Full Characterization of Thrombotic Events in All Hospitalized COVID-19 Patients in a Spanish Tertiary Hospital during the First 18 Months of the Pandemic

Abstract

The presence of a procoagulant state, COVID-19-related coagulopathy, and an increased rate of thrombotic events (TEs) is widely known about. However, descriptive studies are scarce. Here, we conducted a large retrospective study including 2894 hospitalized COVID-19 patients followed up during the first 18 months of the pandemic to completely characterize any TE. Major TEs showed a 3.45% incidence rate. TEs were associated with increased intubation/90-day mortality risk [OR = 1.71, 95% CI (1.12–2.61), p < 0.013]. Venous thrombotic events (VTEs) were more frequent than arterial thrombotic events (ATEs) (72% vs. 28%), associated with enhanced levels of D-dimer (cross-linked fibrin derivatives formed during thrombolysis), which were related to mortality but more useful for early detection of thrombosis. In this regard, D-dimer plasma levels above 2014 µg/mL at hospital admission identify TEs with 91% accuracy (AUC = 0.91, p < 0.001), rising to almost 95% (AUC = 0.94, p < 0.001) with a cut-off value of 2666 µg/mL in VTEs. Moreover, 41% of TEs occurred in patients receiving LMWH thromboprophylactic treatments in hospital or domiciliary therapies. SARS-CoV-2 infection along with a sedentary lifestyle derived from the confinement in 2020 could be more determinant than a procoagulant state in patients with risk factors for TEs. Furthermore, the normal results obtained from the thrombophilia study after the acute process are linked to this independent procoagulant state and to SARS-CoV-2-derived coagulopathy.

ADAMTS13 or Caplacizumab Reduces the Accumulation of Neutrophil Extracellular Traps and Thrombus in Whole Blood of COVID-19 Patients under Flow

“…The nucleosome (DNA/ histone complexes) may also directly interact with VWF strings, which further enhances platelet adhesion and aggregation and thrombus formation (►Fig. 5). Our findings support the potential therapeutic usage of recombinant ADAMTS13 or What is known about this topic?…”

“…[1][2][3] Thrombotic events are associated with poor outcomes such as an increased intubation and mortality rate. 4,5 More importantly, approximately 40% of thrombotic events still occurred in patients receiving low-molecular-weight heparin as a prophylaxis in hospital or home therapies. 5 In the early pandemic, more than 70% of nonsurviving coronavirus disease 2019 (COVID-19) patients fulfilled the diagnostic criteria of disseminated intravascular coagulation with increased levels of plasma D-dimer.…”

“…4 5 More importantly, approximately 40% of thrombotic events still occurred in patients receiving low-molecular-weight heparin as a prophylaxis in hospital or home therapies. 5 In the early pandemic, more than 70% of nonsurviving coronavirus disease 2019 (COVID-19) patients fulfilled the diagnostic criteria of disseminated intravascular coagulation with increased levels of plasma D-dimer. 6 However, the molecular mechanism of coagulation activation, resulting in thrombus formation in patients with severe/critical COVID-19, is not fully understood.…”

The Long Term Residual Effects of COVID-Associated Coagulopathy

“…There are many studies addressing thrombotic complications during the acute phase of COVID-19. Tamayo-Velasco et al retrospectively investigated 2894 patients in the Spanish territory, detecting a rate of major thromboembolic events reaching 3.5%, with a higher associated morbidity and mortality [ 25 ]. In an interesting propensity-matched study, De Vita and associates compared thromboembolic events in COVID-19 versus other kinds of infectious respiratory diseases [ 26 ].…”

Implication of Neutrophils Extracellular Traps in the Pathogenesis of SARS-CoV-2 pneumonia

“…In any case, it is interesting that PMNs forming NETs and VCAM1 values 14 days after hospital discharge remained higher than those of healthy controls. The increase in VCAM1 provides an explanatory basis for the thrombotic phenomena detected in these patients, mainly, although not exclusively, during the acute period of the disease [ 42 ]. Also, persistent neutrophilic and endothelial activation could be the basis of the alterations that characterize the long-COVID developed by some of the patients [ 43 ].…”