Critically Ill COVID-19 Patients May Exhibit Plasma Hypercoagulability Despite Escalated Anticoagulation

Introduction: Critically ill COVID-19 patients receiving prophylactic-dose antico-agulation exhibit high rates of thrombosis and mortality. Escalation of anticoagu-lation also does not reduce mortality and has an uncertain impact on the throm-bosis rates. The reasons why escalated doses fail to outperform prophylactic doses in reducing risks of thrombosis and death in critically ill COVID-19 patients remain unclear. We hypothesized that escalated anticoagulation would not ef-fectively prevent plasma hypercoagulability and, consequently, would not reduce the risk of thrombosis and death in some patients. Methods: We conducted a prospective multicenter study that enrolled 3860 COVID-19 patients, including 1654 critically ill. They received different doses of low-molecular-weight or unfractionated heparin, and their plasma coagulability was monitored with activated partial thromboplastin time, D-dimer, and Throm-bodynamics. A primary outcome was plasma hypercoagulability detected by Thrombodynamics. Blood samples were collected at the trough level of antico-agulation. Results: We found that escalated anticoagulation did not prevent hypercoagula-bility in 28.3% of critically ill patients at the trough level of the pharmacological activity. Critically ill patients with hypercoagulability not suppressed by anticoag-ulants had higher levels of inflammation markers and better creatinine clearance compared to critically ill patients without such hypercoagulability. Hypercoagu-lability detected by Thrombodynamics was associated with a 1.75-fold higher hazard rate for death and a 3.19-fold higher hazard rate for thrombosis. Elevated D-dimer levels were also associated with higher hazard rates for thrombosis and death, while shortened APTT were not. Simultaneous use of Thrombodynamics and D-dimer data enhanced the accuracy for predicting thrombotic events and fatal outcomes in critically ill patients. Conclusions: Thrombodynamics reliably detected hypercoagulability in COVID-19 patients and can be used in conjunction with D-dimer to assess the risk of thrombosis and death in critically ill patients. Pharmacological effect of LMWH at the trough level might be too low to prevent thrombosis in some critically ill pa-tients with severe inflammation and better creatinine clearance even if escalated doses are used.