Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19

Xie, Junqing; Prats-Uribe, Albert; Feng, Qi; Wang, Yunhe; Paredes, Roger; Prieto-Alhambra, D

doi:10.1001/jamainternmed.2022.3858

Cited by 65 publications

(82 citation statements)

References 40 publications

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“…After SARS-Cov-2 infection, as with other viral infections, a series of persistent symptoms have been described for COVID-19, called post-COVID syndrome or long-term COVID [27]. Although none of the studied patients with genetic alterations had thrombophilic events at the time of sample collection and considering that those with D-dimer alterations were treated prophylactically with anticoagulant therapy, individuals with hereditary thrombophilia are at greater risk of developing a thrombolytic event after infection , more precisely within 30 days after a positive diagnosis for SARS-CoV-2, than those who do not have any polymorphisms in any of the factors or genes studied here [28]. As observed, high values of D-dimer are, by themselves, a risk factor for the development of thrombosis.…”

Section: Discussionmentioning

confidence: 80%

SARS-COV-2 infection in patients with hereditary thrombophilia: Is there a worsening in COVID-19 symptoms?

Peres¹,

Carvalho²,

Gascón³

et al. 2022

GSC Biol. Pharm. Sci.

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Patients with COVID-19 who progressed to a more advanced stage of the disease were observed to develop coagulation disorders. Mutations in genes encoding clotting factors, such as Prothrombin Factor II, Leiden Factor V and MTHFR are associated with the development of thromboembolism. The aim of this study was to determine the prevalence of genetic variants present in these genes in patients with COVID-19, and to associate their presence with disease severity and D-dimer values. 405 patients with different manifestations of COVID-19 were genotyped by qPCR; genotypes were associated with disease severity and D-dimer values. A slightly prevalence of the FVL mutated allele in the group with positive diagnosis was found; also, higher levels of D-dimer in patients who required treatment in intensive care were observed. Individuals with hereditary thrombophilia are at greater risk of developing a thrombolytic event after infection (long-term COVID). Our data show the benefits of performing genetic screening for hereditary thrombophilia in individuals infected with SARS-Cov-2 in order to establish, together with classical laboratory parameters, a risk factor for the development of thrombosis both during the infectious process and for post-COVID and thus avoid a vascular event.

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Section: Discussionmentioning

confidence: 80%

SARS-COV-2 infection in patients with hereditary thrombophilia: Is there a worsening in COVID-19 symptoms?

Peres¹,

Carvalho²,

Gascón³

et al. 2022

GSC Biol. Pharm. Sci.

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“…During the pandemic, it was demonstrated that thrombotic events tend to occur early in the clinical course of COVID-19 [ 54 ]. Moreover, in the outpatient setting, the incidence of VTE is higher among outpatients with certain characteristics (older age, male sex, obesity, inherited thrombophilia, no or partial vaccination) [ 55 ]. In this context, early initiation of thromboprophylaxis in outpatients with adverse prognostic factors for severe disease (candidates for hospitalization) and increased VTE risk could be regarded as a reasonable approach.…”

Section: Results—key Questions and Practical Recommendationsmentioning

confidence: 99%

Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19: A Consensus Statement Based on Available Clinical Trials

Kyriakoulis

Dimakakos

Kyriakoulis

et al. 2022

JCM

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Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients.

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“…21,22 Importantly, the polygenic risk for conventional VTE was remarkably retained for COVID-19-related VTE, which echo the finding in our previous study showing that the monogenic such as factor V Leiden mutation also consistently predisposed post-COVID-19 VTE complications. 6…”

Section: Discussionmentioning

confidence: 99%

“…21,22 Importantly, the polygenic risk for conventional VTE was remarkably retained for COVID-19related VTE, which echo the finding in our previous study showing that the monogenic such as factor V Leiden mutation also consistently predisposed post-COVID-19 VTE complications. 6 The role of genetics in variable COVID-19 representations is not yet well-understood. Although a large genome-wide association study (GWAS) was performed for COVID-19, it focused on SARS-COV-2-induced critical respiratory complications.…”

Section: Findings In Contextmentioning

confidence: 99%

“…However, a challenge remains to accurately identify individuals at sufficient risk to warrant intensive surveillance or targeted pharmacological prophylaxis. For instance, although prophylactic anticoagulation has been recommended for hospitalized patients with COVID-19 5 , evidence for its use is vastly conflicting for more critical ICU patients and milder ambulatory patients with COVID-19 [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

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Contribution of genetics and lifestyle to the risk of major cardiovascular and thromboembolic complications following COVID-19

Xie

Feng

Newby

et al. 2022

Preprint

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Clinical determinants for cardiovascular and thromboembolic (CVE) complications of COVID-19 are well-understood, but the roles of genetics and lifestyle remain unknown. We performed a prospective cohort study using UK Biobank, including 25,335 participants with confirmed SARS-CoV-2 infection between March 1, 2020, and September 3, 2021. Outcomes were hospital-diagnosed atrial fibrillation (AF), coronary artery disease (CAD), ischemic stroke (ISS), and venous thromboembolism (VTE) within 90 days post-infection. Heritable risk was represented by validated polygenic risk scores (PRSs). Lifestyle was defined by a composite of nine variables. We estimated adjusted hazard ratios (aHR) and confidence intervals (CI) using Cox proportional hazards models. In the COVID-19 acute phase, PRSs linearly predicted a higher risk of AF (aHR 1.52 per standard deviation increase, 95% CI 1.39 to 1.67), CAD (1.59, 1.40 to 1.81), and VTE (1.30, 1.11 to 1.53), but not ISS (0.92, 0.64 to 1.33). A healthy lifestyle was associated with a substantially lower risk of post-COVID-19 AF (0.70, 0.53 to 0.92), CAD (0.64, 0.44 to 0.91), and ISS (0.28, 0.12 to0.64), but not VTE (0.82, 0.48 to 1.39), compared with an unhealthy lifestyle. No evidence for interactions between genetics and lifestyle was found. Our results demonstrated that population genetics and lifestyle considerably influence cardiovascular complications following COVID-19, with implications for future personalised thromboprophylaxis and healthy lifestyle campaigns to offset the elevated cardiovascular disease burden imposed by the ongoing pandemic.

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Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19

Cited by 65 publications

References 40 publications

SARS-COV-2 infection in patients with hereditary thrombophilia: Is there a worsening in COVID-19 symptoms?

SARS-COV-2 infection in patients with hereditary thrombophilia: Is there a worsening in COVID-19 symptoms?

Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19: A Consensus Statement Based on Available Clinical Trials

Contribution of genetics and lifestyle to the risk of major cardiovascular and thromboembolic complications following COVID-19

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