Coagulation dysfunction in COVID-19: The interplay between inflammation, viral infection and the coagulation system

Abstract

COVID-19 is a new pandemic, caused by Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-Cov2) infection and characterized by a broad spectrum of clinical manifestations. Inflammation and the innate immune system have been recently recognized as pivotal players in the most severe forms, characterized by significantly elevated levels of pro-inflammatory cytokines. In this setting, several studies have also reported the presence of abnormalities in coagulation parameters and platelets count, possibly identifying a subgroup of patients with poor prognosis. Some reports of full-blown thromboembolic events are emerging. Among the possible mechanisms underlying coagulation dysfunction, the so-called "cytokine storm" seems to play a pivotal role. Other candidate factors include virus-specific mechanisms, related to the virus interaction with renin angiotensin system (RAS) and the fibrinolytic pathway, but also comorbidities affecting these patients. Coagulation dysfunction is therefore a candidate risk factor for adverse outcomes in COVID-19 and should be carefully addressed in clinical practice.

Stroke in patients with COVID-19: Clinical and neuroimaging characteristics

“…For cerebrovascular disease, some of the predictors of poor outcome were in line with the experience in non-COVID stroke cases, such as older age, higher NIHSS at admission, baseline glucose, and creatinine levels, while others appear to be more specific to this particular population (e.g. thrombocytopenia, lymphocytopenia, and elevated levels of D-dimer and LDH) [ 7 , 11 , 13 , 19 , 60 , 62 ].…”

“…Following the binding of the virus, there is an important decrease of expression and activity of ACE2 due to cleavage and shedding of its extracellular component. The downregulation of ACE2 expression reduces its protective effects and exacerbates the injurious actions (prothrombotic and proinflammatory) of angiotensin II [ 14 , 62 , 63 ]. The host responds to the aggression of SARS-CoV-2 by stimulation of immune cells (the role of macrophages seems particularly relevant) which lead to the delivery of cytokines, comprising IL-6 and IL-1β [ 15 ].…”

Pathophysiological Processes Underlying the High Prevalence of Deep Vein Thrombosis in Critically Ill COVID-19 Patients

“…The cytokine storm described in COVID-19 patients is a major pathophysiological bridge between inflammation and thrombosis. Although its complex pathophysiology is beyond the scope of this mini-review, the relationship to thrombosis of one of the main factors involved, IL-6, found in very high levels in COVID-19 patients ( Lazzaroni et al, 2020 ) must be acknowledged. Notably, IL-6 up-regulates fibrinogen levels, activates tissue factor expression, but also increases factor VIII level, through endothelial injury or activation by complex formed by IL-6 and IL6-receptor and subsequent von Willebrand factor release ( Joly et al, 2020 ).…”

Isolated Radial Vein Thrombosis: Upper Extremity Deep Vein Thrombosis in a Patient With COVID-19 Infection

“…The role of COVID-19 on the angiotensin-converting enzyme 2 receptors on endothelial cells and cytokine storm has been found to play a role in thromboembolic complications [ 5 ]. Patients with COVID-19 infection with increased D-Dimer, low platelets, and prolonged prothrombin time on initial presentation have a high risk of developing venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) [ 6 , 7 ]. Thrombotic events, including PE, DVT, myocardial infarction (MI), and a cerebrovascular accident, have been reported in patients with COVID-19 infection [ 8 , 9 ].…”