As previously highlighted, severe COVID-19 is associated with overwhelming clinical complications of coagulation activation. A retrospective study of 107 patients who had received at least 1 month of anticoagulation therapy prior to SARS-COV-2 infection demonstrated that none developed clinically relevant thrombotic complications [97]. Prophylactic dose heparin is therefore recommended for all patients admitted to hospital with COVID-19 [98]. The enhanced inhibition of thrombin with higher doses of LMWH may further benefit patients by subsequently reducing the downstream signalling involved in inflammation, although the bleeding risk would need to be carefully considered. Clinical trials of low dose versus full dose LMWH are currently underway (NCT04372589, NCT04401293, NCT04367831, NCT04345848, NCT04373707, NCT04366960, NCT04359277 and NCT04397510) and will inform the future clinical management of COVID-19. However, in the context of diseases with a profound inflammatory response and potential lower levels of AT such as COVID-19 [8, 70], LMWH may not be effective. Indeed, anecdotal observations from clinicians caring for patients with COVID-19 report that patients continue to develop clinically identifiable clots, despite receiving prophylactic doses of LMWH, and that higher doses of heparin are needed according to factor Xa analysis, especially in patients with significantly elevated levels of D-dimer [98]. This suggests that it may be important to target coagulation proteinases that do not rely on the presence of circulating endogenous anticoagulants. In this context, some reports suggest that bivalirudin may improve haemofilter and extracorporeal membrane oxygenation filter survival [99, 100].