Abstract
Background
We aimed to identify the prevalence and predictors of venous thromboembolism (VTE) or mortality in hospitalized coronavirus disease 2019 (COVID-19) patients.
Methods
A ...retrospective cohort study of hospitalized adult patients admitted to an integrated health care network in the New York metropolitan region between March 1, 2020 and April 27, 2020. The final analysis included 9,407 patients with an overall VTE rate of 2.9% (2.4% in the medical ward and 4.9% in the intensive care unit ICU) and a VTE or mortality rate of 26.1%. Most patients received prophylactic-dose thromboprophylaxis. Multivariable analysis showed significantly reduced VTE or mortality with Black race, history of hypertension, angiotensin converting enzyme/angiotensin receptor blocker use, and initial prophylactic anticoagulation. It also showed significantly increased VTE or mortality with age 60 years or greater, Charlson Comorbidity Index (CCI) of 3 or greater, patients on Medicare, history of heart failure, history of cerebrovascular disease, body mass index greater than 35, steroid use, antirheumatologic medication use, hydroxychloroquine use, maximum D-dimer four times or greater than the upper limit of normal (ULN), ICU level of care, increasing creatinine, and decreasing platelet counts.
Conclusion
In our large cohort of hospitalized COVID-19 patients, the overall in-hospital VTE rate was 2.9% (4.9% in the ICU) and a VTE or mortality rate of 26.1%. Key predictors of VTE or mortality included advanced age, increasing CCI, history of cardiovascular disease, ICU level of care, and elevated maximum D-dimer with a cutoff at least four times the ULN. Use of prophylactic-dose anticoagulation but not treatment-dose anticoagulation was associated with reduced VTE or mortality.
Abstract
Venous thromboembolism (VTE) and arterial thromboembolism (ATE) are linked by the common mechanism of thrombin generation. Historically these entities have been treated as separate ...pathophysiologic processes requiring different treatments: VTE, as the formation of fibrin-/coagulation-factor-derived thrombus in low-flow vasculature, requiring anticoagulants; versus ATE, as largely platelet-derived thrombus in high-flow vasculature, requiring antiplatelet agents. Observational studies have elucidated shared risk factors and comorbidities predisposing individuals with VTE to ATE, and vice versa, and have bolstered the strategy of dual-pathway inhibition (DPI)—the combination of low-dose anticoagulants with antiplatelet agents—to reduce thrombotic outcomes on both sides of the vasculature. Randomized clinical trials have evaluated the efficacy and safety of such regimens—mostly rivaroxaban and aspirin—in high-risk groups of patients, including those with recent acute or chronic coronary syndrome, as well as those with peripheral artery disease with or without revascularization. Studies of extended VTE prophylaxis in acutely ill medical patients have also contributed to the evidence evaluating DPI. The totality of available data supports the concept that DPI can reduce major and fatal thromboembolic outcomes, including stroke, myocardial infarction, VTE, and cardiovascular death in key patient cohorts, with acceptable risk of bleeding. Further data are needed to refine which patients derive the best net clinical benefit from such an approach. At the same time, other novel agents such as contact pathway inhibitors that reduce thrombin generation without affecting hemostasis—and thus maximize safety—should be assessed in appropriate populations.
Despite the emergence of high quality randomized trial data with the use of antithrombotic agents to reduce the risk of thromboembolism, end‐organ failure, and possibly mortality in patients with ...coronavirus disease 2019 (COVID‐19), questions still remain as to optimal patient selection for these strategies, the use of antithrombotics in outpatient settings and in‐hospital settings (including critical care units), thromboprophylaxis in special patient populations, and the management of acute thrombosis in hospitalized COVID‐19 patients. In October 2021, the International Society on Thrombosis and Haemostasis (ISTH) formed a multidisciplinary and international panel of content experts, two patient representatives, and a methodologist to develop recommendations on treatment with anticoagulants and antiplatelet agents for COVID‐19 patients. The ISTH Guideline panel discussed additional topics to be well suited to a non‐Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for Good Practice Statements (GPS) to support good clinical care in the antithrombotic management of COVID‐19 patients in various clinical settings. The GPS panel agreed on 17 GPS: 3 in the outpatient (pre‐hospital) setting, 12 in the hospital setting both in non‐critical care (ward) as well as intensive care unit settings, and 2 in the immediate post‐hospital discharge setting based on limited evidence or expert opinion that supports net clinical benefit in enacting the statements provided. The antithrombotic therapies discussed in these GPS should be available in low‐ and middle‐income countries.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
COVID-19 (coronavirus disease 2019) is associated with heightened risks of venous and arterial thrombosis and hospitalization due to respiratory failure. To assess whether prophylactic ...anticoagulation can safely reduce the frequency of venous and arterial thrombosis, hospitalization, and death in nonhospitalized patients with symptomatic COVID-19 and at least one thrombosis risk factor, we conducted the PREVENT-HD double-blind, placebo-controlled randomized trial (A Study of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic COVID-19 Infection).
PREVENT-HD was conducted between August 2020 and April 2022 at 14 US integrated health care delivery networks. A virtual trial design used remote informed consent and clinical monitoring and facilitated data collection through electronic health record integration with a cloud-based research platform. Nonhospitalized patients with symptomatic COVID-19 and at least one thrombosis risk factor were enrolled and randomly assigned to either 10 mg of oral rivaroxaban or placebo daily for 35 days. The primary efficacy outcome was time to first occurrence of a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic arterial embolism, hospitalization, or death through day 35. The principal safety end point was International Society on Thrombosis and Hemostasis critical-site or fatal bleeding. The last study visit was on day 49.
The study was terminated prematurely because of enrollment challenges and a lower-than-expected blinded pooled event rate. A total of 1284 patients underwent randomization with complete accrual of primary events through May 2022. No patients were lost to follow-up. The primary efficacy outcome occurred in 22 of 641 in the rivaroxaban group and 19 of 643 in the placebo group (3.4% versus 3.0%; hazard ratio, 1.16 95% CI, 0.63-2.15;
=0.63). No patient in either group experienced critical-site or fatal bleeding. One patient receiving rivaroxaban had a major bleed.
The study was terminated prematurely after enrollment of 32% of planned accrual because of recruitment challenges and lower-than-expected event rate. Rivaroxaban prescribed for 35 days in nonhospitalized patients with symptomatic COVID-19 at risk for thrombosis did not appear to reduce a composite end point of venous and arterial thrombotic events, hospitalization, and death.
URL: https://www.
gov; Unique identifier: NCT04508023.
Thromboprophylaxis of hospitalized patients at risk of venous thromboembolism (VTE) presents challenges owing to patient heterogeneity and lack of adoption of evidence-based methods. Intuitive ...practices for thromboprophylaxis have resulted in many patients being inappropriately prophylaxed. We conducted a narrative review summarizing system-wide thromboprophylaxis interventions in hospitalized patients. Multiple interventions for thromboprophylaxis have been tested, including multifaceted approaches such as national VTE prevention programs with audits, pre-printed order entry, passive alerts (either human or electronic), and more recently, the use of active clinical decision support (CDS) tools incorporated into electronic health records (EHRs). Multifaceted health-system and order entry interventions have shown mixed results in their ability to increase appropriate thromboprophylaxis and reduce VTE unless mandated through a national VTE prevention program, though the latter approach is potentially costly and effort- and time-dependent. Studies utilizing passive human or electronic alerts have also shown mixed results in increasing appropriate thromboprophylaxis and reducing VTE. Recently, a universal cloud-based and EHR-agnostic CDS VTE tool incorporating a validated VTE risk score revealed high adoption and effectiveness in increasing appropriate thromboprophylaxis and reducing major thromboembolism. Active CDS tools hold promise in improving appropriate thromboprophylaxis, especially with further refinement and widespread implementation within various EHRs and clinical workflows.
BACKGROUNDThe problem of noninvasive diagnosis of transplant dysfunction in patients is one of the most complex problems in transplantology at the present time. Because transplanted organs can be ...ischemic, the measurement of redox potential (RP) in blood serum reflects the prooxidant-antioxidant balance in the organism. It was hypothesized that certain dysfunctions and postoperative complications in transplant patients may be accompanied by a change in the RP of blood plasma.
METHODSMonitoring of the RP in the blood serum of patients was performed as a noninvasive method of diagnosis of transplant dysfunctions. The RP values were measured in blood serum of 63 apparently healthy subjects. Monitoring of blood serum RP was performed in 64 liver transplant patients, 59 kidney allotransplantation patients and six lung transplant patients. A total of 1,759 measurements were performed in 192 total subjects. Statistical analysis of RP values was performed using the Statistica 6.0 software package.
RESULTS AND CONCLUSIONThe proposed method is based on the electrochemical measurement of the open-circuit potential of the platinum electrode immersed in blood serum because the measured value reflects the state of equilibrium between prooxidant and antioxidant systems of the organism. Shifts in values of the RPs (open circuit potentials) observed in the course of monitoring are significantly different in patients with transplant dysfunction compared to patients with unremarkable recoveries. The analysis of monitoring allows for the development of certain diagnostic and prognostic criteria of transplant dysfunction. It is important that the proposed method is noninvasive, simple, and inexpensive.
Antithrombotic guidance statements for hospitalized patients with coronavirus disease 2019 (COVID‐19) suggest a universal thromboprophylactic strategy with potential to escalate doses in high‐risk ...patients. To date, no clear approach exists to discriminate patients at high risk for venous thromboembolism (VTE).
The objective of this study is to externally validate the IMPROVE‐DD risk assessment model (RAM) for VTE in a large cohort of hospitalized patients with COVID‐19 within a multihospital health system.
This retrospective cohort study evaluated the IMPROVE‐DD RAM on adult inpatients with COVID‐19 hospitalized between March 1, 2020, and April 27, 2020. Diagnosis of VTE was defined by new acute deep venous thrombosis or pulmonary embolism by Radiology Department imaging or point‐of‐care ultrasound. The receiver operating characteristic (ROC) curve was plotted and area under the curve (AUC) calculated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using standard methods.
A total of 9407 patients were included, with a VTE prevalence of 2.9%. The VTE rate was 0.4% for IMPROVE‐DD score 0‐1 (low risk), 1.3% for score 2‐3 (moderate risk), and 5.3% for score ≥ 4 (high risk). Approximately 45% of the total population scored high VTE risk, while 21% scored low VTE risk. IMPROVE‐DD discrimination of low versus medium/high risk showed sensitivity of 0.971, specificity of 0.218, PPV of 0.036, and NPV of 0.996. ROC AUC was 0.702.
The IMPROVE‐DD VTE RAM demonstrated very good discrimination to identify hospitalized patients with COVID‐19 as low, moderate, and high VTE risk in this large external validation study with potential to individualize thromboprophylactic strategies.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
As HIV-1 continues to spread in China from traditional high risk populations to the general public, its genetic makeup has become increasingly complex. However, the impact of these genetic changes on ...the biological and neutralization sensitivity of the virus is unknown. The current study aims to characterize the genetic, biological, and neutralization sensitivity of HIV-1 identified in China between 2004 and 2007. Based on a total of 107 full-length envelope genes obtained directly from the infected patients, we found that those viruses fell into three major genetic groups: CRF01_AE, subtype B′, and subtype C/CRF07_BC/CRF08_BC/B′C. Pseudotyped viruses built upon the viable env genes have demonstrated their substantial variability in mediating viral entry and in sensitivity to neutralization by subtype-specific plasma pools and broadly neutralizing monoclonal antibodies (bnmAb). Many viruses are resistant to one or more bnmAb, including those known to have high potency against diverse viruses from outside China. Sequence and structural analysis has revealed several mechanisms by which these resistant viruses escape recognition from bnmAb. We believe that these results will help us to better understand the impact of genetic diversity on the neutralizing sensitivity of the viruses and to facilitate the design of immunogens capable of eliciting antibodies with potency and breadth similar to those of bnmAb.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Andexanet is U.S. Food and Drug Administration (FDA) approved for the reversal of critical bleeding from factor Xa inhibitors and off-label for surgical reversal. Data are lacking on andexanet ...administration processes.
We retrospectively studied patients at a 23-hospital system who received andexanet from November 2019 to March 2023. Abstractors coded demographics, comorbidities, anticoagulant use, andexanet indication, and process times. The primary outcome was presentation-to-andexanet time; diagnosis, ordering, and administration times were calculated. Secondary outcomes included in-hospital postandexanet major thromboembolism/bleeding and mortality.
In total, 141 patients were analyzed. Andexanet indications were predominantly neurologic bleeding (85.8%). Twenty-four patients (17.0%) were transferred from nontertiary/academic centers to tertiary/academic centers. The median presentation-to-administration time was 192.5 minutes (interquartile range IQR: 108.0-337.0 minutes). Components were as follows: 72.5 minutes (IQR: 39.0-137.5 minutes) for bleeding diagnosis; 35.5 minutes (IQR: 0-96.5 minutes) for andexanet ordering; and 53.0 minutes (IQR: 38.5-78.5 minutes) for administration, which was longer at tertiary/academic hospitals (ratio 1.5, 95% confidence interval CI: 1.2-2.0,
= 0.002). Gastrointestinal or other critical bleeding (ratio 2.59, 95% CI: 1.67-4.02,
< 0.001), and tertiary/academic center treatment (ratio 1.58, 95% CI: 1.15-2.18,
= 0.005), were associated with increased time. Major thromboembolism, bleeding, and mortality occurred in 10.6, 12.0, and 22.9% of patients, respectively.
In our cohort, the median presentation-to-administration time was over 3 hours. Cumulative times were longer at tertiary/academic hospitals and for gastrointestinal/other bleeding. Postandexanet major thromboembolism/bleeding occurred more at tertiary/academic hospitals, possibly related to transfers. Prospective studies may elucidate clinical decision-making bottlenecks.
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