Thromboinflammation in Sepsis and Heparin: A Review of Literature and Pathophysiology.

BACKGROUND/AIM: Thromboinflammation is the pathophysiologic mechanism in which coagulation and inflammation interact and complement each other. It is observed in a number of degenerative diseases, one of them being sepsis. Quiescent endothelial cells exert antithrombotic and anti-inflammatory actions that are reduced during sepsis. The concomitant effect of the subsequent dysregulation of coagulation and complement actuation is platelet activation and aggregation, and leukocyte recruitment, with detrimental effects on the vascular endothelium. Tissue factor and α-thrombin are major sentinels in the pathogenesis of this process. This literature review aimed to cover the basic principles of the mechanisms implicated in thromboinflammation occurring during sepsis and also investigates the role of heparin as a possible therapeutic agent, since it exhibits both anticoagulant and anti-inflammatory functions. MATERIALS AND METHODS: PubMed, SCOPUS and ScienceDirect databases were used for search of literature from inception to April 2022. To be included in our review, studies had to refer to the pathophysiologic mechanisms leading to coincident coagulation and inflammation, or to the administration of heparin either for treatment or prophylaxis, both in the context of sepsis. RESULTS: A total of 276 articles were drawn from the initial literature search. 124 were duplicated and out of the remaining 152 articles, 29 met our inclusion criteria and were reviewed. CONCLUSION: Clinical trials among sepsis patients have indicated that the thromboinflammatory process is more complex than believed, as adverse bleeding events continue to occur despite the use of anticoagulants with different pharmacodynamics. However, heparin has a pleiotropic effect that might provide protection against sepsis and related complications and merits further research.

Recent advances in understanding and managing sepsis.

The last two to three years provided several "big steps" regarding our understanding and management of sepsis. The increasing insight into pathomechanisms of post-infectious defense led to some new models of host response. Besides hyper-, hypo-, and anti-inflammation as the traditional approaches to sepsis pathophysiology, tolerance and resilience were described as natural ways that organisms react to microbes. In parallel, huge data analyses confirmed these research insights with a new way to define sepsis and septic shock (called "Sepsis-3"), which led to discussions within the scientific community. In addition to these advances in understanding and defining the disease, follow-up protocols of the initial "sepsis bundles" from the Surviving Sepsis Campaign were created; some of them were part of quality management studies by clinicians, and some were in the form of mandatory procedures. As a result, new "bundles" were initiated with the goal of enabling standardized management of sepsis and septic shock, especially in the very early phase. This short commentary provides a brief overview of these two major fields as recent hallmarks of sepsis research.

Recent advances in pathophysiology and biomarkers of sepsis-induced acute kidney injury.

Sepsis is a complex clinical syndrome characterized by a systemic inflammatory response to an infective insult. This process often leads to widespread tissue injury and multiple organ dysfunction. In particular, the development of acute kidney injury (AKI) is one of the most frequent complications, which increases the complexity and cost of care, and is an independent risk factor for mortality. Previous suggestions highlighting systemic hypotension, renal vasoconstriction and ischaemia-reperfusion injury as the primary pathophysiological mechanisms involved in sepsis-induced AKI have been challenged. Recently it has been shown that sepsis-induced AKI occurs in the setting of microvascular dysfunction with release of microparticles, inflammation and energetic adaptation of highly metabolic organs to cellular stress. The intolerable high mortality rate associated with sepsis-induced AKI is partially explained by an incomplete understanding of its pathophysiology and a delay in diagnosis. The aim of this review is to focus on advances in understanding the sepsis pathophysiology, with particular attention to the fundamental mechanisms of sepsis-induced AKI and the potential diagnostic and prognostic markers involved.

Sepse: atualidades e perspectivas / Sepsis: an update

O objetivo do presente artigo é oferecer uma atualização dos principais aspectos da sepse, complicação infecciosa extremamente importante do ponto de vista da clínica e da saúde pública. Algumas hipóteses têm sido propostas para explicar sua gênese, as quais encerram aspectos referentes a interação microrganismo/sistema imune inato, a inflamação/mediação imunológica e o sistema de coagulação. As manifestações clínicas são variadas e dependem do local primário da infecção. A identificação precoce dos sinais e sintomas é de crucial importância para a instituição de medidas terapêuticas que se baseiam, fundamentalmente, em reposição volêmica, antibioticoterapia, emprego de costicosteróides, tratamento anticoagulante, medidas de manutenção da viabilidade biológica e suporte nutricional.

This paper aims to provide an update on the main aspects of sepsis, a very relevant health care issue. A number of hypotheses have been proposed to explain its origin, involving interactions between microorganisms and the innate immune system, inflammation/immune mediation and the coagulation system. The clinical features of sepsis are variable and depend on the primary site of infection. The identification of early signs and symptoms is crucial for starting therapeutic measures fundamentally based on volume resuscitation, antibiotic therapy, use of steroids, anticoagulant therapy, biologic viability maintenance interventions and nutritional support.