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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 -
Journal of Gynecologic Oncology Jan 2020
Topics: Anticoagulants; Dalteparin; Female; Humans; Neoplasm Recurrence, Local; Rivaroxaban; Venous Thromboembolism
PubMed: 31833262
DOI: 10.3802/jgo.2020.31.e40 -
Journal of Diabetes and Metabolic... Dec 2022Coronavirus Disease 2019 (COVID-19) is a recent public health issue worldwide. Also, diabetes is a frequent condition with high mortality. There is a strong relationship... (Review)
Review
Coronavirus Disease 2019 (COVID-19) is a recent public health issue worldwide. Also, diabetes is a frequent condition with high mortality. There is a strong relationship between COVID-19 and diabetes. This article analyses the intricate relationship between COVID-19 and hepcidin. Hepcidin increases in aged non-insulin diabetic patients. Hepcidin is the last target treatment of several medications commonly used. Viral diseases, especially SARS-CoV19, can activate the hepcidin pathway leading to an elevation in the iron load. This increased iron is released into the bloodstream and results in cell death through ferroptosis, like free iron. Excess iron has pro-coagulative and toxic effects. Hepcidin overexpression and iron overload are associated with COVID-19 infection and can be considered potential targets for treatment. Several studies have shown dalteparin (anti-Hepcidin) could improve the symptoms of COVID-19 in diabetics by appropriately modulating and decreasing oxidative stress and inflammation. This finding can be leading to enhancing the existing knowledge about Therapeutic measures for reducing Covid-19 impairments in diabetics and is suggested as a possible therapeutic agent in diabetes.
PubMed: 35812243
DOI: 10.1007/s40200-022-01053-9 -
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 -
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 -
Comparative Effectiveness of Enoxaparin vs Dalteparin for Thromboprophylaxis After Traumatic Injury.Chest Jan 2018Enoxaparin 30 mg twice daily and dalteparin 5,000 units once daily are two common low-molecular-weight heparin (LMWH) thromboprophylaxis regimens used in the trauma... (Comparative Study)
Comparative Study
BACKGROUND
Enoxaparin 30 mg twice daily and dalteparin 5,000 units once daily are two common low-molecular-weight heparin (LMWH) thromboprophylaxis regimens used in the trauma population. Pharmacodynamic studies suggest that enoxaparin provides more potent anticoagulation than does dalteparin.
METHODS
In 2009, our institution switched its formulary LMWH from enoxaparin to dalteparin followed by a switch back to enoxaparin in 2013. Using a difference in differences design, we contrasted the change in the VTE rate accompanying the LMWH switch with the change in a control group of trauma patients given unfractionated heparin (UFH) during the same period.
RESULTS
The study included 5,880 patients: enoxaparin period (enoxaparin, n = 2,371; UFH, n = 1,539) vs the dalteparin period (dalteparin, n = 1,046; UFH, n = 924). The VTE rate was unchanged in the LMWH group: 3.3/1000 days in the enoxaparin period vs 3.8/1000 days in the dalteparin period: rate ratio (RR), 1.16; 95% CI 0.74-1.81. The rate was also unchanged in the UFH control subjects: 5.7/1,000 days in the enoxaparin period vs 5.2/1,000 days in the dalteparin period: RR, 0.92; 95% CI, 0.61-1.38. After confounding adjustment, the ratio of the change in VTE rate between the LMWH and UFH groups was similar: RR, 1.06; 95% CI 0.71-2.00. A secondary analysis excluding patients with delayed or interrupted prophylaxis (or both) altered this estimate nonsignificantly in favor of enoxaparin: RR, 2.39; 95% CI, 0.80-7.09.
CONCLUSIONS
Our results suggest that dalteparin has an effectiveness similar to that of enoxaparin in real-world trauma patients. Future research should investigate how the timing and consistency of prophylaxis affects LMWH effectiveness.
Topics: Adolescent; Adult; Aged; Case-Control Studies; Comparative Effectiveness Research; Dalteparin; Drug Administration Schedule; Drug Substitution; Enoxaparin; Fibrinolytic Agents; Humans; Middle Aged; Trauma Centers; Treatment Outcome; Venous Thromboembolism; Wounds and Injuries; Young Adult
PubMed: 28823757
DOI: 10.1016/j.chest.2017.08.008 -
Journal of Gynecologic Oncology Jan 2020Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous... (Comparative Study)
Comparative Study
OBJECTIVES
Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous thromboembolism (VTE) have previously been performed. However, gynecologic cancers accounted for approximately 10% of the study populations. We compared the outcomes of patients with primary gynecological cancers who were treated for cancer-associated VTE with either rivaroxaban or dalteparin.
METHODS
The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality.
RESULTS
During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%).
CONCLUSION
In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.
Topics: Aged; Dalteparin; Factor Xa Inhibitors; Female; Genital Neoplasms, Female; Hemorrhage; Humans; Middle Aged; Proportional Hazards Models; Republic of Korea; Rivaroxaban; Venous Thromboembolism
PubMed: 31789000
DOI: 10.3802/jgo.2020.31.e10 -
Cellular Physiology and Biochemistry :... 2017Venous thromboembolism (VTE) is the most common complication after major joint surgery. VTE can easily develop into pulmonary embolism (PE), leading to cardiopulmonary... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Venous thromboembolism (VTE) is the most common complication after major joint surgery. VTE can easily develop into pulmonary embolism (PE), leading to cardiopulmonary dysfunction or sudden death. We aimed to comprehensively analyse the thromboprophylactic drugs that are used to prevent thrombosis and reduce bleeding risk.
METHODS
We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that evaluated the use of thromboprophylaxis after major joint surgery. The major outcomes were the numbers of all-cause VTE and bleeding events, and the secondary outcomes were major VTE and major bleeding/clinically relevant non-major bleeding events. A random-effects network meta-analysis was used to assess the effectiveness and tolerability of each anticoagulant after major joint surgery.
RESULTS
We included 104 trials that assessed 110,643 patients in our meta-analysis. The cluster ranking of major outcomes indicated that FXI-ASO, ardeparin, aspirin, and apixaban were ideal for preventing all-cause VTE and avoiding all bleeding events. Nadroparin, recombinant hirudin, and rivaroxaban effectively inhibited VTE but were associated with a high risk of bleeding. For secondary outcomes, we found that betrixaban, dalteparin, warfarin, and eribaxaban were ideal for preventing major VTE and reducing major bleeding, while rivaroxaban effectively inhibited major VTE but was associated with a high risk of major/clinically relevant non-major bleeding. A sensitivity analysis showed that the effect of apixaban was more robust for major outcomes, while aspirin was more robust for preventing all-cause bleeding events. In secondary outcomes, the effect of warfarin was more robust, while apixaban was still considered an ideal treatment to inhibit major VTE and bleeding events.
CONCLUSION
Our study indicates that FXI-ASO, ardeparin, aspirin, and apixaban are ideal for preventing all-cause VTE and reducing all bleeding events, among which apixaban is the most reliable. Betrixaban, dalteparin, warfarin, and eribaxaban are ideal for preventing major VTE and reducing major/clinically relevant non-major bleeding events, among which warfarin is the most reliable.
Topics: Anticoagulants; Aspirin; Databases, Factual; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Joint Diseases; Odds Ratio; Postoperative Complications; Pyrazoles; Pyridones; Venous Thromboembolism
PubMed: 28793291
DOI: 10.1159/000479840 -
The European Respiratory Journal Feb 2020In cancer patients, current guidance suggests similar treatment for incidental and symptomatic venous thromboembolism (VTE), mainly based on retrospective data. We aimed... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
In cancer patients, current guidance suggests similar treatment for incidental and symptomatic venous thromboembolism (VTE), mainly based on retrospective data. We aimed to evaluate anticoagulant therapy in cancer patients with incidental and symptomatic VTE.
METHODS
The Hokusai VTE Cancer Study was a randomised controlled trial comparing edoxaban with dalteparin for cancer-associated VTE. The primary outcome was the composite of first recurrent VTE or major bleeding. Secondary outcomes included major bleeding, recurrent VTE and mortality. Outcomes in patients with incidental and symptomatic VTE were evaluated during the 12-month study period.
RESULTS
331 patients with incidental VTE and 679 patients with symptomatic VTE were enrolled, of whom the index event was confirmed by an independent radiologist. Median durations of anticoagulant treatment were 195 and 189 days, respectively. In patients with incidental VTE, the primary outcome occurred in 12.7% of patients, major bleeding in 6.6% of patients and recurrent VTE in 7.9% of patients. Out of the 26 VTE recurrences in patients with incidental VTE, five (31%) were incidental, seven (44%) were symptomatic and four (25%) were deaths for which pulmonary embolism could not be ruled out. In patients with symptomatic VTE, the primary outcome occurred in 13.8% of patients, major bleeding in 4.9% of patients and recurrent VTE in 10.9% of patients. All-cause mortality was similar in both groups.
CONCLUSION
Clinical adverse outcomes are substantial in both cancer patients with incidental and symptomatic VTE, supporting current guideline recommendations that suggest treating incidental VTE in the same manner as symptomatic VTE.
Topics: Anticoagulants; Dalteparin; Humans; Neoplasm Recurrence, Local; Retrospective Studies; Venous Thromboembolism
PubMed: 31727694
DOI: 10.1183/13993003.01697-2019 -
Journal of Critical Care Dec 2020The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on... (Observational Study)
Observational Study
PURPOSE
The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients.
MATERIAL AND METHODS
We conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75-100 IU/kg subcutaneously).
RESULTS
Five patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity.
CONCLUSIONS
Patients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties.
Topics: Adult; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Critical Illness; Dalteparin; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Risk; Thrombelastography; Venous Thromboembolism; COVID-19 Drug Treatment
PubMed: 32920503
DOI: 10.1016/j.jcrc.2020.08.026