Coagulation Cascade
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Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 782
Alexander A. Osmolovskiy ◽  
Laura Schmidt ◽  
Anastasia V. Orekhova ◽  
Sergey K. Komarevtsev ◽  
Valeriana G. Kreyer ◽  

In this study, we investigated the properties of proteolytic enzymes of two species of Aspergillus, Aspergillus flavus 1 (with a high degree of pathogenicity) and Aspergillus ochraceus L-1 (a conditional pathogen), and their effects on various components of the hemostasis system (in vitro) in the case of their penetration into the bloodstream. We showed that micromycete proteases were highly active in cleaving both globular (albuminolysis) and fibrillar (fibrin) proteins, and, to varying degrees, they could coagulate the plasma of humans and animals (due to proteolysis of factors of the blood coagulation cascade) but were not able to coagulate fibrinogen. The proteases of both Aspergillus fully hydrolyzed thrombi in 120–180 min. Micromycetes did not show hemolytic activity but were able to break down hemoglobin.

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 776
Fahimeh Faqihi ◽  
Marcus A. Stoodley ◽  
Lucinda S. McRobb

In cardiovascular and cerebrovascular biology, control of thrombosis and the coagulation cascade in ischemic stroke, myocardial infarction, and other coagulopathies is the focus of significant research around the world. Ischemic stroke remains one of the largest causes of death and disability in developed countries. Preventing thrombosis and protecting vessel patency is the primary goal. However, utilization of the body’s natural coagulation cascades as an approach for targeted destruction of abnormal, disease-associated vessels and tissues has been increasing over the last 30 years. This vascular targeting approach, often termed “vascular infarction”, describes the deliberate, targeted delivery of a thrombogenic effector to diseased blood vessels with the aim to induce localized activation of the coagulation cascade and stable thrombus formation, leading to vessel occlusion and ablation. As systemic delivery of pro-thrombotic agents may cause consternation amongst traditional stroke researchers, proponents of the approach must suitably establish both efficacy and safety to take this field forward. In this review, we describe the evolution of this field and, with a focus on thrombogenic effectors, summarize the current literature with respect to emerging trends in “coaguligand” development, in targeted tumor vessel destruction, and in expansion of the approach to the treatment of brain vascular malformations.

2021 ◽  
Vol 2021 (2) ◽  
Szu S. Wong

Coagulation as a process is interpreted as a mechanism for reducing excessive blood loss through the generation of a gel-like clot local to the site of injury. The process involves the activation, adhesion (see Integrins), degranulation and aggregation of platelets, as well as proteins circulating in the plasma. The coagulation cascade involves multiple proteins being converted to more active forms from less active precursors (for example, prothrombin [Factor II] is converted to thrombin [Factor IIa]), typically through proteolysis (see Proteases). Listed here are the components of the coagulation cascade targeted by agents in current clinical usage or at an advanced level of development.

2021 ◽  
Vol 12 ◽  
Yue Li ◽  
Qiang Wen ◽  
Huaisheng Chen ◽  
Xinhui Wu ◽  
Bin Liu ◽  

The pathological mechanism underlying heat stroke (HS) is associated with the dysbalanced inflammation and coagulation cascade. Cell-derived circulating extracellular vesicles (EVs), as a novel pathway mediating intercellular communication, are associated with the immune response and inflammation in critical inflammatory syndromes, such as sepsis. Although these vesicles contain genetic material correlated with their biological function, their molecular cargo during HS remains unknown. In this study, we evaluate the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) associated with inflammatory responses and coagulation cascade in exosomes of patients with HS. Blood samples were collected from three patients with HS at the time of admission to the intensive care unit; three healthy volunteers were selected as control. Exosomes were isolated using ultracentrifugation, and their miRNA content was profiled using next-generation sequencing; mRNA content was evaluated using qPCR array. Compared with those from healthy volunteers, exosomes from patients with HS showed substantial changes in the expression of 202 exosomal miRNAs (154 upregulated and 48 downregulated miRNAs). The most upregulated miRNAs included miR-511-3p, miR-122-5p, miR-155-3p, miR-1290, and let7-5p, whereas the most downregulated ones included miR-150-3p, 146a-5p, and 151a-3p. Gene ontology enrichment of the miRNAs of patients with HS compared with control subjects were associated mostly with inflammatory response, including T cell activation, B cell receptor signaling, dendritic cell chemotaxis and leukocyte migration, and platelet activation and blood coagulation. The identified miRNAs were primarily enriched to the signal transduction pathways namely, T cell receptor signaling, Ras signaling, chemokine signaling, platelet activation, and leukocyte transendothelial migration, all of which are associated with inflammation and hemostasis. Multiple targeted mRNAs associated with the inflammatory response, blood coagulation, and platelet activation were further verified in serum exosomes. Exosomes from patients with HS convey miRNAs and mRNAs associated with pathogenic pathways, including inflammatory response and coagulation cascade. Exosomes may represent a novel mechanism for intercellular communication during HS.

2021 ◽  
Vol 8 (1) ◽  
Bhandary R ◽  
Poojitha S ◽  

Lingual hematoma is a rare cause of airway compromise and is usually seen secondary to use of anticoagulants, which exerts effects on coagulation cascade, and also causes thrombocytopenia. The patient in this case report presents with a lingual hematoma which is not related to the use of any anticoagulants. Luckily, the hematoma did not enlarge enough to cause obstruction of airway requiring tracheotomy. However, the cause of the hematoma is deduced to be due to husk - injuring the tongue mucosa. This case is unique in its rare presentation as well as the cause for the hematoma in our report has never been reported in literature.

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
S Grigoryan ◽  
LG Hazarapetyan ◽  
AA Stepanyan ◽  
DM Andreasyan

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Atrial fibrillation (AF) is a highly prevalent  problem that is becoming more common with population aging  and  has many complication. The most significant complication of AF is thromboembolism, particularly stroke, because AF  produces a hypercoagulable state and provokes pro-fibrotic, pro-hypertrophic, and pro-inflammatory responses in a variety of tissues. Various inflammation markers such as interleukin-6 (IL-6) and high sensitivy C-reactive protein (hsCRP) have been linked with AF. Several prothrombotic factors have been found to be elevated in AF, which contributed to an increased risk for stroke.The tissue factor (TF) as a principal initiator of the coagulation cascade. The aim of this study is to investigate the relationship between inflammation markers and risk of dynamic cerebrovascular accident or stroke, including the impact of this interaction on the outcome in patients with AF Methods. We observed 441 patients with nonvalvular AF during 5 years (2010-2016). Clinical examination of patients included a study of complaints (especially HF, dynamic cerebrovascular accident and stroke), physical, laboratory and instrumental examination, also additional biochemical blood tests , such as TF, hsCRP and IL-6. The blood tests were determined by ELISA on the analyzer "Stat Fax 303 Plus".  Treatment regimens carried out in all patients included standard therapy, which is held in the hospital for the treatment of AF.  Studies were conducted on the basis of simple randomized open-label protocols, using the universal statistical packages SPSS 13.0 Results Obtained results have shown that among 441 patients with AF within 5 years, heart failure was detected in 257 patients, 116 had either a cerebral circulation disorder or a stroke. It was found that in patients undergoing dynamic cerebrovascular accident or stroke there was a significant increase in levels of inflammatory markers compared with other patients with AF. So, the significant differences between the levels of hsCRP are 6, 7± 1.8 vs. 3.2 ± 0.6 p = 0.002 and level of IL-6 is 4.2± 0.8 vs.  2.6± 1.1 p = 0.043 accordingly. We revealed also that in patients with dynamic cerebrovascular accident or stroke the level of TF is improved as compared the other patients with AF (1200± 50.vs 850 ± 31.9 p = 0.026). Moreover plasma levels of hsCRP were higher among AF patients at high risk of stroke (=3 or more) by CHA2DS2-VASc (p = 0.003).  Besides the levels of hsCRP and IL-6 are markedly elevated in patients with dilated left atrium, poorly functioning left atrial appendage and ventricular dysfunction .The similar tendency of hsCRP, IL-6 and TF was also observed in patients with AF and heart failure. Conclusion we have demonstrated that inflammation markers such as hsCRP and IL-6, together with coagulation cascade markers, are additional prognostic criteria that contribute to the development of dynamic cerebral circulation disorders or stroke in patients with AF

2021 ◽  
Alexandre Ranc ◽  
Salome Bru ◽  
Simon Mendez ◽  
Muriel Giansily-Blaizot ◽  
Franck Nicoud ◽  

Computational models of the coagulation cascade are used for a wide range of applications in bio-medical engineering such as drug and bio-medical device developments. However, a lack of robustness of numerical models has been highlighted when studying clinically relevant scenarios. In order to develop more robust models, numerical simulations need to be confronted with realistic situations relevant to clinical practice. In this work, two well-established numerical representations of the coagulation cascade initiated by the intrinsic and extrinsic systems, respectively, were compared with thrombin generation assays considering realistic pathological conditions. Proper modifications were needed to align the in vitro and in silico data, namely; adapting initial conditions to the thrombin assay system, omitting reactions irrelevant to our case study, and improving the fitting of some reaction rates. The modified models were able to capture the experimental trends of thrombin generation for a range of concentrations of factors XII, XI, and VIII for cases in which the coagulation cascade is triggered through the extrinsic and intrinsic systems. Our work emphasizes that when existing coagulation cascade models are extrapolated to experimental settings for which they were not calibrated, careful adjustments must be made. We show that the two coagulation models used in this work can predict physiological conditions, but when studying pathological conditions, proper modifications are needed to improve the numerical results.

2021 ◽  
Vol 20 (1) ◽  
Mark P. Ward ◽  
Laura E. Kane ◽  
Lucy A. Norris ◽  
Bashir M. Mohamed ◽  
Tanya Kelly ◽  

AbstractCancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using “liquid biopsies” to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1487
Lena Hell ◽  
Thomas Däullary ◽  
Vanessa Burghart ◽  
Lisa-Marie Mauracher ◽  
Ella Grilz ◽  

Patients with advanced prostate cancer may develop fulminant disseminated intravascular coagulation (DIC). Circulating extracellular vesicles (EVs)-exposing tissue factor (TF), the initiator of the coagulation cascade, may play an important role. We included 7 prostate cancer patients with DIC, 10 age- and stage-matched cancer controls without DIC, and 10 age-matched healthy male individuals. EV-TF activity was highly elevated in prostate cancer patients with DIC (11.40 pg/mL; range: 4.34–27.06) compared with prostate cancer patients without DIC (0.09 pg/mL; range: 0.00–0.30, p = 0.001) and healthy controls (0.18 pg/mL; range: 0.09–0.54; p = 0.001). Only EVs from patients with DIC showed reduced fibrin clot formation time of pooled plasma in a TF-dependent manner. Next, we performed in vitro co-culture experiments including EVs derived from a prostate cancer cell line with high (DU145) and low (LNCaP) TF expression, peripheral blood mononuclear cells (PBMCs), and platelets. Co-incubation of DU145 EVs with PBMCs and platelets significantly increased EV-TF activity in conditioned medium and induced TF activity on monocytes. No such effects were seen in co-culture experiments with LNCaP EVs. In conclusion, the findings indicate that elevated EV-TF activity plays a role in the development of prostate-cancer-related DIC and may result from interactions between tumor-derived EVs, monocytes, and platelets.

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