Résumé
COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalised patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed by white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells and platelets. Immune cells, cytokines, chemokines and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate pro-inflammatory and pro-coagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2 associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism, chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalised patients with severe disease, that would target the crossroads of inflammatory and coagulation pathways.
Sujets)
Thrombose , Thromboembolisme veineux , Embolie pulmonaire , Remodelage vasculaire , Maladies transmissibles , Infections à coronavirus , COVID-19Résumé
BACKGROUND: The novel coronavirus disease (COVID-19) has led to significant mortality and morbidity, including a high incidence of related thrombotic events. There has been concern regarding hormonal contraception use during the COVID-19 pandemic, as this is an independent risk factor for thrombosis, particularly with estrogen-containing formulations. However, higher estrogen levels may be protective against severe COVID-19 disease. Evidence for risks of hormonal contraception use during the COVID-19 pandemic is sparse. We therefore conducted a living systematic review that will be updated as new data emerge on the risk of thromboembolism with hormonal contraception use in patients with COVID-19. OBJECTIVES: To determine if use of hormonal contraception increases risk of venous and arterial thromboembolism in women with COVID-19. To determine if use of hormonal contraception increases other markers of COVID-19 severity including hospitalization in the intensive care unit, acute respiratory distress syndrome, intubation, and mortality. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS: â â â â â â We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Global Health, and Scopus from inception to search update in March 2022. For the living systematic review, we monitored the literature monthly. SELECTION CRITERIA: We included all published and ongoing studies of patients with COVID-19 comparing outcomes of those on hormonal contraception versus those not on hormonal contraception. This included case series and non-randomized studies of interventions (NRSI). DATA COLLECTION AND ANALYSIS: One review author extracted study data and this was checked by a second author. Two authors individually assessed risk of bias for the comparative studies using the ROBINS-I tool and a third author helped reconcile differences. For the living systematic review, we will publish updates to our synthesis every six months. In the event that we identify a study with a more rigorous study design than the current included evidence prior to the planned six-month update, we will expedite the synthesis publication. MAIN RESULTS: We included three comparative NRSIs with 314,704 participants total and two case series describing 13 patients. The three NRSIs had serious to critical risk of bias in several domains and low study quality. Only one NRSI ascertained current use of contraceptives based on patient report; the other two used diagnostic codes within medical records to assess hormonal contraception use, but did not confirm current use nor indication for use. None of the NRSIs included thromboembolism as an outcome. Studies were not similar enough in terms of their outcomes, interventions, and study populations to combine with meta-analyses. We therefore narratively synthesized all included studies. Based on results from one NRSI, there may be little to no effect of combined hormonal contraception use on odds of mortality for COVID-19 positive patients (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.41 to 2.40; 1 study, 18,892 participants; very low-certainty evidence). Two NRSIs examined hospitalization rates for hormonal contraception users versus non-users. Based on results from one NRSI, the odds of hospitalization for COVID-19 positive combined hormonal contraception users may be slightly decreased compared with non-users for patients with body mass index (BMI) under 35 kg/m2 (OR 0.79, 95% CI 0.64 to 0.97; 1 study, 295,689 participants; very low-certainty evidence). According to results of the other NRSI assessing use of any type of hormonal contraception, there may be little to no effect on hospitalization rates for COVID-19 positive individuals (OR 0.99, 95% CI 0.68 to 1.44; 1 study, 123 participants; very low-certainty evidence). We included two case series because no comparative studies directly assessed thromboembolism as an outcome. In a case series of six pediatric COVID-19 positive patients with pulmonary embolism, one (older than 15 years of age) was using combined hormonal contraception. In a second case series of seven COVID-19 positive patients with cerebral venous thrombosis, one was using oral contraceptives. One comparative study and one case series reported on intubation rates, but the evidence for both is very uncertain. In the comparative study of 123 COVID-19 positive patients (N = 44 using hormonal contraception and N = 79 not using hormonal contraception), no patients in either group required intubation. In the case series of seven individuals with cerebral venous thromboembolism, one oral contraceptive user and one non-user required intubation. AUTHORS' CONCLUSIONS: There are no comparative studies assessing risk of thromboembolism in COVID-19 patients who use hormonal contraception, which was the primary objective of this review. Very little evidence exists examining the risk of increased COVID-19 disease severity for combined hormonal contraception users compared to non-users of hormonal contraception, and the evidence that does exist is of very low certainty. The odds of hospitalization for COVID-19 positive users of combined hormonal contraceptives may be slightly decreased compared with those of hormonal contraceptive non-users, but the evidence is very uncertain as this is based on one study restricted to patients with BMI under 35 kg/m2. There may be little to no effect of combined hormonal contraception use on odds of intubation or mortality among COVID-19 positive patients, and little to no effect of using any type of hormonal contraception on odds of hospitalization and intubation for COVID-19 patients. At a minimum, we noted no large effect for risk of increased COVID-19 disease severity among hormonal contraception users. We specifically noted gaps in pertinent data collection regarding hormonal contraception use such as formulation, hormone doses, and duration or timing of contraceptive use. Differing estrogens may have different thrombogenic potential given differing potency, so it would be important to know if a formulation contained, for example, ethinyl estradiol versus estradiol valerate. Additionally, we downgraded several studies for risk of bias because information on the timing of contraceptive use relative to COVID-19 infection and method adherence were not ascertained. No studies reported indication for hormonal contraceptive use, which is important as individuals who use hormonal management for medical conditions like heavy menstrual bleeding might have different risk profiles compared to individuals using hormones for contraception. Future studies should focus on including pertinent confounders like age, obesity, history of prior venous thromboembolism, risk factors for venous thromboembolism, and recent pregnancy.
Sujets)
COVID-19 , Contraception hormonale , Thromboembolisme veineux , Femelle , Humains , Contraceptifs/effets indésirables , COVID-19/épidémiologie , Oestrogènes/effets indésirables , Contraception hormonale/effets indésirables , Pandémies , Thrombose/épidémiologie , Thromboembolisme veineux/épidémiologieRésumé
Neutrophil extracellular traps (NETs) are extracellular fibrous networks consisting of depolymerized chromatin DNA skeletons with a variety of antimicrobial proteins. They are secreted by activated neutrophils and play key roles in host defense and immune responses. Gastrointestinal (GI) malignancies are globally known for their high mortality and morbidity. Increasing research suggests that NETs contribute to the progression and metastasis of digestive tract tumors, among them gastric, colon, liver, and pancreatic cancers. This article explores the formation of NETs and reviews the role that NETs play in the gastrointestinal oncologic microenvironment, tumor proliferation and metastasis, tumor-related thrombosis, and surgical stress. At the same time, we analyze the qualitative and quantitative detection methods of NETs in recent years and found that NETs are specific markers of coronavirus disease 2019 (COVID-19). Then, we explore the possibility of NET inhibitors for the treatment of digestive tract tumor diseases to provide a new, efficient, and safe solution for the future therapy of gastrointestinal tumors.
Sujets)
COVID-19 , Pièges extracellulaires , Tumeurs gastro-intestinales , Thrombose , Humains , Pièges extracellulaires/métabolisme , COVID-19/anatomopathologie , Granulocytes neutrophiles , Tumeurs gastro-intestinales/métabolisme , Thrombose/métabolisme , Microenvironnement tumoralRésumé
Sepsis and COVID-19 patients often manifest an imbalance in inflammation and coagulation, a complex pathological mechanism also named thromboinflammation, which strongly affects patient prognosis. Extracellular vesicles (EVs) are nanoparticles released by cells into extracellular space that have a relevant role in cell-to-cell communication. Recently, EVs have been shown to act as important players in a variety of pathologies, including cancer and cardiovascular disease. The biological properties of EVs in the mechanisms of thromboinflammation during sepsis and COVID-19 are still only partially known. Herein, we summarize the current experimental evidence on the role of EVs in thromboinflammation, both in bacterial sepsis and in COVID-19. A better understanding of EV involvement in these processes could be useful in describing novel diagnostic and therapeutic applications of EVs in these diseases.
Sujets)
COVID-19 , Vésicules extracellulaires , Sepsie , Thrombose , Humains , Inflammation , Thrombo-inflammation , COVID-19/complications , Thrombose/étiologie , Vésicules extracellulaires/anatomopathologie , Sepsie/complications , Sepsie/anatomopathologieRésumé
We present a 62-year-old patient with COVID-19 pneumonia on Veno-venous (VV) Extracorporeal Membrane Oxygenation (ECMO) with unique perturbations to pre and post oxygenator pressures due to fibrin deposition in despite being on a Heparin/Bivalirudin infusion and activated Partial Thromboplastin Time (aPTT) within therapeutic range of 60-80 seconds. On Day 8 of ECMO support, it was noticed that flows steadily decreased despite unchanged RPMs. Unlike typical blood flow to circuit pressure relationships, the circuit pressures did not correlate with the observed decreased flow. The Delta Pressure (ΔP) was not elevated. The patient's vitals were stable. On inspection post change-out, clots were noted in the oxygenator outlets. Oxygenator clots are usually associated with increased ΔP. In this scenario, clots in the oxygenator blocked 1 of the 4 outlets in the oxygenator causing the flow, pressures, and ΔP to drop consecutively. Due to reduced flow, the ΔP was not elevated despite extensive clots. The fibrin clot location in the CardioHelp ECMO circuit may lead to unexpected pressure and flow alterations. Sole reliance on ΔP as a marker for oxygenator clots may be misleading. Careful monitoring and timely diagnosis of coagulation status may lead to changes in anticoagulation goals and meaningfully impact patient outcomes.
Sujets)
COVID-19 , Oxygénation extracorporelle sur oxygénateur à membrane , Thrombose , Humains , Adulte d'âge moyen , COVID-19/complications , Oxygénateurs/effets indésirables , Thrombose/étiologie , Oxygénation extracorporelle sur oxygénateur à membrane/effets indésirables , FibrineRésumé
We investigated the efficacy, safety, and versatility of the AngioVac (AngioDynamics, Latham, NY) system for the treatment of intravascular and intracardiac masses of different origins. We prospectively enrolled all consecutive patients treated with the AngioVac system between July-2016 and November-2021 at our institution. Three configurations of the device were adopted in 44 patients: a venous-venous circuit in 21 cases (47.7%), a venous-arterial ECMO-like configuration in 20 (45.5%), and a venous-arterial-arterial circuit with 2 centrifugal pumps for left-sided cardiac masses in 3 (6.8%). Successful removal of the mass was achieved in 41 patients (93.2%), while in the other cases conversion to full sternotomy was necessary. Intraoperative complications occurred in 3 cases (6.8%), including 1 death, 1 pulmonary embolization, and 1 cardiac perforation. The AngioVac system is a valid, safe, and versatile option for the treatment of intravascular masses also in patients with prohibitive surgical risk.
Sujets)
Cardiopathies , Thrombose , Thrombose veineuse , Humains , Thrombose/étiologie , Thrombectomie , Résultat thérapeutique , Cardiopathies/étiologieRésumé
BACKGROUND: The influence of obesity on the development of thrombosis and severity of coronavirus disease 2019 (COVID-19) remains unclear. METHOD: The CLOT-COVID study was a retrospective multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 between April 2021 and September 2021 among 16 centers in Japan. The present study consisted of 2690 patients aged over 18â¯years with available body mass index (BMI), who were divided into an obesity group (BMI ≥30) (Nâ¯=â¯457) and a non-obesity group (BMI <30) (Nâ¯=â¯2233). RESULTS: The obesity group showed more severe status of COVID-19 at admission compared with the non-obesity group. The incidence of thrombosis was not significantly different between the groups (obesity group: 2.6â¯% versus non-obesity group: 1.9â¯%, pâ¯=â¯0.39), while the incidence of a composite outcome of all-cause death, or requirement of mechanical ventilation or extracorporeal membrane oxygenation during hospitalization was significantly higher in the obesity group (20.1â¯% versus 15.0â¯%, pâ¯<â¯0.01). After adjusting confounders in the multivariable logistic regression model, the risk of obesity relative to non-obesity for thrombosis was not significant (adjusted OR, 1.39; 95â¯% CI, 0.68-2.84, pâ¯=â¯0.37), while the adjusted risk of obesity relative to non-obesity for the composite outcome was significant (adjusted OR, 1.85; 95â¯% CI, 1.39-2.47, pâ¯<â¯0.001). CONCLUSIONS: In the present large-scale observational study, obesity was not significantly associated with the development of thrombosis during hospitalization; however, it was associated with severity of COVID-19.
Sujets)
COVID-19 , Thrombose , Humains , Adulte , Adulte d'âge moyen , COVID-19/complications , SARS-CoV-2 , Incidence , Études de cohortes , Études rétrospectives , Indice de gravité de la maladie , Obésité/complications , Obésité/épidémiologie , Hospitalisation , Thrombose/épidémiologie , Thrombose/étiologieRésumé
BACKGROUND: Liver transplantation is a proven management method for end-stage cirrhosis and is estimated to have increased life expectancy by 15 years. The COVID-19 pandemic posed a challenge to patients who were candid for a solid-organ transplant. It has been suggested that the outcomes of liver transplants could be adversely affected by the infection, as immunosuppression makes liver transplant candidates more susceptible to adverse effects while predisposing them to higher thrombotic events. MATERIAL AND METHODS: In this retrospective study, the cases who received liver transplants from January 2018 to March 2022 were assessed regarding early postoperative mortality rate and hepatic artery thrombosis (HAT) with COVID-19 infection. This study included 614 cases, of which 48 patients were infected. RESULTS: This study shows that the early COVID-19-related early postoperative mortality rates substantially increased in the elective setting (OR: 2.697), but the results for the acute liver failure were insignificant. The average model for end-stage liver disease score increased significantly during the pandemic due to new regulations. Although mortality rates increased during the pandemic, the data for the vaccination period show that mortality rates have equalised with the prepandemic era. Meanwhile, COVID-19 infection is assumed to have increased HAT by 1.6 times in the elective setting. CONCLUSION: This study shows that COVID-19 infection in an acute liver failure poses comparatively little risk; hence transplantation should be considered in such cases. Meanwhile, the hypercoagulative state induced by the infection predisposes this group of patients to higher HAT rates.
Sujets)
COVID-19 , Maladie du foie en phase terminale , Défaillance hépatique aigüe , Transplantation hépatique , Thrombose , Humains , Transplantation hépatique/effets indésirables , COVID-19/épidémiologie , Études rétrospectives , Maladie du foie en phase terminale/épidémiologie , Maladie du foie en phase terminale/chirurgie , Pandémies , Indice de gravité de la maladie , Défaillance hépatique aigüe/étiologie , Thrombose/épidémiologie , Thrombose/étiologieRésumé
Platelets are essential for the formation of a haemostatic plug to prevent bleeding, while neutrophils are the guardians of our immune defences against invading pathogens. The interplay between platelets and innate immunity, and subsequent triggering of the activation of coagulation is part of the host system to prevent systemic spread of pathogen in the blood stream. Aberrant immunothrombosis and excessive inflammation can however, contribute to the thrombotic burden observed in many cardiovascular diseases. In this review, we highlight how platelets and neutrophils interact with each other and how their crosstalk is central to both arterial and venous thrombosis and in COVID-19. While targeting platelets and coagulation enables efficient antithrombotic treatments, they are often accompanied with a bleeding risk. We also discuss how novel approaches to reduce platelet-mediated recruitment of neutrophils could represent promising therapies to treat thrombosis without affecting haemostasis.
Sujets)
COVID-19 , Pièges extracellulaires , Thrombose , Humains , Granulocytes neutrophiles , PlaquettesRésumé
Aim To evaluate the incidence and characteristic features of left atrial appendage (LAA) thrombosis in patients with persistent nonvalvular atrial fibrillation (AF) after COVID-19.Material and methods Transesophageal echocardiography (TEE) was performed for 469 patients (57.4â% males; mean age, 64.0 [58.0; 70.0] years) with persistent nonvalvular AF before scheduled sinus rhythm restoration. In 131 of these patients (27.9â%), the most recent episode of arrhythmia developed during the coronavirus infection. The time from the onset of COVID-19 to TEE was 145 [62; 303] days. All patients received an adequate anticoagulant therapy, in most cases, with direct oral anticoagulants for at least 3 weeks preceding the study.Results A LAA thrombus was detected in 20 (5.9â%) patients who have had no coronavirus infection and in 19 (14.5â%) patients after COVID-19 (Ñ=0.0045). 18 of 19 (94.7â%) thrombi found in patients who have had COVID-19 were mural whereas only 5 (25.0â%) of such thrombi were found in patients who have had no COVID-19 (p<0.0001). In the absence of LAA thrombus, the LAA emptying velocity was 32.0 [25.0; 40.0]âcm/sec whereas in the presence of a mural thrombus, it was 25.0 [20.0; 32.3]âcm/sec, and in the presence of a typical thrombus, it was 17.0 [13.5; 20.0]âcm/sec (Ñ<0.0001). A Kaplan-Meier analysis showed that the median time of mural thrombus dissolution was 35.0 (95â% confidence interval (CI), 24.0-55.0) days and for a typical thrombus, this time was 69.0 (95â% CI, 41.0-180.0) days (Ñ=0.0018).Conclusion Patients with persistent AF who have had COVID-19 had LAA thrombosis 2,5 times more frequently and, in most cases, the thrombus was mural. Mural thrombi, in contrast to typical, are not associated with a pronounced decrease in LAA emptying velocity and dissolve twice as fast as typical thrombi with an adequate anticoagulant treatment.
Sujets)
Auricule de l'atrium , Fibrillation auriculaire , COVID-19 , Cardiopathies , Thrombose , Mâle , Humains , Adulte d'âge moyen , Femelle , Fibrillation auriculaire/complications , Auricule de l'atrium/imagerie diagnostique , COVID-19/complications , Anticoagulants , Thrombose/étiologie , Échocardiographie transoesophagienne/effets indésirables , Cardiopathies/complicationsRésumé
Fondaparinux sodium is a chemically synthesized selective factor Xa inhibitor approved for the prevention and treatment of venous thromboembolic events, that is, deep vein thrombosis, pulmonary embolism, and superficial vein thrombosis, in acutely ill (including those affected by COVID-19 or cancer patients) and those undergoing surgeries. Since its approval in 2002, the efficacy and safety of fondaparinux is well demonstrated by many clinical studies, establishing the value of fondaparinux in clinical practice. Some of the advantages with fondaparinux are its chemical nature of synthesis, minimal risk of contamination, 100% absolute bioavailability subcutaneously, instant onset of action, a long half-life, direct renal excretion, fewer adverse reactions when compared with direct oral anticoagulants, and being an ideal alternative in conditions where oral anticoagulants are not approved for use or in patients intolerant to low molecular weight heparins (LMWH). In the last decade, the real-world use of fondaparinux has been explored in other conditions such as acute coronary syndromes, bariatric surgery, in patients developing vaccine-induced immune thrombotic thrombocytopenia (VITT) and in pregnant women with heparin-induced thrombocytopenia (HIT), or those intolerant to LMWH. The emerging data from these studies have culminated in recent updates in the guidelines that recommend the use of fondaparinux under various conditions. This paper aims to review the recent data and the subsequent updates in the recommendations of various guidelines on the use of fondaparinux sodium.