Therapeutic anticoagulation in COVID-19 patients

Abstract

With great excitement, we read the recent article entitled ‘Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)’ by Lemos et al. [[1]Lemos A. do Espírito Santo D.A. Salvetti M.C. Gilio R.N. Agra L.B. Pazin-Filho A. Miranda C.H. Therapeutic versus prophylactic anticoagulation for severe COVID-19: a randomized phase II clinical trial (HESACOVID).Thromb. Res. 2020; 196: 359-366Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar]. We have some comments to share with you based on our clinical experience and understanding of the study. Under the methods section of this article, it is mentioned that patients in the standard thromboprophylaxis group received either unfractionated heparin (UFH) or enoxaparin according to the doctor's judgment. As we further go on to read Fig. 1, out of 10 patients who were assigned to the prophylactic anticoagulation group, five patients received UHF and the remaining five patients received low molecular weight heparin (LMWH). Hence, we wanted to confirm that the term LMWH used in Fig. 1 refers to enoxaparin only and not to any other LMWH. In the same context, it is important to explain why enoxaparin was not used for all 10 patients in the prophylactic group. Furthermore, we would like to know if there were any pre-defined criteria or guidelines to choose between enoxaparin and UFH in the prophylactic group. The authors did not mention when and where the participants were evaluated for enrollment in the study (emergency department, direct admit, transfer from floor). There was no mention of the duration of admission before assessing the patient for enrollment in the trial. Seven patients were excluded from the study after being assessed for the eligibility criteria. We want to know how long these patients were in the hospital before being excluded. Of note, two patients with circulatory shock requiring high dose vasopressors were excluded from the study, we would like to clarify if those patients were already on high dose vasopressors before assessing them for enrollment. Was the decision to include or exclude the patients made before the randomization or after the randomization. Among the 20 patients who underwent randomization, none of them were excluded for any reasons such as heart failure, kidney failure, severe circulatory shock, or any of the exclusion criteria of the study, which is unusual for the mechanically ventilated COVID-19 patients with severe respiratory failure. Thus, it will be worthwhile to mention if anyone experienced any complications consistent with the study's exclusion criteria after being assigned to either group. Although it was not statistically significant, patients in the prophylactic anticoagulation group were clinically worse than the therapeutic anticoagulation group based on higher PEEP and a higher rate of prone positioning, and a lower tidal volume. The results might be skewed in favor of the therapeutic group due to being less sick. Under the adverse events in Table 2, the authors mentioned that two patients from the prophylactic group and four patients from the therapeutic group developed “bleeding requiring medical attention”, while the table has reported zero minor bleeding. It will be helpful to elaborate on the meaning of this term “bleeding requiring medical attention” and how it is different from “minor bleeding”. Additionally, it was reported that a total of six patients (two from the prophylactic anticoagulation group and four from the therapeutic anticoagulation group) dropped hemoglobin more than 5 g/dL. We are interested to know if any of the patients required blood transfusion as it might give us an insight into the severity of the adverse event. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.