Anti-FXa Activity with Intermediate-Dose Thromboprophylaxis in COVID-19.
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SUBMITTER: Rappaport SH
PROVIDER: S-EPMC7737599 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7737584 | biostudies-literature
Project description:ImportanceHospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown.ObjectiveTo evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19.Design, setting, and participantsThe HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US.InterventionsPatients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status.Main outcomes and measuresThe primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data.ResultsOf 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71).Conclusions and relevanceIn this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients.Trial registrationClinicalTrials.gov Identifier: NCT04401293.
| S-EPMC8498934 | biostudies-literature
Project description:IntroductionSome local protocols suggest using intermediate or therapeutic doses of anticoagulants for thromboprophylaxis in hospitalized patients with coronavirus disease 2019 (COVID-19). However, the incidence of bleeding, predictors of major bleeding, or the association between bleeding and mortality remain largely unknown.MethodsWe performed a cohort study of patients hospitalized for COVID-19 that received intermediate or therapeutic doses of anticoagulants from March 25 to July 22, 2020, to identify those at increased risk for major bleeding. We used bivariate and multivariable logistic regression to explore the risk factors associated with major bleeding.ResultsDuring the study period, 1965 patients were enrolled. Of them, 1347 (69%) received intermediate- and 618 (31%) therapeutic-dose anticoagulation, with a median duration of 12 days in both groups. During the hospital stay, 112 patients (5.7%) developed major bleeding and 132 (6.7%) had non-major bleeding. The 30-day all-cause mortality rate for major bleeding was 45% (95% confidence interval [CI]: 36%-54%) and for non-major bleeding 32% (95% CI: 24%-40%). Multivariable analysis showed increased risk for in-hospital major bleeding associated with D-dimer levels >10 times the upper normal range (hazard ratio [HR], 2.23; 95% CI, 1.38-3.59), ferritin levels >500 ng/ml (HR, 2.01; 95% CI, 1.02-3.95), critical illness (HR, 1.91; 95% CI, 1.14-3.18), and therapeutic-intensity anticoagulation (HR, 1.43; 95% CI, 1.01-1.97).ConclusionsAmong patients hospitalized with COVID-19 receiving intermediate- or therapeutic-intensity anticoagulation, a major bleeding event occurred in 5.7%. Use of therapeutic-intensity anticoagulation, critical illness, and elevated D-dimer or ferritin levels at admission were associated with increased risk for major bleeding.
| S-EPMC8237051 | biostudies-literature
Project description:Our objective was to assess the incidence of drug bioaccumulation in critically ill COVID-19 patients with AKI receiving intermediate dose nadroparin for thrombosis prophylaxis. We conducted a Prospective cohort study of critically ill COVID-19 patients. In patients on intermediate dose nadroparin (5700 IU once daily) we assessed the incidence of bioaccumulation (trough anti-Xa level > 0.2 IU/mL) stratified according to presence of AKI. We quantified this association using multilevel analyses. To assess robustness of our observations, we explored the association between AKI and anti-Xa activity in patients receiving high dose nadroparin (> 5700 IU). 108 patients received intermediate dose nadroparin, of whom 24 had AKI during 36 anti-Xa measurements. One patient with AKI (4.2% [95%CI 0.1-21%]) and 1 without (1.2% [95%CI 0.03-6.5%]) developed bioaccumulation (p = 0.39). Development of AKI was associated with a mean increase of 0.04 (95%CI 0.02-0.05) IU/ml anti-Xa activity. There was no statistically significant association between anti-Xa activity and AKI in 51 patients on high dose nadroparin. There were four major bleeding events, all in patients on high dose nadroparin. In conclusion, Bioaccumulation of an intermediate dose nadroparin did not occur to a significant extent in critically ill patients with COVID-19 complicated by AKI. Dose adjustment in AKI may be unnecessary.
| S-EPMC9579123 | biostudies-literature
Project description:ObjectivesTo compare mortality of hospitalized COVID-19 patients under two low-molecular weight heparin (LMWH) thromboprophylaxis strategies: standard dose and variable dose (standard dose increased to intermediate dose in the presence of laboratory abnormalities indicating an increased thrombosis risk).Study design and settingTarget trial emulation using observational data from 2,613 adults admitted with a COVID-19 diagnosis in Madrid, Spain between March 16 and April 15, 2020.ResultsA total of 1,284 patients were eligible. Among 503 patients without increased baseline thrombotic risk, 28-day mortality risk (95% confidence interval [CI]) was 9.0% (6.6, 11.7) under the standard dose strategy and 5.6% (3.3, 8.3) under the variable dose strategy; risk difference 3.4% (95% CI: -0.24, 6.9); mortality hazard ratio 1.61 (95% CI: 0.97, 2.89). Among 781 patients with increased baseline thrombotic risk, the 28-day mortality risk was 25.8% (22.7, 29.0) under the standard dose strategy and 18.1% (9.3, 28.9) under the intermediate dose strategy; risk difference 7.7% (95% CI: -3.5, 17.2); mortality hazard ratio 1.45 (95% CI: 0.81, 3.17). Major bleeding and LMWH-induced coagulopathy were rare under all strategies.ConclusionEscalating anticoagulation intensity after signs of thrombosis risk may increase the survival of hospitalized COVID-19 patients. However, effect estimates were imprecise and additional studies are warranted.
| S-EPMC9385269 | biostudies-literature
Project description: Not available
| S-EPMC7557260 | biostudies-literature
Project description:BackgroundHospitalized COVID-19 patients are at high risk of venous thromboembolism (VTE). Standard doses of anticoagulant prophylaxis may not be sufficiently effective for the prevention of VTE. The objective of this systematic-review and meta-analysis was to compare the efficacy and safety of high-dose versus low-dose thromboprophylaxis in hospitalized patients with COVID-19.Material and methodsMEDLINE and EMBASE were searched up to October 2021 for randomized clinical trials (RCTs) comparing high-dose with low-dose thromboprophylaxis in hospitalized adult patients with COVID-19. The primary efficacy outcome was the occurrence of VTE and the primary safety outcome was major bleeding.ResultsA total of 5470 patients from 9 RCTs were included. Four trials included critically ill patients, four non-critically ill patients, and one included both. VTE occurred in 2.9% of patients on high-dose and in 5.7% of patients on low-dose thromboprophylaxis (relative risk [RR] 0.53; 95% confidence intervals [CIs], 0.41-0.69; I2 = 0%; number needed to treat for an additional beneficial outcome, 22). Major bleeding occurred in 2.5% and 1.4% of patients, respectively (RR 1.78; 95% CI, 1.20-2.66; I2 = 0%; number needed to treat for an additional harmful outcome, 100). All-cause mortality did not differ between groups (RR 0.97; 95% CI, 0.75-1.26; I2 = 47%). The risk of VTE was significantly reduced by high-dose thromboprophylaxis in non-critically ill (RR 0.54; 95% CI, 0.35-0.86; I2 = 0%), but not in critically ill patients (RR 0.69; 95% CI, 0.39-1.21; I2 = 36%).DiscussionIn hospitalized patients with COVID-19, high-dose thromboprophylaxis is more effective than low-dose for the prevention of VTE but increases the risk of major bleeding.
| S-EPMC9244067 | biostudies-literature
Project description:Background Thromboembolism remains a detrimental complication of novel coronavirus disease (COVID-19) despite the use of prophylactic doses of anticoagulation Objectives This study aimed to compare different thromboprophylaxis strategies in COVID-19 patients Methods We conducted a systematic database search until June 30, 2022. Eligible studies were randomized (RCTs) and nonrandomized studies that compared prophylactic to intermediate or therapeutic doses of anticoagulation in adult patients with COVID-19, admitted to general wards or intensive care unit (ICU). Primary outcomes were mortality, thromboembolism, and bleeding events. Data are analyzed separately in RCTs and non-RCTs and in ICU and non-ICU patients. Results. We identified 682 studies and included 53 eligible studies. Therapeutic anticoagulation showed no mortality benefit over prophylactic anticoagulation in four RCTs (odds ratio [OR] = 0.67, 95% confidence interval [CI], 0.18-2.54). Therapeutic anticoagulation didn't improve mortality in ICU or non-ICU patients. Risk of thromboembolism was significantly lower among non-ICU patients who received enhanced (therapeutic/intermediate) anticoagulation (OR = 0.21, 95% CI, 0.06-0.74). Two additional RCTs (Multiplatform Trial and HEP-COVID), not included in quantitative meta-analysis, analyzed non-ICU patients, and reported a similar benefit with therapeutic-dose anticoagulation. Therapeutic anticoagulation was associated with a significantly higher risk of bleeding events among non-randomized studies (OR = 3.45, 95% CI, 2.32-5.13). Among RCTs, although patients who received therapeutic-dose anticoagulation had higher numbers of bleeding events, these differences were not statistically significant. Studies comparing prophylactic and intermediate-dose anticoagulation showed no differences in primary outcomes. Conclusion There is a lack of mortality benefit with therapeutic-dose over prophylactic-dose anticoagulation in ICU and non-ICU COVID-19 patients. Therapeutic anticoagulation significantly decreased risk of thromboembolism risk in some of the available RCTs, especially among non-ICU patients. This potential benefit, however, may be counter balanced by higher risk of bleeding. Individualized assessment of patient's bleeding risk will ultimately impact the true clinical benefit of anticoagulation in each patient. Finally, we found no mortality or morbidity benefit with intermediate-dose anticoagulation.
| S-EPMC9581586 | biostudies-literature
Project description:The Corona Virus Disease-2019 (COVID-19) pandemic is associated with a very high incidence of thrombotic complications. The exact mechanisms for this excess risk for clots have not been elucidated although one of the often-quoted pathophysiological entity is immunothrombosis. Recognition of thrombotic complications early on in this pandemic led to an over-explosion of studies which looked at the benefits of anticoagulation to mitigate this risk. In this review, we examine the rationale for thromboprophylaxis in COVID-19 with particular reference to dosing and discuss what may guide the decision-making process to consider anticoagulation. In addition, we explore the rationale for thrombosis prevention measures in special populations including outpatient setting, pregnant females, children, those with high body mass index and those on extracorporeal membrane oxygenation.
| S-EPMC8299150 | biostudies-literature
Project description: Not available
| S-EPMC9452396 | biostudies-literature