained during hospitalization were extracted. Suspected HIT was estimated by three 4Ts scores (acute thrombocytopenia, timing onset and other possible causes), which when combined yielded a high probability of HIT. Among 6046 patients enrolled in this study, HIT was suspected in 641 cases (10.6%) and a statistically significant increase in HIT incidence rate was observed for three heparins used (p < 0.001). Dalteparin (HR = 0.55, p = 0.036) and enoxaparin (HR = 0.40, p < 0.001) showed a relatively low HIT incidence rate, compared to unfractionated heparin. Majority of suspected HIT cases (76.9 and 66.7%) occurred in days 8-10 and 5-7 of dalteparin and enoxaparin treatments, respectively. Most of the patients medicated with dalteparin were cancer patients; however, no statistically significant relationship was observed between HIT occurrence and cancer. HIT can cause serious complications, making early diagnosis crucial. Clinical practitioners first prescribing heparin should focus on preventing and detecting complications early by conducting frequent, regular platelet counts before and after heparin administration.
Topics: Aged; Anticoagulants; Dalteparin; Drug Compounding; Drug Monitoring; Enoxaparin; Female; Humans; Incidence; Male; Middle Aged; Nadroparin; Platelet Count; Republic of Korea; Retrospective Studies; Risk Factors; Thrombocytopenia; Time Factors
PubMed: 28374942
DOI: 10.1111/bcpt.12791 -
Iranian Journal of Kidney Diseases Jul 2009Dialysis-induced oxidative stress is one of the mechanisms of atherosclerotic changes. Heparin, used in hemodialysis, is an anticoagulant drug with anti-inflammatory and... (Clinical Trial)
Clinical Trial Comparative Study
INTRODUCTION
Dialysis-induced oxidative stress is one of the mechanisms of atherosclerotic changes. Heparin, used in hemodialysis, is an anticoagulant drug with anti-inflammatory and antioxidant effects. This study was planned in order to evaluate the antioxidant effects of heparin and dalteparin (low-molecular weight heparin).
MATERIALS AND METHODS
Twenty-two patients underwent 3 hemodialysis sessions with 48-hour intervals. They underwent hemodialysis with heparin, with a bolus dose of 1000 U followed by 1000 U/h during the procedure. The second hemodialysis was done using hypertonic saline solution instead of heparin, and the third, using dalteparin, 4000 U, infused during hemodialysis. Before and after each dialysis session, we measured serum levels of total blood cholesterol, triglyceride, high- and low-density lipoprotein cholesterols and oxidized low-density lipoprotein cholesterol, in addition to total antioxidant capacity and paraoxonase 1 activity.
RESULTS
Serum concentrations of triglyceride, cholesterol, and oxidized low-density lipoprotein cholesterol, as well as paraoxonase activity and total antioxidant capacity equally increased after the three hemodialysis sessions. Heparin and daltepain increased total antioxidant capacity, but they did not change the ratio of paraoxonase 1 to high-density lipoprotein cholesterol after hemodialysis. No significant differences were found through the study between the two heparin products in their antioxidant activities.
CONCLUSIONS
Regarding these findings and considering higher price and less availability of dalteparin in comparison to conventional heparin, we recommend using conventional heparin during hemodialysis as the anticoagulant-antioxidant agent.
Topics: Adult; Aged; Anticoagulants; Aryldialkylphosphatase; Dalteparin; Drug Costs; Female; Heparin; Humans; Kidney Failure, Chronic; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Thrombosis; Triglycerides; Young Adult
PubMed: 19617666
DOI: No ID Found