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

Abstract

Coronavirus disease 2019 (COVID-19) predisposes to deep vein thrombosis (DVT) and pulmonary embolism (PE) particularly in mechanically ventilated adults with severe pneumonia. The extremely high prevalence of DVT in the COVID-19 patients hospitalized in the intensive care unit (ICU) has been established between 25 and 84% based on studies including systematic duplex ultrasound of the lower limbs when prophylactic anticoagulation was systematically administrated. DVT prevalence has been shown to be markedly higher than in mechanically ventilated influenza patients (6–8%). Unusually high inflammatory and prothrombotic phenotype represents a striking feature of COVID-19 patients, as reflected by markedly elevated reactive protein C, fibrinogen, interleukin 6, von Willebrand factor, and factor VIII. Moreover, in critically ill patients, venous stasis has been associated with the prothrombotic phenotype attributed to COVID-19, which increases the risk of thrombosis. Venous stasis results among others from immobilization under muscular paralysis, mechanical ventilation with high positive end-expiratory pressure, and pulmonary microvascular network injuries or occlusions. Venous return to the heart is subsequently decreased with increase in central and peripheral venous pressures, marked proximal and distal veins dilation, and drops in venous blood flow velocities, leading to a spontaneous contrast “sludge pattern” in veins considered as prothrombotic. Together with endothelial lesions and hypercoagulability status, venous stasis completes the Virchow triad and considerably increases the prevalence of DVT and PE in critically ill COVID-19 patients, therefore raising questions regarding the optimal doses for thromboprophylaxis during ICU stay.

Histone H3 Cleavage in Severe COVID-19 ICU Patients

“…The more severe cases usually develop bilateral interstitial pneumonia and moderate to severe hypoxemia, resulting in respiratory failure and acute respiratory distress syndrome (ARDS) (Zhou et al, 2020). Recent data show that the most serious syndrome is associated with early localized proinflammatory cytokine release (Wang et al, 2020), hypercoagulability (Middleton et al, 2020;Voicu et al, 2020), and neutrophil extracellular trap (NET) formation (Zuo et al, 2020;Busch et al, 2020).…”

A Case of Phlegmasia Cerulea Dolens in a Patient With COVID-19, Effectively Ttreated With Fasciotomy and Mechanical Thrombectomy

“…Several studies have shown that the use of anticoagulation is associated with lower mortality, especially in those critically ill, but there is still no consensus regarding the optimal level of anticoagulation [ 4 , 5 , 6 ]. The survival benefit of anticoagulation supports the initial speculation that the COVID-19 induced coagulopathy is secondary to a robust inflammatory response, leading to endothelial dysfunction, and a heightened coagulopathic cascade [7] . Our patient had a huge elevation in D-dimer levels on hospital day three and developed extensive iliofemoral DVT although he was receiving thromboprophylaxis with LMWH.…”

Calculated plasma osmolality at hospital admission correlates well with eGFR and D-Dimer, a simple outcome predictor and guiding tool for management of severe COVID-19 patients

“…Severe COVID-19 is characterized by elevation of d-dimer and marked inflammatory and prothrombotic state. Mechanical ventilation, immobilized state, venous stasis enhance the risk, thus requiring thromboprophylaxis [ 32 ]. Usage of systemic glucocorticoids increase the risk further [ 33 ].…”