The clinical data obtained during the pandemic of coronavirus disease 2019 (COVID-19) indicated that this is a disease associated with an increased risk of thrombosis. Thromboembolic events in patients with COVID-19 lead to a worse clinical evolution and a poor prognosis. Some studies analyzed the prevalence and risk factors for thrombotic complications in patients with COVID-19. An observational study on 3,334 patients admitted for COVID-19 has found that 16% of patients had a thrombotic complication during hospitalization(1). 11.1% of these cases had an arterial thrombosis, 8.9% had myocardial infarction, 1.6% ischemic stroke and 1% systemic arterial thrombosis(1). Venous thromboembolism was encountered in 6.2% of patients(1). Older age, man sex, personal history of ischemic heart disease, and increased D-dimers were all risk factors for thrombosis in this study1. Almost one third of patients admitted in the intensive care unit presented thrombotic events and these were associated with a higher risk for in-hospital mortality(1).
Interestingly, another study on non-hospitalized patients with COVID-19 did not find a significant difference regarding the incidence of venous thromboembolism between these patients and those without COVID-19(2). The authors analyzed data of 220,588 patients tested for COVID-19 and reported the incidence of thrombosis in out-patients and in-patients, at 30 days. From these patients, 11.8% tested positive for infection with SARS-CoV-2; within 30 days after the positive test, 0.8% of patients developped venous thromboembolism, compared to 0.5% of patients with negative tests(2). However, this study had some limitations regarding the diagnosis of venous thromboembolism and the empirical use of anticoagulants and/or anti-inflammatory drugs. The authors of this study suggested that anticoagulants need to be studied in prospective clinical trials, to evaluate the impact of anticoagulant treatment on outpatients’ outcomes.
Regarding the pathophysiology of thrombosis in COVID-19, new data highlight that patients with severe forms of disease have sustained platelet activation, that contribute to the increased risk of thrombosis. Endhotelial injury is another pathophysiological factor that may intervene, by altering hemostasis. Cytokine storm, that appears in patients with severe forms of the disease, will also increase the risk of coagulopathy and thrombosis. The overproduction of inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin-6, interleukin-8 and interleukin-1 is considered the cause of cytokine storm, that may cause multiorgan failure and possibly death(3). Laboratory tests usually reveal increased D-dimers, thrombocytopenia, elevated fibrin degradation products, and fibrinogen(4). D-dimer levels are especially increased in patients with critical forms of disease, admitted in intensive care units(4) and may be a surrogate marker for the disease severity(5). Because of the clinical consequences of hypercoagulability in patients with COVID-19, hemogram with platelet count, peripheral blood smear, prothrombin time, aPTT, fibrinogen and D-dimers should be monitored in all hospitalized patients with COVID-19. Furthermore, these patients must be investigated and screened for deep venous thrombosis, preferably by duplex scan. Pulmonary thromboembolism, in some studies, has been more frequent than deep venous thrombosis in patients with COVID-19. A study of 1,765 patients diagnosed with COVID-19 reported an incidence of pulmonary embolism of 22%, and even higher in patients admitted in intensive care units(6). Patients with COVID-19 may also present coagulation abnormalities similar to thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, or hemolytic uremic syndrome.
Thrombotic complications in COVID-19 have some unique characteristics that must be deeper investigated, for a better management of this disease.