Pretransplant Genetic Susceptibility: Clinical Relevance in Transplant-Associated Thrombotic Microangiopathy

Gavriilaki, Eleni; Touloumenidou, Tasoula; Batsis, Ioannis; Mallouri, Despina; Psomopoulos, Fotis; Tsagiopoulou, Maria; Koutra, Maria; Yannaki, Evangelia; Papalexandri, Apostolia; Taylor, P; Nikolousis, Emmanuel; Stamouli, Maria; Holbro, Andreas; Baltadakis, Ioannis; Liga, Maria; Spyridonidis, Alexandros; Tsirigotis, Panagiotis; Charchalakis, Nikolaos; Tsakiris, Dimitrios Α.; Passweg, J.; Stamatopoulos, Kostas; Anagnostopoulos, Αchilles

doi:10.1055/s-0040-1702225

Cited by 39 publications

(34 citation statements)

References 62 publications

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“…Taking into account previous experience from other coronaviruses, several recent studies have implicated complement activation as part of the vicious cycle of endothelial dysfunction in COVID-19 [ 37 ]. Complement is a major regulator of endothelial injury syndromes, such as thrombotic microangiopathies [ 38 , 39 ]. Severe COVID-19 appears to resemble complement-mediated thrombotic microangiopathies in both pathophysiology and clinical phenotype [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

Endothelial Dysfunction in COVID-19: Lessons Learned from Coronaviruses

et al. 2020

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Purpose of Review To review current literature on endothelial dysfunction with previous coronaviruses, and present available data on the role of endothelial dysfunction in coronavirus disease-2019 (COVID-19) infection in terms of pathophysiology and clinical phenotype Recent Findings Recent evidence suggests that signs and symptoms of severe COVID-19 infection resemble the clinical phenotype of endothelial dysfunction, implicating mutual pathophysiological pathways. Dysfunction of endothelial cells is believed to mediate a variety of viral infections, including those caused by previous coronaviruses. Experience from previous coronaviruses has triggered hypotheses on the role of endothelial dysfunction in the pathophysiology of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which are currently being tested in preclinical and clinical studies. Summary Endothelial dysfunction is the common denominator of multiple clinical aspects of severe COVID-19 infection that have been problematic for treating physicians. Given the global impact of this pandemic, better understanding of the pathophysiology could significantly affect management of patients.

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Section: Introductionmentioning

confidence: 99%

Endothelial Dysfunction in COVID-19: Lessons Learned from Coronaviruses

et al. 2020

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“…54 Targeting the complement system may also prove to be a successful strategy in some thrombotic conditions. In this regard, an interesting study by Gavriilaki et al 55 analyzed genetic susceptibility in patients with transplant-associated thrombotic microangiopathy, supporting the concept that complement regulatory genes play a role in severe thrombotic complications of bone marrow transplant.…”

Section: Underlying Mechanisms and New Targets Inflammation Thrombosmentioning

confidence: 88%

Thrombosis and Haemostasis 2020 Editors' Choice Papers

2021

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In this Editor's choice, we highlight last year's papers from Thrombosis and Haemostasis as well as from its open access companion journal THOpen, which found most resonance among our readers' community, holding promise for mechanistic understanding and improved clinical management in the fields of Thrombosis and Haemostasis. Building on the research investigations from this undoubtedly memorable year may be particularly useful to overcome the current pandemic situation. As it became apparent that coronavirus disease 2019 (COVID-19) was not merely a pulmonary disease but that thrombosis was a key element involved in its severity and complications, the thrombosis research community deployed intensive research efforts in the hope to optimize treatment and/or prophylaxis as well as to decipher the mechanisms and characteristics of COVID-19 thrombosis as rapidly as possible. Due to the urgency of the pandemic development, it was indeed not surprising that publications relating to COVID-19 received by far the most attention in 2020. Unprecedented Research Efforts for Unprecedented TimesEarly on into the pandemic, Lippi and Favaloro 1 proposed the simple D-dimer test for prognosis of COVID-19 severity in a short T&H report which received particular resonance. By using classic coagulation tests together with point-of-care methods such as whole blood thromboelastometry, Spiezia et al 2 further reported specific coagulation alterations, thereby identifying a state of severe hypercoagulability in COVID-19 patients with acute respiratory failure. The systematic review and meta-analysis from Jin et al 3 described the coagulation abnormalities seen in Chinese patients with COVID-19. Boscolo et al comparatively assessed the values of different coagulation tests between patients admitted to internal medicine department versus intensive care unit. 4 Beyond this hypercoagulation state, Violi et al extensively reviewed how clotting variables behave and impact on the severity of COVID-19 along with potential antithrombotic treatment options in COVID-19. 5 Marchandot et al proposed that haemostatic abnormalities could be used to help stage severity of To help thrombosis specialists, investigators, and funders, a truly multidisciplinary collaborative group of experts in disciplines including cardiovascular diseases, hematology, vascular medicine, pharmacy and pharmacology, pulmonary and critical care medicine, laboratory medicine, and health policy joined efforts to form the Global COVID-19 Thrombosis Collaborative Group. Their position paper 7 comprehensively discussed classical anticoagulants, antiplatelet drugs, and their anti-inflammatory mechanisms and also agents that modulate inflammation and may thus help to mitigate thromboinflammation. While a panel of experts from China and Europe published a consensus statement with practical guidelines for the prevention and treatment of venous thromboembolism (VTE) associated with COVID-19, 8 Grandmaison et al highlighted the benefits of systematic VTE screening in COVID-19 patients. 9...

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“…Findings of complement activation in β-thalassemia major, thrombotic microangiopathies (TMAs), antiphospholipid antibody syndrome, HELLP syndrome and malaria enhance our efforts in understanding complement activation and its role in the pathophysiology of SCD. [15][16][17][18][19][20][21] Our review originated from the aspiration to provide further evidence in the investigation of complement activation in SCD. This regards a summary of current data on complement activation both in steady state and crisis, probable elemental mechanisms of complement activation in the frame of SCD, actions of hydroxyurea, novel therapeutic approaches including indirect involvement in complement activation and novel endeavours of complement inhibition; all under the prism of a clinician's point of view.…”

Section: Introductionmentioning

confidence: 99%

Complement in Sickle Cell Disease: Are We Ready for Prime Time?

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Tampaki

Sakellari

et al. 2021

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Sickle cell disease (SCD) is a widely spread inherited hemoglobinopathy that includes a group of congenital hemolytic anemias, all characterized by the predominance of sickle hemoglobin (HbS). Its features are anemia, predisposal to bacterial infections and complications such as vaso-occlusive crisis (VOC) or delayed hemolytic transfusion reaction (DHTR), which lead to increased rate of morbidity and mortality even in the era of hydroxyurea. The interaction between sickle cells, neutrophils, platelets or endothelial cells in small vessels results in hemolysis and has been considered the disease's main pathophysiological mechanism. Complement activation has been reported in small cohorts of SCD patients, but the governing mechanism has not been fully elucidated. This will be important to predict the patient group that would benefit from complement inhibition. Until now, eculizumab-mediated complement inhibition has shown beneficial effects in DHTR, with limited reports in patients with VOC. In the meantime, several innovative agents are under clinical development Our state-of-the-art review summarizes current data on 1) complement activation in SCD both in steady state and crisis, 2) underlying mechanisms of complement over-activation for the clinician in the context of SCD, 3) actions of hydroxyurea and new therapeutic approaches including indirect involvement in complement activation, and 4) novel paradigms in complement inhibition.

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Pretransplant Genetic Susceptibility: Clinical Relevance in Transplant-Associated Thrombotic Microangiopathy

Cited by 39 publications

References 62 publications

Endothelial Dysfunction in COVID-19: Lessons Learned from Coronaviruses

Endothelial Dysfunction in COVID-19: Lessons Learned from Coronaviruses

Thrombosis and Haemostasis 2020 Editors' Choice Papers

Complement in Sickle Cell Disease: Are We Ready for Prime Time?

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