key: cord-0981294-ybnspfyu
authors: Prandoni, Paolo; Cattelan, Anna Maria; Carrozzi, Laura; Leone, Lucia; Filippi, Lucia; De Gaudenzi, Egidio; Villalta, Sabina; Pesavento, Raffaele
title: The hazard of fondaparinux in non-critically ill patients with COVID-19: Retrospective controlled study versus enoxaparin
date: 2020-09-17
journal: Thromb Res
DOI: 10.1016/j.thromres.2020.09.024
sha: 589e1765be614245967f06a8f5c014011bc90216
doc_id: 981294
cord_uid: ybnspfyu

nan

Dear Editors-in-Chief, COVID-19 (acronym of COronaVIrus Disease 2019) is an infectious respiratory disease, responsible for a worldwide pandemic, with a high rate of venous and arterial thrombotic complications. These complications have recently been reported to occur in patients with COVID-19 disease regardless of the use of prophylactic doses of low-molecular-weight heparin (LMWH) [1, 2] . Although their incidence is higher in the most severe patients, it has been reported to be substantial also in those with less severe disease [1, 3, 4] .

Fondaparinux, an indirect inhibitor of factor Xa that is injected subcutaneously and is highly effective for protection against VTE in admitted medical patients [5] , was found to be more effective than and as safe as LMWH in high-risk surgical patients, such as candidates to major orthopedic surgery [6] . These findings are consistent with those achieved by several oral inhibitors of factor Xa not only in major but also in minor orthopedic surgery of the legs [6] [7] [8] . Unlike oral Xa inhibitors, fondaparinux does not interfere with antiviral drugs, and, therefore, it qualifies as a potential candidate to replace LMWH for prevention of thrombotic complications in high-risk patients, such as those admitted to medical departments because of a non-severe COVID-19 infectious disease. Surprisingly enough, this drug has not been investigated yet in this clinical setting. Accordingly, we decided to retrieve the medical charts of non-critically ill COVID-19 patients admitted to seven medical departments in the Northern Italy during the current pandemic, and to compare the incidence of venous and arterial thrombotic complications, as well as that of major and clinically relevant bleeding complications between patients allocated to prophylactic doses of enoxaparin and those given prophylactic doses of fondaparinux. Patients who for any reason did not receive antithrombotic prophylaxis were excluded, as were those who were prescribed with fondaparinux. Table 1 shows the main baseline demographic and clinical characteristics of the recruited patients, which were all fully comparable between the two study groups. To of antiviral, antibiotic and anti-inflammatory drugs. The number of patients who deteriorated clinically, thus requiring admission to Intensive Care Units was similar (6 among enoxaparin and 4 among fondaparinux recipients), as was the number of patients who died (8 and 7, respectively). Except for two patients who died because of acute coronary syndrome (one in each group), in all other cases the death was attributed to disease-related complications.

A similarly proportion of clinically symptomatic and objectively confirmed venous or arterial thrombotic complications was shown in the two study groups: 5 episodes Table 2 . No bleeding was fatal. All of them led to discontinuation of thromboprophylaxis.

Although selection bias is likely to have occurred, because of the lack of a randomized allocation to the treatment groups, our conclusions are plausible, because of the full comparability in the baseline and clinical characteristics of the recruited patients. In addition, an identical approach was used to identify and classify the thrombotic and hemorrhagic complications according to widely accepted definitions.

While the rate of clinically symptomatic and objectively confirmed venous or arterial thrombotic complications was similar in the two study groups, that of major or clinically relevant bleeding complications was remarkably higher among fondaparinux recipients. The hemorrhagic potential of fondaparinux in low, prophylactic doses was somewhat unexpected, as it contrasts with that seen in other medical [5] and surgical settings [6] . It was found to mirror that of (sub)therapeutic doses of LMWH in the same clinical scenario [9] . A potential explanation is the Based on our study results, the use of fondaparinux in place of LMWH in patients with non-critically ill COVID-19 infectious disease should be discouraged. Whether these conclusions apply to patients with a more severe disease remains to be demonstrated. Values in parentheses are percentages unless otherwise indicated 

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