Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis

Ciceri, Fabio; Beretta, Luigi; Scandroglio, Anna Mara; Colombo, Sergio; Landoni, Giovanni; Ruggeri, Annalisa; Peccatori, Jacopo; D’Angelo, Armando; Cobelli, Francesco De; Rovere‐Querini, Patrizia; Tresoldi, Moreno; Dagna, Lorenzo; Zangrillo, Alberto

doi:10.51893/2020.2.pov2

Cited by 300 publications

(138 citation statements)

References 13 publications

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“…It should be noticed however, that all patients had critical disease and randomization was performed after a median of 13 days from symptoms onset, with no available data regarding their previous anticoagulation regimen [ 8 , 11 ]. A plausible explanation could be that microvascular disease in small pulmonary blood vessels and capillaries may have already been established in critically ill patients, rendering intensified anticoagulation non-efficacious at this timepoint [ 43 ]. Similarly, a landmark study including data of 1098 critically ill patients from 3 different platforms (Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); The Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC) trial) failed to show clinical benefits with therapeutic versus standard dose and was prematurely terminated due to the prespecified futility criteria [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

Kyriakoulis

Trontzas

Rapti

et al. 2021

JCM

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Thromboprophylaxis in hospitalized patients with COVID-19 has been associated with a survival benefit and is strongly recommended. However, the optimal dose of thromboprophylaxis remains unclear. A systematic review and meta-analysis (PubMed/EMBASE) of studies comparing high (intermediate or therapeutic dose) versus standard (prophylactic dose) intensity of thrombo-prophylaxis with regard to outcome of hospitalized patients with COVID-19 was performed. Randomized and non-randomized studies that provided adjusted effect size estimates were included. Meta-analysis of 7 studies comparing intermediate versus prophylactic dose of thromboprophylaxis (2 randomized and 5 observational, n = 2009, weighted age 61 years, males 61%, ICU 53%) revealed a pooled adjusted relative risk (RR) for death at 0.56 (95% confidence intervals (CI) 0.34, 0.92) in favor of the intermediate dose. For the same comparison arms, the pooled RR for venous thromboembolism was 0.84 (95% CI 0.54, 1.31), and for major bleeding events was 1.63 (95% CI 0.79, 3.37). Meta-analysis of 17 studies comparing therapeutic versus prophylactic dose of thromboprophylaxis (2 randomized and 15 observational, n = 7776, weighted age 64 years, males 54%, ICU 21%) revealed a pooled adjusted RR for death at 0.73 (95% CI 0.47, 1.14) for the therapeutic dose. An opposite trend was observed in the unadjusted analysis of 15 observational studies (RR 1.24 (95% CI 0.88, 1.74)). For the same comparison arms, the pooled RR for venous thromboembolism was 1.13 (95% CI 0.52, 2.48), and for major bleeding events 3.32 (95% CI 2.51, 4.40). In conclusion, intermediate compared with standard prophylactic dose of thromboprophylaxis appears to be rather safe and is associated with additional survival benefit, although most data are derived from observational retrospective analyses. Randomized studies are needed to define the optimal thromboprophylaxis in hospitalized patients with COVID-19.

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Section: Discussionmentioning

confidence: 99%

High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

Kyriakoulis

Trontzas

Rapti

et al. 2021

JCM

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“…Various circulating and dysregulated inflammatory coagulation biomarkers, including fibrin(ogen), D-dimer, P-selectin, the von Willebrand Factor (VWF), C-reactive protein (CRP), and various cytokines directly bind to endothelial receptors and are likely to be indicative of a poor prognosis [240][241][242][243]. This poor prognosis is further worsened by a substantial deposition of microclots in the lungs [244][245][246]. The plasma of COVID-19 patients also carries a massive load of preformed amyloid clots and there are numerous reports of damage to erythrocytes [247][248][249] and platelets and the dysregulation of inflammatory biomarkers [240][241][242][243]250].…”

Section: Covid-19mentioning

confidence: 99%

Metabolic Influences Modulating Erythrocyte Deformability and Eryptosis

et al. 2021

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Many factors in the surrounding environment have been reported to influence erythrocyte deformability. It is likely that some influences represent reversible changes in erythrocyte rigidity that may be involved in physiological regulation, while others represent the early stages of eryptosis, i.e., the red cell self-programmed death. For example, erythrocyte rigidification during exercise is probably a reversible physiological mechanism, while the alterations of red blood cells (RBCs) observed in pathological conditions (inflammation, type 2 diabetes, and sickle-cell disease) are more likely to lead to eryptosis. The splenic clearance of rigid erythrocytes is the major regulator of RBC deformability. The physicochemical characteristics of the surrounding environment (thermal injury, pH, osmolality, oxidative stress, and plasma protein profile) also play a major role. However, there are many other factors that influence RBC deformability and eryptosis. In this comprehensive review, we discuss the various elements and circulating molecules that might influence RBCs and modify their deformability: purinergic signaling, gasotransmitters such as nitric oxide (NO), divalent cations (magnesium, zinc, and Fe++), lactate, ketone bodies, blood lipids, and several circulating hormones. Meal composition (caloric and carbohydrate intake) also modifies RBC deformability. Therefore, RBC deformability appears to be under the influence of many factors. This suggests that several homeostatic regulatory loops adapt the red cell rigidity to the physiological conditions in order to cope with the need for oxygen or fuel delivery to tissues. Furthermore, many conditions appear to irreversibly damage red cells, resulting in their destruction and removal from the blood. These two categories of modifications to erythrocyte deformability should thus be differentiated.

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“…Patients have endothelial dysfunction with a thrombo-inflammatory condition. Pulmonary microthrombosis and endothelial damage lead to V/Q mismatch (ventilation / perfusion), hypoxemia, and vasodilation [13].…”

Section: Resultsmentioning

confidence: 99%

Current conception about the pathogenesis and intensive care of severe COVID-19 (review)

Georgiyants

Корсунов

Дубров

et al. 2021

SR:MS

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The aim of the research. The aim of this work was to summarize the scientific literature data on the pathogenesis and intensive care of the severe course of coronavirus infection. Materials and methods. Databases such as PubMed, Google Scholar, Scopus and Web Of Science 2020-2021 were used for literary searches. Results. An intense inflammatory response against the SARS-CoV-2 virus in COVID-19 patients causes a cytokine storm and hypercoagulability with the development of acute respiratory distress syndrome (ARDS) and multiple organ failure. Approximately 17 % to 35 % of hospitalized patients with COVID-19 are treated in the intensive care unit, most often due to hypoxemic respiratory failure and the development of ARDS, and between 29 % and 91 % of patients in intensive care units require invasive ventilation. In addition to acute respiratory failure, hospitalized patients may have acute renal failure (9 %), liver dysfunction (19 %), coagulation disorders (10 %–25 %), and septic shock (6 %). More than 75 % of hospitalized patients require additional oxygen therapy. Respiratory support could vary from the need for oxygen supplementation through a nasal catheter to invasive ventilation or extracorporeal membrane oxygenation in patients with the most severe ARDS. The uncontrolled inflammation and coagulation seen in COVID-19 patients is similar to multifactorial ARDS, where a plethora of evidence has demonstrated the ability of long-term corticosteroid therapy (CST) to reduce inflammation-coagulation-fibroproliferation and accelerate recovery. With regard to the assessment of the benefits of therapeutic anticoagulation in patients with elevated D-dimer, the question has not yet been finally resolved, and research devoted to this is still ongoing. Conclusions. The approaches to respiratory, anticoagulant, anti-inflammatory therapy in critically ill patients with COVID-19 require further research to determine the optimal treatment tactics

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Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis

Cited by 300 publications

References 13 publications

High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

Metabolic Influences Modulating Erythrocyte Deformability and Eryptosis

Current conception about the pathogenesis and intensive care of severe COVID-19 (review)

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