Thromboprophylaxis Strategies for Hospitalized Patients With COVID-19

Abstract

We read with interest the updated guidelines for thromboprophylaxis in patients with COVID-19 in this issue of CHEST.1Moores L.K. Tritschler T. Brosnahan S. et al.Thromboprophylaxis in patients with COVID-2019: a brief update to the CHEST guideline and expert panel report.Chest. 2022; 162: 213-225Abstract Full Text Full Text PDF Scopus (11) Google Scholar As stated in this and the previous version,2Moores L.K. Tritschler T. Brosnahan S. et al.Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST guideline and expert panel report.Chest. 2020; 158: 1143-1163Abstract Full Text Full Text PDF PubMed Scopus (376) Google Scholar the intent of these guidelines is to provide guidance regarding the optimal thromboprophylaxis strategies for VTE. However, although most of the recommendations align with the available evidence, it is our opinion that the first recommendation regarding the subgroup of moderately ill (noncritical) hospitalized patients does not. Although the risk ratio for VTE was 0.48 in favor of therapeutic anticoagulation (TA), additional meta-analyses of the risk difference for the same data show that, compared with prophylactic anticoagulation, TA was associated with a reduction of only 1.3% (95% CI, 0.6%-2.5%) in the risk of VTE with an associated increase in the risk of major bleeding of 0.9% (95% CI, 0.6%-1.7%). In addition, a meta-analysis of the reported main outcome for each of the four studies shows a risk ratio of 0.8 (95% CI, 0.5-1.2), suggesting no advantage of the intervention across all trials with the caveat that the main outcomes designed for all four studies were not the same. Therefore, the recommendation favoring TA was made on the basis of the reported advantage on organ support-free days for the multiplatform trial only, which amounted to only 4% (95% CI, 0.5%-7.2%).3Lawler P.R. Goligher E.C. Berger J.S. et al.Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19.N Engl J Med. 2021; 385: 790-802Crossref PubMed Scopus (245) Google Scholar In our opinion, this deviates from the original intent of the guidelines, making their adoption confusing and potentially harmful. In addition, the generalizability of the findings for the four trials is questionable as, overall, they included only 11% of more than 32,000 screened patients. In particular, the risk of bleeding is significant in these patients as shown by a systematic review and meta-analysis, including more than 18,000 hospitalized patients with COVID-19, reporting a pooled incidence of total and major bleeding of 7.8% and 3.9%, respectively, with the highest pooled incidence estimate among patients receiving intermediate- or full-dose anticoagulation (21.4%).4Jiménez D. García-Sanchez A. Rali P. et al.Incidence of VTE and bleeding among hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis.Chest. 2021; 159: 1182-1196Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar In another cohort study of 1,965 patients receiving either intermediate or therapeutic anticoagulation, major bleeding events occurred in 5.7%.5Demelo-Rodriguez P. Farfán-Sedano A.I. Pedrajas J.M. et al.RIETE-BLEEDING Investigators. Bleeding risk in hospitalized patients with COVID-19 receiving intermediate- or therapeutic doses of thromboprophylaxis.J Thromb Haemost. 2021; 19: 1981-1989Crossref PubMed Scopus (16) Google Scholar These figures differ from those reported in the four trials included in the guidelines, suggesting again a potential issue of generalizability. We strongly believe that despite emerging data, TA strategies should not be considered standard of care yet, and if they are used outside of randomized trials, they must be executed very carefully on a case-by-case basis with multidisciplinary input and careful documentation. Financial/nonfinancial disclosures: None declared. Thromboprophylaxis in Patients With COVID-19: A Brief Update to the CHEST Guideline and Expert Panel ReportCHESTVol. 162Issue 1PreviewPatients hospitalized with COVID-19 often exhibit markers of a hypercoagulable state and have an increased incidence of VTE. In response, CHEST issued rapid clinical guidance regarding prevention of VTE. Over the past 18 months the quality of the evidence has improved. We thus sought to incorporate this evidence and update our recommendations as necessary. Full-Text PDF ResponseCHESTVol. 162Issue 1PreviewWe agree with Porres-Aguilar and colleagues that therapeutic-dose anticoagulation should not be the standard of care for all noncritically ill, hospitalized patients with COVID-19 and, therefore, we provided several specifications to our recommendation in the recent update to the CHEST guideline and expert panel report.1 We specifically suggest that heparin be used, because its benefits do not appear to extend to other anticoagulants, and that therapeutic dosing be considered only in patients who are at low risk of bleeding. Full-Text PDF