Thromboembolic prevention and anticoagulant therapy during the COVID-19 pandemic: updated clinical guidance from the anticoagulation forum

Barnes, Geoffrey D.; Burnett, Allison; Allen, Arthur L.; Ansell, Jack; Blumenstein, Marilyn; Clark, Nathan P.; Crowther, Mark; Dager, William E.; Deitelzweig, Steven; Ellsworth, Stacy; García, David; Kaatz, Scott; Raffini, Leslie; Rajasekhar, Anita; Beek, Andrea Van; Minichiello, Tracy

doi:10.1007/s11239-022-02643-3

Cited by 50 publications

(60 citation statements)

References 46 publications

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“…Our analysis including recently published RCTs [ 25 , 53 , 54 , 56 ] confirmed the main finding of previous meta-analyses [ 73 , 74 , 75 , 76 , 77 , 78 , 79 ] and endorsed the current guidelines ( Table S3 in Supplementary Material ) [ 80 , 81 , 82 , 83 ]. On the basis of our results, we cannot advocate for the routine use of therapeutic dose thromboprophylaxis in all COVID-19 patients either.…”

Section: Conclusion and Implications For Practice And Researchsupporting

confidence: 86%

Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis

et al. 2022

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Implementation of higher dose (HD) thromboprophylaxis has been considered in patients infected with coronavirus disease 2019 (COVID-19). Our aim was to compare HD to standard dose (SD) thromboprophylaxis in COVID-19 patients. The protocol is registered on PROSPERO (CRD42021284808). We searched for randomised controlled studies (CENTRAL, Embase, Medline and medRxviv) that compared HD to SD anticoagulation in COVID-19 and analysed outcomes such as mortality, thrombotic events, bleedings, and disease progression. The statistical analyses were made using the random effects model. Fourteen articles were included (6253 patients). HD compared with SD showed no difference in mortality (OR 0.83 [95% CI 0.54–1.28]). The use of HD was associated with a decreased risk of thrombosis (OR 0.58 [95% CI 0.44–0.76]), although with an increased risk of major bleeding (OR 1.64 [95% CI 1.25–2.16]). The cohort with D-dimer < 1 mg/mL showed no effect (OR 1.19 [95% CI 0.67–2.11]), but in the case of D-dimer > 1 mg/mL, a tendency of lower risk in the HD group was observed (OR 0.56 [95% CI 0.31–1.00]). The need for intubation in moderately ill patients showed a nonsignificant lower likelihood in the HD group (OR 0.82 [95% CI 0.63–1.08]). We cannot advocate for HD in all COVID-19 patients, although it shows some nonsignificant benefits on disease progression in those with elevated D-dimer who do not need ICU admission.

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Section: Conclusion and Implications For Practice And Researchsupporting

confidence: 86%

Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis

et al. 2022

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“…Three of the meta-analysis concluded that full-dose anticoagulation was associated with an increased risk of bleeding [ 22 – 24 ]. Expert consensus and guidance suggest therapeutic intensity anticoagulation for moderately ill hospitalized patients at risk of disease progression defined by supplemental oxygen requirement and an elevated D-dimer (> 2–4 times the upper limit of normal range) who are not at risk for anticoagulant-related bleeding [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials

Ena

Valls

2022

Clin Exp Med

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Background We carried out a meta-analysis since there is not enough evidence to recommend for or against therapeutic-dose anticoagulation compared with thromboprophylaxis in noncritically ill patients hospitalized with Covid-19. Methods We performed a systematic literature search using PubMed, Embase, Cochrane Library, and MedRxiv for randomized trials that included therapeutic-dose with low-molecular-weight heparin (LMW) or thromboprophylaxis with LMW heparin in noncritically ill patients admitted to the hospital with Covid-19. We identified five open-label studies for analysis with a total of 3220 patients. Two independent researchers selected, assessed, and extracted the data in duplicate. The outcomes evaluated were all-cause mortality, progression to invasive mechanical ventilation, incidence of venous thromboembolism, and major bleeding. The studies did not show risk for selection, detection, attrition, or reporting bias. Results Therapeutic-dose anticoagulation with LMW heparin compared with thromboprophylaxis with LMW heparin had no significant effect of all-cause death (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.67–1.07; P = 0.16; I 2 = 48%), or progression to invasive mechanical ventilation (RR 0.89; CI 0.73–1.08; P = 0.24; I 2 : 0%). Therapeutic-dose anticoagulation significantly reduced the risk of venous thromboembolic disease (RR 0.42; 95% CI 0.28–0.62; P = 0.0001; I 2 = 0%) [Number needed to treat = 37]. Major bleeding occurred in 1.79% of the patients receiving therapeutic-dose anticoagulation and in 0.97% of those receiving thromboprophylaxis [Number needed to harm 125]. Conclusion Therapeutic-dose anticoagulation in noncritically ill patients with Covid-19 could be indicated for patients at high risk of venous thromboembolic disease and low risk of bleeding.

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“…D-dimer levels have been found to be generally higher in critically ill patients than in mild patients (2.4 vs. 0.5 mg/L) ( 122 ). Standard doses of thromboprophylaxis are recommended for adults who are critically ill during hospitalization ( 123 ). Although guidelines for clinical inpatients recommend only standard or therapeutic doses, intermediate doses (defined as low molecular weight heparin bid or increased weight-based dosing that is less than the recommended therapeutic dose) are often used in clinical trials ( 123 , 124 ).…”

Section: Therapymentioning

confidence: 99%

“…Standard doses of thromboprophylaxis are recommended for adults who are critically ill during hospitalization ( 123 ). Although guidelines for clinical inpatients recommend only standard or therapeutic doses, intermediate doses (defined as low molecular weight heparin bid or increased weight-based dosing that is less than the recommended therapeutic dose) are often used in clinical trials ( 123 , 124 ). Drug distribution and metabolic clearance in patients with obesity may necessitate adjustments to dosing.…”

Section: Therapymentioning

confidence: 99%

The intersection of obesity and (long) COVID-19: Hypoxia, thrombotic inflammation, and vascular endothelial injury

Xiang

Jing

et al. 2023

Front. Cardiovasc. Med.

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The role of hypoxia, vascular endothelial injury, and thrombotic inflammation in worsening COVID-19 symptoms has been generally recognized. Damaged vascular endothelium plays a crucial role in forming in situ thrombosis, pulmonary dysfunction, and hypoxemia. Thrombotic inflammation can further aggravate local vascular endothelial injury and affect ventilation and blood flow ratio. According to the results of many studies, obesity is an independent risk factor for a variety of severe respiratory diseases and contributes to high mechanical ventilation rate, high mortality, and slow recovery in COVID-19 patients. This review will explore the mechanisms by which obesity may aggravate the acute phase of COVID-19 and delay long COVID recovery by affecting hypoxia, vascular endothelial injury, and thrombotic inflammation. A systematic search of PubMed database was conducted for papers published since January 2020, using the medical subject headings of “COVID-19” and “long COVID” combined with the following keywords: “obesity,” “thrombosis,” “endothelial injury,” “inflammation,” “hypoxia,” “treatment,” and “anticoagulation.” In patients with obesity, the accumulation of central fat restricts the expansion of alveoli, exacerbating the pulmonary dysfunction caused by SARS-CoV-2 invasion, inflammatory damage, and lung edema. Abnormal fat secretion and immune impairment further aggravate the original tissue damage and inflammation diffusion. Obesity weakens baseline vascular endothelium function leading to an early injury and pre-thrombotic state after infection. Enhanced procoagulant activity and microthrombi promote early obstruction of the vascular. Obesity also prolongs the duration of symptoms and increases the risk of sequelae after hospital discharge. Persistent viral presence, long-term inflammation, microclots, and hypoxia may contribute to the development of persistent symptoms, suggesting that patients with obesity are uniquely susceptible to long COVID. Early interventions, including supplemental oxygen, comprehensive antithrombotic therapy, and anti-inflammatory drugs, show effectiveness in many studies in the prevention of serious hypoxia, thromboembolic events, and systemic inflammation, and are therefore recommended to reduce intensive care unit admission, mortality, and sequelae.

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Thromboembolic prevention and anticoagulant therapy during the COVID-19 pandemic: updated clinical guidance from the anticoagulation forum

Cited by 50 publications

References 46 publications

Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis

Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis

Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials

The intersection of obesity and (long) COVID-19: Hypoxia, thrombotic inflammation, and vascular endothelial injury

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