Thromboembolic events in patients with SARS-CoV-2

Many physicians treating patients with SARS-CoV-2 have noted an increased incidence of thromboembolic events such as catheter thrombosis, deep venous thrombosis, and pulmonary embolism. Anecdotal as it seems, the increasing discussion and concern about an increased thromboembolic risk in these cannot be ignored. The current evidence is circumstantial at best but portrays a picture of a hypercoagulable state in these patients. Large observational studies that have described the clinical characteristics and outcomes of patients with SARS-CoV-2 have failed to report the thromboembolic outcomes. To date, only two studies have reported the incidence of thromboembolic events in patients with SARS-CoV-2. The first study was an observational study of patients treated in an intensive care unit in China.¹ Of 81 patients, 20 (24.7%) had developed lower extremity deep venous thrombosis. The second study was an observational study from The Netherlands that examined the incidence of both venous and arterial thromboembolic events in patients with SARS-CoV-2 admitted to the intensive care unit.² Of a total of 184 patients, 28 (15.2%) had developed venous thromboembolic events (pulmonary embolism in 25, lower extremity deep venous thrombosis in 1, and upper extremity catheter-related venous thrombosis in 2) and three (2.2%) had developed arterial thromboembolic events (ischemic stroke in all 3). Although no direct comparison is possible, the incidence of venous thromboembolism in these studies seemed to be considerably greater than the incidence of venous thromboembolism of 9.9% reported by a recent randomized controlled trial of intensive care unit patients.³

Several studies have also suggested that patients with SARS-CoV-2 might have a hypercoagulable state that could predispose them to the occurrence of thromboembolic events. A case series from Singapore reported clot wave analysis parameters that were consistent with hypercoagulability in critically ill patients with SARS-CoV-2.⁴ A retrospective study from China reported that patients who received had anticoagulation therapy seemed to have a better prognosis, especially if they had a higher plasma D-dimer concentration.⁵ Finally, a case series from the United States described the successful use of intravenous tissue plasminogen activator for the treatment of acute respiratory distress syndrome in three patients who had not responded to conventional treatment.⁶ The results of that case series suggest that pulmonary microvascular thrombosis might be responsible for the high mortality rate in patients with SARS-CoV-2 and acute respiratory distress syndrome. The theory regarding pulmonary microvascular thrombosis has been further corroborated by a Chinese study, which performed postmortem examinations of patients who had died of SARS-CoV-2. They reported that thrombosis was commonly found in the small vessels, lungs, and, even, some extrapulmonary organs.⁷

Although these studies cannot prove that the hypercoagulable state is a direct causative effect of SARS-CoV-2 infection, it is apparent that patients with SARS-CoV-2 could have a predilection to the occurrence of thromboembolic events. As such, the International Society on Thrombosis and Haemostasis has recommended that all patients with SARS-CoV-2 infection, including those who are not critically ill, should receive prophylactic low-molecular-weight heparin, unless contraindicated.⁸ Some institutions are also considering systemic anticoagulation for patients with SARS-CoV-2 and high D-dimer levels. This is a serious issue that should not be overlooked. We strongly urge the medical community to report their experience with thromboembolic events in patients with SARS-CoV-2.