New insight into the traditional model of the coagulation cascade and its regulation: illustrated review of a three-dimensional view

Troisi, Romualdo; Balasco, Nicole; Autiero, Ida; Sica, Filomena; Vitagliano, Luigi

doi:10.1016/j.rpth.2023.102160

Cited by 4 publications

(2 citation statements)

References 59 publications

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“…On monocytes, P-selectin binding rapidly exposes tissue factor (TF), the coagulation initiator, to the surface [ 29 , 30 , 31 , 32 , 33 , 34 ]. Over time, the expression of the TF gene increases and TF is released from the surface of monocytes in extracellular vesicles.…”

Section: Understanding the Role Of Platelets And P-selectin As Key Ac...mentioning

confidence: 99%

“…These processes, along with platelet aggregation and fibrin deposition, can cause vascular occlusion even without physical injury to the blood vessels. Platelets also act as protectors by preventing bleeding On monocytes, P-selectin binding rapidly exposes tissue factor (TF), the coagulation initiator, to the surface [29][30][31][32][33][34]. Over time, the expression of the TF gene increases and TF is released from the surface of monocytes in extracellular vesicles.…”

Section: Understanding the Role Of Platelets And P-selectin As Key Ac...mentioning

confidence: 99%

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To Gain Insights into the Pathophysiological Mechanisms of the Thrombo-Inflammatory Process in the Atherosclerotic Plaque

Nappi

2023

IJMS

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Thromboinflammation, the interplay between thrombosis and inflammation, is a significant pathway that drives cardiovascular and autoimmune diseases, as well as COVID-19. SARS-CoV-2 causes inflammation and blood clotting issues. Innate immune cells have emerged as key modulators of this process. Neutrophils, the most predominant white blood cells in humans, are strategically positioned to promote thromboinflammation. By releasing decondensed chromatin structures called neutrophil extracellular traps (NETs), neutrophils can initiate an organised cell death pathway. These structures are adorned with histones, cytoplasmic and granular proteins, and have cytotoxic, immunogenic, and prothrombotic effects that can hasten disease progression. Protein arginine deiminase 4 (PAD4) catalyses the citrullination of histones and is involved in the release of extracellular DNA (NETosis). The neutrophil inflammasome is also required for this process. Understanding the link between the immunological function of neutrophils and the procoagulant and proinflammatory activities of monocytes and platelets is important in understanding thromboinflammation. This text discusses how vascular blockages occur in thromboinflammation due to the interaction between neutrophil extracellular traps and ultra-large VWF (von Willebrand Factor). The activity of PAD4 is important for understanding the processes that drive thromboinflammation by linking the immunological function of neutrophils with the procoagulant and proinflammatory activities of monocytes and platelets. This article reviews how vaso-occlusive events in thrombo-inflammation occur through the interaction of neutrophil extracellular traps with von Willebrand factor. It highlights the relevance of PAD4 in neutrophil inflammasome assembly and neutrophil extracellular traps in thrombo-inflammatory diseases such as atherosclerosis and cardiovascular disease. Interaction between platelets, VWF, NETs and inflammasomes is critical for the progression of thromboinflammation in several diseases and was recently shown to be active in COVID-19.

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Section: Understanding the Role Of Platelets And P-selectin As Key Ac...mentioning

confidence: 99%

Section: Understanding the Role Of Platelets And P-selectin As Key Ac...mentioning

confidence: 99%

To Gain Insights into the Pathophysiological Mechanisms of the Thrombo-Inflammatory Process in the Atherosclerotic Plaque

Nappi

2023

IJMS

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Structural overview of DNA and RNA G-quadruplexes in their interaction with proteins

Troisi,

Sica

2024

Current Opinion in Structural Biology

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Fourteen Deaths from Suspected Heparin Overdose in an Italian Primary-Level Hospital

Di Fazio,

Scopetti,

Delogu

et al. 2023

Diagnostics

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Healthcare-related homicidal cases are not novel within the medical–legal landscape, but investigations are often made difficult with the scarcity of material evidence related to the crime. For this reason, it is necessary to carefully analyze the clinical documentation and employ ancillary forensic resources such as radiology, histopathology, and toxicology. In the presented scenario, the observation of 14 deaths from abnormal bleeding in a First-Level Italian Hospital revealed the administration of massive doses of heparin by a nurse. On behalf of the Judicial Authority, a multidisciplinary medical team investigated the case through the following steps: a thorough review of the clinical documentation, exhumation of the bodies belonging to the deceased patients, performing PMCT and autopsy, and collecting tissue samples for histopathological, immunohistochemical, and toxicological investigations. All the analyzed cases have been characterized by the observation of fatal hemorrhagic episodes not explained with the clinical conditions of the patients, confirmed using autopsy observations and the histological demonstration of the vitality of the lesions. However, due to the limited availability of biological material for the toxicological analysis, the indirect evidence from hematological analyses in hospitalized patients was crucial in demonstrating heparin overdose and its link to the recorded deaths. The present scenario demonstrates the fundamental importance of a multidisciplinary approach to cases of judicial interest related to the healthcare context. Therefore, the illustrated methodologies can be interpreted as an operational framework for similar future cases.

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New insight into the traditional model of the coagulation cascade and its regulation: illustrated review of a three-dimensional view

Cited by 4 publications

References 59 publications

To Gain Insights into the Pathophysiological Mechanisms of the Thrombo-Inflammatory Process in the Atherosclerotic Plaque

To Gain Insights into the Pathophysiological Mechanisms of the Thrombo-Inflammatory Process in the Atherosclerotic Plaque

Structural overview of DNA and RNA G-quadruplexes in their interaction with proteins

Fourteen Deaths from Suspected Heparin Overdose in an Italian Primary-Level Hospital

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