What We Know (and Do not Know) Regarding the Pathogenesis of Pulmonary Thrombosis in COVID-19

Abstract

The clinical course of coronavirus disease 2019 (COVID-19) is often complicated by the onset of venous thrombosis and thromboembolism (VTE), encompassing also pulmonary thrombosis. Recent statistics attests that the cumulative frequency of VTE can be as high as 30% in COVID-19 hospitalized patients, increasing to nearly 40 to 70% (depending on systematic screening) in those with severe illness, mechanical ventilation, or intensive care unit admission. The risk of venous thrombosis seems mostly limited to the active phase of disease, and is directly associated with some genetic (i.e., inherited prothrombotic predisposition) and demographical factors (male sex, overweight/obesity), disease severity (risk increasing progressively from hospitalization to development of severe illness, being the highest in patients needing mechanical ventilation and/or intensive care), presence and extent of pulmonary disease, coexistence of multiple risk factors (immobilization, mechanical ventilation, co- or superinfections), along with increased values of inflammatory and thrombotic biomarkers. At least three different phenotypes of pulmonary thrombosis may develop in COVID-19 patients, one caused by typical embolization from peripheral venous thrombosis (e.g., deep vein thrombosis), a second type triggered by local inflammation of nearby pulmonary tissue, and a third one mostly attributable to the prothrombotic state consequent to the pronounced systemic inflammatory response (i.e., the so-called cytokine storm) that is frequently observed in COVID-19. Although the pathogenesis of these three conditions has different features, their discrimination is essential for diagnostic and therapeutic purposes. The prognosis of COVID-19 patients who develop pulmonary thrombosis is also considerably worse than those who do not, thus probably needing frequent monitoring and more aggressive therapeutic management.

Autoimmune Diseases Affecting Hemostasis: A Narrative Review

“…The identification of APS requires both the presence of clinical evidence of thrombosis or pregnancy/fetal morbidity, as well as laboratory evidence of presence of aPL. For the former, thrombosis is already a feature of severe COVID-19 through multiple pro-thrombotic mechanisms [ 78 , 79 , 80 , 81 , 82 ], so this confounds the clinical evidence required to identify APS. For the latter, aPL are present in a proportion of asymptomatic patients (potentially up to 5% of the general population may be positive in one or more aPL tests).…”

Strength of Anticoagulation in Moderate to Severe COVID-19 Illness: In Medio Stat Virtus?

“…13 As far as the onset of thrombotic episodes during SARS-CoV-2 infection is concerned, either localized or systemic, several lines of evidence now attest that such risk is considerably spotted and multifaceted. 14 A recent meta-analysis of 21 studies, totaling 5,296 patients, reported a significantly increased risk of VTE in patients with elevation of some well-known laboratory biomarkers such as D-dimer, troponin, and C-reactive protein (CRP), as well as with overall length of hospitalization, intubation, and inotropic drugs requirement, while no substantial associations were found with other conventional risk factors such as personal history of thrombosis, cancer, and overweight. 15 These results could be confirmed in another study, which concluded that the risk of PE was nearly 60% higher in males, nearly fourfold higher in patients needing mechanical ventilation, and threefold higher in those admitted to the ICU.…”

Has “D-dimeritis” worsened during the COVID-19 pandemic?

“…2 An increased risk of developing acute thrombotic evens, both venous and arterial, is a hallmark of severe/critical COVID-19 cases, as comprehensively described elsewhere. [3][4][5] Thus, D-dimer values are very frequently elevated in patients with SARS-CoV-2 infection, correlate with the clinical phenotype, and predict the risk of developing thrombosis and multiple organ failure. 6,7 It is hence not surprising that the number of D-dimer test requests may have undergone a paramount increase throughout the COVID-19 pandemic, whereby the value of this biomarker may provide a valuable, almost unreplaceable contribution to the diagnostic approach, clinical decision making, risk stratification and managed care of patients with COVID-19.…”