Efficacy and Safety of D-dimer, Weight, and Renal Function-Adjusted Thromboprophylaxis in Patients with Coronavirus Disease 2019 (COVID-19).

Abstract

The activation of inflammatory and coagulation pathways, leading to hypercoagulability with reduced fibrinolysis, has emerged as pivotal mechanism in development of acute respiratory failure and thrombosis in patients with severe coronavirus disease 2019 (COVID-19).[1] Although thrombosis is a major complication in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the optimal thromboprophylaxis regimen in these patients is unknown. High rates of thrombosis, especially in those admitted to intensive care, are usually reported despite standard or even intensified thromboprophylaxis with low molecular weight heparin (LMWH). The uncertainty has been reflected in the diverse recommendations in local, national, and international guidelines.[2] [3] [4] Early studies reported that elevated D-dimer values were associated with magnified risk of thrombosis,[5] and this has been confirmed in subsequent studies,[6] even in those in which the thrombosis rate was found to be low.[7] D-dimer has also been a reliable predictor of a poor outcome, and although it is not established that these two observations are linked, large and small vessel thrombosis is prominent in the pulmonary circulation both ante- and postmortem.[8] The prominence of large and small vessel thrombosis in the pathophysiology of COVID-19 and its high frequency despite standard or sometimes increased intensity LMWH suggests that intensified prophylaxis may be beneficial. However, any benefit from this approach would need to be balanced against a possible increase in bleeding complications. The use of intensified versus standard dose LMWH is being investigated in several clinical trials, although only recently initiated in the United Kingdom. Pending the results of such studies, individual National Health Service (NHS) Trusts have developed local thromboprophylaxis guidelines for COVID-19.