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1.
Pediatrics ; 2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1817537

ABSTRACT

BACKGROUND: Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for COVID-19 is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19 including primary respiratory infection and multisystem inflammatory syndrome in children (MIS-C). METHODS: We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg/dose; max: 60 mg; adjusted to a target anti-Xa activity: 0.20-0.49 IU/ml) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: (1) cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; (2) enoxaparin dose-requirements; and (3) cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by patient age (±12 years) and clinical presentation. RESULTS: Forty children were enrolled and 38 met criteria for analyses. No participants experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P=0.51) but greater for participants with MIS-C (0.52 [0.5-0.61] mg/kg) as compared to primary COVID-19 (0.48 [0.39-0.51] mg/kg, P=0.010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention, including one death. CONCLUSIONS: Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.

2.
Lancet ; 399(10319): 50-59, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1815305

ABSTRACT

BACKGROUND: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. METHODS: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. FINDINGS: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. INTERPRETATION: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. FUNDING: Bayer.


Subject(s)
Aftercare , Blood Coagulation/drug effects , COVID-19/complications , Factor Xa Inhibitors/pharmacology , Factor Xa Inhibitors/therapeutic use , Rivaroxaban/pharmacology , Rivaroxaban/therapeutic use , Venous Thromboembolism/prevention & control , Adult , Aged , COVID-19/drug therapy , Female , Heparin/administration & dosage , Heparin/therapeutic use , Hospitalization , Humans , Male , Middle Aged , Patient Discharge , Treatment Outcome
4.
Lancet ; 399(10320): 118-119, 2022 01 08.
Article in English | MEDLINE | ID: covidwho-1612113
7.
J Thromb Thrombolysis ; 52(4): 1032-1035, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1525576

ABSTRACT

There is a need to discriminate which COVID-19 inpatients are at higher risk for venous thromboembolism (VTE) to inform prophylaxis strategies. The IMPROVE-DD VTE risk assessment model (RAM) has previously demonstrated good discrimination in non-COVID populations. We aimed to externally validate the IMPROVE-DD VTE RAM in medical patients hospitalized with COVID-19. This retrospective cohort study evaluated the IMPROVE-DD VTE RAM in adult patients with COVID-19 admitted to one of thirteen Northwell Health hospitals in the New York metropolitan area between March 1, 2020 and April 27, 2020. VTE was defined as new-onset symptomatic deep venous thrombosis or pulmonary embolism. To assess the predictive value of the RAM, the receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Of 9407 patients who met study criteria, 274 patients developed VTE with a prevalence of 2.91%. The VTE rate was 0.41% for IMPROVE-DD score 0-1 (low risk), 1.21% for score 2-3 (moderate risk), and 5.30% for score ≥ 4 (high risk). Approximately 45.7% of patients were classified as high VTE risk, 33.3% moderate risk, and 21.0% low risk. Discrimination of low versus moderate-high VTE risk demonstrated sensitivity 0.971, specificity 0.215, PPV 0.036, and NPV 0.996. ROC AUC was 0.703. In this external validation study, the IMPROVE-DD VTE RAM demonstrated very good discrimination to identify hospitalized COVID-19 patients at low, moderate, and high VTE risk.


Subject(s)
COVID-19 , Risk Assessment , Venous Thromboembolism , COVID-19/complications , Humans , Inpatients , New York City , Retrospective Studies , Risk Factors , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology
8.
J Clin Med ; 10(22)2021 Nov 18.
Article in English | MEDLINE | ID: covidwho-1524043

ABSTRACT

BACKGROUND: We aimed to investigate the potential beneficial effect of immunomodulation therapy on the thromboembolic risk in hospitalized COVID-19 patients. METHODS: We searched PubMed and Scopus for randomized trials reporting the outcomes of venous thromboembolism (VTE), ischemic stroke or systemic embolism, myocardial infarction, any thromboembolic event, and all-cause mortality in COVID-19 patients treated with immunomodulatory agents. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using the Mantel-Haenszel random effects method. RESULTS: Among 8499 patients hospitalized with COVID-19, 4638 were treated with an immunomodulatory agent, 3861-with usual care only. Among the patients prescribed immunomodulatory agents, there were 1.77 VTEs per 100 patient-months compared to 2.30 among those treated with usual care (OR: 0.84, 95% CI: 0.61-1.16; I2: 0%). Among the patients who received an interleukin 6 (IL-6) antagonist, VTEs were reported in 12 among the 1075 patients compared to 20 among the 848 receiving the usual care (OR: 0.52, 95% CI: 0.22-1.20; I2: 6%). Immunomodulators as an add-on to usual care did not reduce the risk of stroke or systemic embolism (OR: 1.10, 95% CI: 0.50-2.40; I2: 0%) or of myocardial infarction (OR: 1.06, 95% CI: 0.47-2.39; I2: 0%) and there was a nonsignificant reduction in any thromboembolic event (OR: 0.86, 95% CI: 0.65-1.14; I2: 0%). CONCLUSIONS: We did not identify a statistically significant effect of immunomodulation on prevention of thromboembolic events in COVID-19. However, given the large effect estimate for VTE prevention, especially in the patients treated with IL-6 antagonists, we cannot exclude a potential effect of immunomodulation.

9.
Non-conventional in English | [Unspecified Source], Grey literature | ID: grc-750560
10.
JAMA Intern Med ; 181(12): 1612-1620, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1453495

ABSTRACT

Importance: Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. Objective: To 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 Participants: The 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. Interventions: Patients 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 Measures: The 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. Results: Of 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 Relevance: In 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 Registration: ClinicalTrials.gov Identifier: NCT04401293.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/diagnosis , Enoxaparin/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Heparin/administration & dosage , Hospital Mortality , Inpatients , Venous Thromboembolism/prevention & control , Adult , Aged , COVID-19/blood , COVID-19/therapy , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Humans , Intensive Care Units , Male , SARS-CoV-2 , Treatment Outcome
11.
Am Heart J ; 242: 115-122, 2021 12.
Article in English | MEDLINE | ID: covidwho-1392113

ABSTRACT

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.


Subject(s)
COVID-19/complications , Factor Xa Inhibitors/administration & dosage , Rivaroxaban/administration & dosage , Thrombosis/prevention & control , Adult , Brazil , Drug Administration Schedule , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Humans , Male , Prospective Studies , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Rivaroxaban/adverse effects , Thromboembolism/etiology , Thromboembolism/prevention & control , Thrombosis/etiology , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
12.
Res Pract Thromb Haemost ; 5(5): e12520, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1355899

ABSTRACT

INTRODUCTION: Pulmonary embolism (PE) has not been accounted for as a cause of death contributing to cause-specific mortality in global reports. METHODS: We analyzed global PE-related mortality by focusing on the latest year available for each member state in the World Health Organization (WHO) mortality database, which provides age-sex-specific aggregated mortality data transmitted by national authorities for each underlying cause of death. PE-related deaths were defined by International Classification of Diseases, Tenth Revision codes for acute PE or nonfatal manifestations of venous thromboembolism (VTE). The 2001 WHO standard population served for standardization. RESULTS: We obtained data from 123 countries covering a total population of 2 602 561 422. Overall, 50 (40.6%) were European, 39 (31.7%) American, 13 (10.6%) Eastern Mediterranean, 13 (10.6%) Western Pacific, 3 (2.4%) Southeast Asian, and 2 (1.6%) African. Of 116 countries classifiable according to population income, 57 (49.1%) were high income, 42 (36.2%) upper-middle income, 14 (12.1%) lower-middle income, and 3 (2.6%) low income. A total of 18 726 382 deaths were recorded, of which 86 930 (0.46%) were attributed to PE. PE-related mortality rate increased with age in most countries. The reporting of PE-related deaths was heterogeneous, with an age-standardized mortality rate ranging from 0 to 24 deaths per 100 000 population-years. Income status only partially explained this heterogeneity. CONCLUSIONS: Reporting of PE-related mortality in official national vital registration was characterized by extreme heterogeneity across countries. These findings mandate enhanced efforts toward systematic and uniform coverage of PE-related mortality and provides a case for full recognition of PE and VTE as a primary cause of death.

13.
Blood ; 136(Supplement 1):33-34, 2020.
Article in English | PMC | ID: covidwho-1339052

ABSTRACT

IntroductionThromboembolic outcomes have emerged as an important issue in sick hospitalized patients with COVID-19. Multiple pathogenetic mechanisms for thrombosis have been implicated, including endothelial dysfunction, increased von Willebrand factor (vWF), interleukin-6 release, and activation of/interaction between macrophages, monocytes, endothelial cells, platelets and lymphocytes. The actual rate of arterial and venous thromboembolic events (ATE and VTE) in hospitalized patients with COVID-19, especially in the immediate post-hospital discharge period, has not been fully elucidated, with most of the data derived from retrospective studies with small sample sizes.MethodsAgainst this background, we have designed and implemented an ongoing prospective registry (CORE-19) consisting of 11,249 consecutive hospitalized patients with COVID-19 from March 1st 2020 through May 31st 2020 using data derived from the Northwell Health System and the COVID-19 Research Consortium to study through 90-days post-discharge the rate of VTE and ATE, major bleeding, all-cause mortality, and other complications. We are capturing data of interest including demographic characteristics, co-morbidities, relevant medications, hospital setting, in-hospital treatment, thromboprophylaxis usage, key laboratory parameters, and 90-day thromboembolic and other key outcomes. A unified data repository (datamart) of hospitalized COVID-19 patients across multiple datasets from electronic health records, health informatics exchange, a dedicated radiology database, and a standardized data collection tool in REDCap, that includes telephonic calls up to 90 days post-discharge, is being implemented. A common data model (CDM) is utilized to ensure semantic interoperability between data originating from disparate sources. Northwell Health protocols stipulate the use of post-discharge low-molecular weight heparin, direct oral anticoagulants, or baby aspirin in hospitalized COVID-19 patients with high thrombotic risk features.ResultsOur cohort as of August 7, 2020 consists of complete follow up in 4,100 patients with a mean age of 61.0 years (SD: 17.0) with 54.7% males (Table 1). Preliminary data show an all-cause mortality rate of 4.29%, an overall thromboembolic rate of 3.51% (2.41% VTE and 1.10% ATE), a major bleeding rate of 1.61%, and a rehospitalization rate of 12.85%. Of patients with either DVT or PE post-discharge, 13.43% (9/67) died. The full dataset, including risk factors, comorbidities, key in-hospital and post-discharge medications including anticoagulant and antiplatelet agents, will be available at the time of presentation to the ASH congress.ConclusionOur ongoing registry is a large prospective study evaluating the rate of overall thromboembolic complications and all-cause mortality in hospitalized COVID-19 patients through 90 days post discharge. Current rates of thromboembolic events signify the importance of post-discharge surveillance and, potentially, post-discharge extended thromboprophylaxis, in this acutely ill medical population.

14.
Thromb Haemost ; 121(8): 992-1007, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1320246

ABSTRACT

BACKGROUND: One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. MANAGEMENT: Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. CURRENT ISSUES: The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. PERSPECTIVES: There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). CONCLUSION: The "PDA strategy" integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Public Health , COVID-19/diagnosis , COVID-19 Testing/methods , COVID-19 Vaccines/therapeutic use , Disease Management , Humans , Immunization Programs/methods , Pandemics/prevention & control , Public Health/methods , Risk Assessment , SARS-CoV-2/isolation & purification
15.
Res Pract Thromb Haemost ; 5(5): e12547, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1287399
16.
TH Open ; 5(2): e211-e219, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1284749

ABSTRACT

Introduction Severe novel corona virus disease 2019 (COVID-19) causes dysregulation of the coagulation system with arterial and venous thromboembolism (VTE). We hypothesize that validated VTE risk scores would have prognostic ability in this population. Methods Retrospective observational cohort with severe COVID-19 performed in NorthShore University Health System. Patients were >18 years of age and met criteria for inpatient or intensive care unit (ICU) care. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) and Caprini scores were calculated and patients were stratified. Results This study includes 184 patients, mostly men (63.6%), Caucasian (54.3%), 63 years old (interquartile range [IQR]: 24-101), and 57.1% of them required ICU care. Twenty-seven (14.7%) thrombotic events occurred: 12 (6.5%) cases of disseminated intravascular coagulation (DIC), 9 (4.9%) of pulmonary embolism, 5 (2.7%) of deep vein thrombosis, and 1 (0.5%) stroke. Among them, 86 patients (46.7%) died, 95 (51.6%) were discharged, and 3 (1.6%) were still hospitalized. "Moderate risk for VTE" and "High risk for VTE" by IMPROVE score had significant mortality association: (hazard ratio [HR]: 5.68; 95% confidence interval [CI]: 2.93-11.03; p < 0.001) and (HR = 6.22; 95% CI: 3.04-12.71; p < 0.001), respectively, with 87% sensitivity and 63% specificity (area under the curve [AUC] = 0.752, p < 0.001). "High Risk for VTE" by Caprini score had significant mortality association (HR = 17.6; 95% CI: 5.56-55.96; p < 0.001) with 96% sensitivity and 55% specificity (AUC = 0.843, p < 0.001). Both scores were associated with thrombotic events when classified as "High risk for VTE" by IMPROVE (HR = 6.50; 95% CI: 2.72-15.53; p < 0.001) and Caprini scores (HR = 11.507; 95% CI: 2.697-49.104; p = 0.001). Conclusion The IMPROVE and Caprini risk scores were independent predictors of mortality and thrombotic events in severe COVID-19. With larger validation, this can be useful prognostic information.

17.
Blood ; 137(20): 2838-2847, 2021 05 20.
Article in English | MEDLINE | ID: covidwho-1236540

ABSTRACT

Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients. Whether the risk extends postdischarge has been controversial. Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020. We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes. Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged. Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM). Principal safety outcome was major bleeding (MB). Among 4906 patients (53.7% male), mean age was 61.7 years. Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%). Postdischarge thromboprophylaxis was prescribed in 13.2%. VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%. Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17). Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81). Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization. Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk. Postdischarge anticoagulation reduced risk by 46%.


Subject(s)
COVID-19/complications , Thromboembolism/epidemiology , Thromboembolism/etiology , Aged , Anticoagulants/therapeutic use , Female , Humans , Male , Middle Aged , Patient Discharge , Registries , Risk Factors , SARS-CoV-2 , Thromboembolism/prevention & control
18.
J Womens Health (Larchmt) ; 30(4): 492-501, 2021 04.
Article in English | MEDLINE | ID: covidwho-1196965

ABSTRACT

Background: Smaller studies suggest lower morbidity and mortality associated with coronavirus disease 2019 (COVID-19) in women. Our aim is to assess the impact of female sex on outcomes in a large cohort of patients hospitalized with COVID-19. Materials and Methods: This is a retrospective observational cohort study of 10,630 adult patients hospitalized with a confirmed COVID-19 polymerase chain reaction between March 1, 2020 and April 27, 2020, with follow-up conducted through June 4, 2020. Logistic regression was used to examine the relationship between sex and the primary outcomes, including length of stay, admission to intensive care unit (ICU), need for mechanical ventilation, pressor requirement, and all-cause mortality as well as major adverse events and in-hospital COVID-19 treatments. Results: In the multivariable analysis, women had 27% lower odds of in-hospital mortality (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.66-0.81; p < 0.001), 24% lower odds of ICU admission (OR = 0.76, 95% CI 0.69-0.84; p < 0.001), 26% lower odds of mechanical ventilation (OR = 0.74, 95% CI 0.66-0.82; p < 0.001), and 25% lower odds of vasopressor requirement (OR = 0.75, 95% CI 0.67-0.84; p < 0.001). Women had 34% less odds of having acute cardiac injury (OR = 0.66, 95% CI 0.59-0.74; p < 0.001; n = 7,289), 16% less odds of acute kidney injury (OR = 0.84, 95% CI 0.76-0.92; p < 0.001; n = 9,840), and 27% less odds of venous thromboembolism (OR = 0.73, 95% CI 0.56-0.96; p < 0.02; c-statistic 0.85, n = 9,407). Conclusions: Female sex is associated with lower odds of in-hospital outcomes, major adverse events, and all-cause mortality. There may be protective mechanisms inherent to female sex, which explain differences in COVID-19 outcomes.


Subject(s)
COVID-19/therapy , Hospital Mortality , Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/epidemiology , Cohort Studies , Female , Humans , Male , Middle Aged , New York/epidemiology , Pandemics , Retrospective Studies , SARS-CoV-2 , Sex Distribution , Sex Factors , Treatment Outcome , Young Adult
19.
Blood ; 137(20): 2838-2847, 2021 05 20.
Article in English | MEDLINE | ID: covidwho-1172063

ABSTRACT

Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients. Whether the risk extends postdischarge has been controversial. Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020. We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes. Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged. Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM). Principal safety outcome was major bleeding (MB). Among 4906 patients (53.7% male), mean age was 61.7 years. Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%). Postdischarge thromboprophylaxis was prescribed in 13.2%. VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%. Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17). Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81). Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization. Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk. Postdischarge anticoagulation reduced risk by 46%.


Subject(s)
COVID-19/complications , Thromboembolism/epidemiology , Thromboembolism/etiology , Aged , Anticoagulants/therapeutic use , Female , Humans , Male , Middle Aged , Patient Discharge , Registries , Risk Factors , SARS-CoV-2 , Thromboembolism/prevention & control
20.
Thromb Haemost ; 121(12): 1684-1695, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1171416

ABSTRACT

Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment. Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4 × upper limit of normal (ULN) or sepsis-induced coagulopathy score ≥4. Subjects are randomized to enoxaparin 1 mg/kg subcutaneous (SQ)/two times a day (BID) (creatinine clearance [CrCl] ≥ 30 mL/min) or 0.5 mg/kg (CrCl 15-30 mL/min) versus local institutional prophylactic regimens including (1) UFH up to 22,500 IU (international unit) daily (divided BID or three times a day), (2) enoxaparin 30 and 40 mg SQ QD (once daily) or BID, or (3) dalteparin 2,500 IU or 5,000 IU QD. The principal safety outcome is major bleeding. Events are adjudicated locally. Based on expected 40% relative risk reduction with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power. Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4 × ULN, stratification by intensive care unit (ICU) versus non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Enoxaparin/administration & dosage , Thromboembolism/drug therapy , Anticoagulants/adverse effects , COVID-19/complications , COVID-19/diagnosis , Clinical Trials, Phase III as Topic , Enoxaparin/adverse effects , Humans , Pragmatic Clinical Trials as Topic , Prospective Studies , Risk Assessment , Risk Factors , Thromboembolism/diagnosis , Thromboembolism/etiology , Time Factors , Treatment Outcome , United States , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
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