Rebuttal to letter “Is thromboprophylaxis with high-dose enoxaparin really necessary for COVID-19 patients? A new “prudent” randomised clinical trial”

Dear Sir,

We appreciate the interest of Cattaneo and Morici in the SISET position paper on COVID-19 and haemostasis^1,2.

In their comments¹, they underline several interesting points relevant to the management of venous thrombosis prophylaxis in COVID-19 patients.

We agree that stronger evidence from properly designed, randomised controlled trials is urgently needed. It would be desirable that clinical trials compare efficacy and safety of different doses and schedules of administration of either unfractionated heparin (UFH) or low molecular weight heparin in improving the clinical course of the disease in a well-characterised clinical subset of COVID-19 patients. Achieving this goal requires careful stratification of their thrombotic risk, taking into consideration the care setting (i.e., intensive or less intensive care units) in which the patients where treated. Apparently, the trial designed by Cattaneo and Morici will only enrol patients admitted to nonintensive care units.

Pending further evidence, our recommendation regarding the need to provide antithrombotic prophylaxis to all hospitalised COVID-19 patients, is a reasonable one, and is in agreement with that provided by the World Health Organization³. Indeed, it is well known that hospitalised patients with acute medical illness, including infections such as pneumonia, are at increased risk of VTE.

We are aware that there are no risk assessment models that have been specifically validated in this particular setting. Nevertheless, most hospitalised COVID-19 patients have multiple risk factors for venous thromboembolism (VTE), such as age >70 years, reduced mobility, and obesity, besides the impending inflammatory status, meaning they should be considered for VTE prophylaxis according to the Padua score. Moreover, there are increasing laboratory data showing a state of hypercoagulability in severe COVID-19 patients, thus supporting the use of antithrombotic prophylaxis or treatment⁴.

In our paper, we wanted to suggest that the rate of micro-pulmonary embolism could be actually higher than that reported, since it is difficult to obtain a confirmed diagnosis, either objective or autoptical. Indeed, we are aware that the question about the rate of objectively confirmed VTE in more severe COVID-19 patients is still unanswered, given the paucity of data about the incidence of VTE according to the severity of the disease. In this regard, an incidence of symptomatic pulmonary embolism of approximately 20% has been reported in COVID-19 patients admitted to intensive care units, despite properly administered VTE prophylaxis⁵.

We strongly endorse any effort by the scientific community to rapidly collect evidence from basic and clinical research to improve our ability to tackle this global health issue.