The Potential Role of Coagulation Factor Xa in the Pathophysiology of COVID-19: A Role for Anticoagulants as Multimodal Therapeutic Agents

Abstract

SARS-CoV-2 infection (COVID-19) results in local and systemic activation of inflammation and coagulation. In this review article, we will discuss the potential role of coagulation factor Xa (FXa) in the pathophysiology of COVID-19. FXa, a serine protease, has been shown to play a role in the cleavage of SARS-CoV-1 spike protein (SP), with the inhibition of FXa resulting in the inhibition of viral infectivity. FX is known to be primarily produced in the liver, but it is also expressed by multiple cells types, including alveolar epithelium, cardiac myocytes, and macrophages. Considering that patients with preexisting conditions, including cardiopulmonary disease, are at an increased risk of severe COVID-19, we discuss the potential role of increased levels of FX in these patients, resulting in a potential increased propensity to have a higher infectious rate and viral load, increased activation of coagulation and inflammation, and development of fibrosis. With these observations in mind, we postulate as to the potential therapeutic role of FXa inhibitors as a prophylactic and therapeutic treatment for high-risk patients with COVID-19.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying miRNA as a Potential Multi Target Therapy to COVID-19: an In Silico Analysis

“…Other tissues such as cardiac, kidney, bowel, brain, endothelial cells and others also express the ACE2 receptor [ 7 ]. Other proteases expressed in various tissues may also cleave the Sars-CoV-2 spike protein [ 8 ] and one of them, as showed in previous studies with Sars-CoV, is the coagulation Factor Xa, colocalized with TMPRSS2 in the cell membrane [ 9 , 10 ]. Patients with preexisting conditions are more vulnerable of getting infected and develop a poor prognosis of COVID-19 [ 11 ].…”

“…Patients with preexisting conditions are more vulnerable of getting infected and develop a poor prognosis of COVID-19 [ 11 ]. Preexisting conditions such as pulmonary and cardiac diseases emerge as the highest risk groups for severe COVID-19 [ 12 ] and these patients may have a higher baseline expression of the receptor ACE2 and Factor X in these cell populations, what could put them at increased risk of host cell infection by Sars-CoV-2, with Factor X serving as one of the cleavage proteases for spike protein [ 9 ].…”

Prevalence of pulmonary embolism in patients with COVID-19 at the time of hospital admission

“…In most cases, the diagnosis of pulmonary embolism (PE) was incidental as patients underwent computed tomography pulmonary angiography (CTPA) for aggravation of their respiratory condition. Higher mortality is also described in patients with high D-Dimer levels suggesting that VTE complication may contribute to unfavourable prognosis [ 3 , 4 ]. Even though, prevalence of thromboembolic complications during ICU hospitalisation seems to be high, the prevalence of PE at hospital admission for COVID-19 is unknown and may be underestimated.…”

Waves of SARS-CoV-2 Infection and Blood Coagulation—A Link and Beyond

“…The effects of treatment with the direct oral factor Xa inhibitors apixaban, edoxaban, and rivaroxaban have been investigated during in-hospital and posthospital care of COVID-19 patients. 23 Switching from LMWH to dabigatran or edoxaban is investigated at creatinine clearances of > 30 mL/min and 30 to 15 mL/min, respectively. 24 The decision to switch from vitamin K antagonist to LMWH is determined by international normalized ratio and to direct oral anticoagulants by LMWH-independent rapid and accurate testing using patient urine samples.…”