Increased Susceptibility for Thromboembolic Events versus High Bleeding Risk Associated with COVID-19

Abstract

The infection with the SARS-CoV-2 virus is associated with numerous systemic involvements. Besides the severe respiratory injuries and cardiovascular complications, it became obvious early on that this disease carries an increased risk of thromboembolic events, but a higher propensity for bleedings as well. We researched the medical literature over significant PubMed published articles debating on the prevalence, category of patients, the moment of occurrence, and evolution of venous thromboembolism (VTE), but also of venous and arterial “in situ” thrombosis (AT), and hemorrhagic events as well. Most researchers agree on an increased prevalence of thromboembolic events, ranging between 25 and 31% for VTE, depending on the analyzed population. For AT and hemorrhagic complications lower rates were reported, namely, about 2–3%, respectively, between 4.8 and 8%, occurring mostly in older patients, suffering from moderate/severe forms of COVID-19, with associated comorbidities. It is important to mention that patients suffering from hemorrhages frequently received thromboprophylaxis with anticoagulant drugs. As a consequence of thromboembolic and hemorrhagic complications which are both important negative prognostic factors, the evolution of patients infected with the SARS-CoV-2 virus is aggravated, determining an augmented morbidity and mortality of this population.

Prevalence and clinical implications of atrial fibrillation in patients hospitalized due to COVID-19: Data from a registry in Poland

“…It is also important emphasizing that there are some pathophysiological explanations indicating that patients who develop AF de novo during pneumonia have increased risk of bleeding events (depletion of coagulation factors and platelets as a result of inflammatory response during infection) ( 53 ). Based on the available data, it can be conservatively assumed that among patients with SARS-CoV2 infection, the risk of both thromboembolic and hemorrhagic complications to which AF patients are particularly vulnerable is at least comparable to that of patients with pulmonary infection caused by other pathogens (bacterial or viral) ( 51 , 53 , 54 ).…”

“…It is also important emphasizing that there are some pathophysiological explanations indicating that patients who develop AF de novo during pneumonia have increased risk of bleeding events (depletion of coagulation factors and platelets as a result of inflammatory response during infection) ( 53 ). Based on the available data, it can be conservatively assumed that among patients with SARS-CoV2 infection, the risk of both thromboembolic and hemorrhagic complications to which AF patients are particularly vulnerable is at least comparable to that of patients with pulmonary infection caused by other pathogens (bacterial or viral) ( 51 , 53 , 54 ). Considering the rationale presented above, it is worth emphasizing that the association between AF and pneumonia is not limited only to the COVID-19 pandemic, and the results we obtained may provide a point of consideration for patients with community acquired pneumonia caused by other causes than SARS-CoV2 virus infection.…”

A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology

“…First, SARS-CoV2 interacts with the angiotensin converting enzyme (ACE)-2 receptor on endothelial cells, which results in an increased release of the vasoconstrictor angiotensin-II and an endothelial dysfunction [ 158 ]. In addition, inflammatory response plays a primary role through complement activation, elevating levels of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-17A, which activate platelets, tissue factor and then the coagulation cascade [ 159 , 160 ]. Moreover, recent studies have shown alterations of both coagulation and fibrinolysis by multiple pathways, such as reduction of antithrombin and protein C and increasing of PAI-1 [ 160 , 161 ].…”

“…In addition, inflammatory response plays a primary role through complement activation, elevating levels of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-17A, which activate platelets, tissue factor and then the coagulation cascade [ 159 , 160 ]. Moreover, recent studies have shown alterations of both coagulation and fibrinolysis by multiple pathways, such as reduction of antithrombin and protein C and increasing of PAI-1 [ 160 , 161 ]. This hypercoagulation [ 162 ] and cytokine storm result in the alveolar thrombosis of SARS-CoV2 disease.…”

Mechanical Thrombectomy in Acute Ischemic Stroke COVID-19 and Non-COVID-19 Patients: A Single Comprehensive Stroke Center Study

“…Thromboembolic events are common and significantly contribute to the increased morbidity and mortality of COVID-19 patients. There are several inflammatory and prothrombotic mechanisms considered to be responsible for thrombosis in COVID-19, such as endothelial dysfunction, exaggerated inflammatory response that induces “cytokine storm”, and hypercoagulable state [ 3 , 4 ]. Since the onset of the COVID-19 pandemic, a considerable percentage of infected patients had documented thrombotic complications, including acute ischemic stroke (AIS).…”