Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic
disease due to a state of profound inflammation, platelet activation, and endothelial
dysfunction leading to respiratory distress and increased mortality. The incidence of
macrovascular thrombotic events varies from 10 to 30% in COVID-19 hospitalized patients
depending on the type of arterial or vein thrombosis captured and severity of illness .
Observational results in patients receiving routine low-dose prophylactic anticoagulation
(LD-PA), several institutions have recently released guidance statement to prevent
macrovascular thrombotic events with dose escalation anticoagulation. In these
recommendations, high-dose prophylactic anticoagulation (HD-PA) and therapeutic
anticoagulation (TA) can be employed either empirically or based on the body mass index and
increased D-dimer values. No randomized trial has validated this approach, and other recent
recommendations challenge this approach. Microvascular thrombotic events are also of major
concern in critically ill patients with COVID-19, even in the absence of obvious
macrovascular thrombotic events. A large review of autopsy findings in COVID-19-related
deaths reported micro thrombi in small pulmonary vessels. More generally, COVID-19-induced
endothelitis and coagulopathy across vascular beds of different organs lead to widespread
microvascular thrombosis with microangiopathy and occlusion of capillaries. Thus, in severe
COVID-19 patients requiring oxygen therapy without initial macrovascular thrombotic event, a
HD-PA or a TA could be beneficial by limiting the extension of microvascular thrombosis and
the evolution of the lung and multi-organ microcirculatory dysfunction. In a large
observational cohort of 2,773 COVID-19 patients, a lower in-hospital mortality in ventilated
patients receiving TA as compared to those receiving PA (29.1% vs. 62.7%). Our hypothesis is
dual: i) first, that TA and HD-PA strategies mitigate microthrombosis and each limit the
progression of COVID-19, including respiratory failure and multi-organ dysfunction, with in
fine a decreased mortality and duration of disease, as compared to a low-dose PA; ii) second,
that TA outperforms HD-PA in this setting.