coagulation activity
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Author(s):  
Revathi Raman ◽  
Weam Fallatah ◽  
Ayah Al Qaryoute ◽  
Mia Ryon ◽  
Pudur Jagadeeswaran

Tissue Factor Pathway Inhibitor (TFPI) is an anticoagulant that inhibits factor VIIa and Xa in the blood coagulation pathways. TFPI contains three Kunitz domains, K1, K2, and K3. K1 and K2 inhibit factor VIIa and Xa, respectively. However, the regulation of TFPI is poorly studied. Since zebrafish has become an alternate model to discover novel actors in hemostasis, we hypothesized that TFPI regulation could be studied using this model. As a first step, we confirmed the presence of tfpia in zebrafish using RT-PCR. We then performed piggyback knockdowns of tfpia and found increased coagulation activity in tfpia knockdown. We then created a deletion mutation in tfpia locus using CRISPR/Cas9 method. The tfpia homozygous deletion mutants showed increased coagulation activities similar to that found in tfpia knockdown. Taken together, our data suggest that tfpia is a negative regulator for zebrafish coagulation, and silencing it leads to thrombotic phenotype. Also, the zebrafish tfpia knockout model could be used for reversing this thrombotic phenotype to identify antithrombotic novel factors by the genome-wide piggyback knockdown method.


2021 ◽  
Vol 13 (4) ◽  
pp. 352-356
Author(s):  
T. Angelova ◽  
J. Krastanov ◽  
D. Yordanova

Abstract. The aim of the present study was to evaluate allele frequencies and genotypes of kappa casein (CSN3) and their association with milk quality and coagulation properties in Brown cattle. Milk proteins’ polymorphism was found out in 155 tissue samples from cows reared at 4 farms. The analysis of milk composition was done in the lab of the Agriculture Institute – Stara Zagora on Lactoscan ultrasound milk analyzer, whereas coagulation properties of individual milk samples were evaluated on a Computerized Renneting Metter – Polo Trade, Italy. Milk samples were obtained by milk meters. The milk was analysed within 3 hours after sample collection. Naturen Plus 215/0.8L chymosin was used, with milk coagulation activity of 215 IMCU/ml. During the study, the following parameters were studied: milk fat and protein contents (%), rennet coagulation time (RCT, min), curd firmness (а30, mm) and curd firming time (k20, min). Kappa casein (CSN3) is characterised by five genotypes – АА, АВ, ВВ, АН and ВН, the frequency of which varied within various ranges. The milk of cows with genotype AB was characterized by the highest content of fat and protein: 4.85% and 5.00%, respectively. The milk of heterozygous cows from genotype AB demonstrated the longest rennet coagulation time – 18.04 min. The animals carrying the H allele produced milk with the highest curd firmness – 37.00 mm.


2021 ◽  
Vol 33 (4) ◽  
pp. 57-66
Author(s):  
Carmela Tripaldi ◽  
Giuliano Palocci ◽  
Sabrina Di Giovanni ◽  
Miriam Iacurto ◽  
Roberto Steri ◽  
...  

In the production of some traditional cheeses from vegetable rennet, raw extracts of Cynara cardunculus flowers are used as the coagulant. During the preparation of this rennet, there are many factors that can influence its coagulation activity. We studied the flowers of Cynara cardunculus var. altilis to evaluate the effects of some of these factors: ripening stage of the flower at harvest, type of drying, part of the flower subjected to drying, toasting of the pistils, and maceration time of the pistils. The results show that it is possible to improve the coagulation activity of the traditional preparation of Cynara cardunculus flowers through some practices such as the rapid drying of the flowers/pistils at a controlled temperature, the toasting treatment of the pistils carried out after the slow drying of the flowers, and the extension of the extraction time to 24 h.


Author(s):  
Maximilian Winzely ◽  
Annukka Jouppila ◽  
Georg Ramer ◽  
Laurin Lux ◽  
Bernhard Lendl ◽  
...  

Abstract Antiplatelet and anticoagulant drugs are classified antithrombotic agents with the purpose to reduce blood clot formation. For a successful treatment of many known complex cardiovascular diseases driven by platelet and/or coagulation activity, the need of more than one antithrombotic agent is inevitable. However, combining drugs with different mechanisms of action enhances risk of bleeding. Dual anticoagulant and antiplatelet (APAC), a novel semisynthetic antithrombotic molecule, provides both anticoagulant and antiplatelet properties in preclinical studies. APAC is entering clinical studies with this new exciting approach to manage cardiovascular diseases. For a better understanding of the biological function of APAC, comprehensive knowledge of its structure is essential. In this study, atomic force microscopy (AFM) was used to characterize APAC according to its structure and to investigate the molecular interaction of APAC with von Willebrand factor (VWF), since specific binding of APAC to VWF could reduce platelet accumulation at vascular injury sites. By the optimization of drop-casting experiments, we were able to determine the volume of an individual APAC molecule at around 600 nm3, and confirm that APAC forms multimers, especially dimers and trimers under the experimental conditions. By studying the drop-casting behavior of APAC and VWF individually, we depictured their interaction by using an indirect approach. Moreover, in vitro and in vivo conducted experiments in pigs supported the AFM results further. Finally, the successful adsorption of APAC to a flat gold surface was confirmed by using photothermal-induced resonance, whereby attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) served as a reference method. Graphical abstract


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 293-293
Author(s):  
Magdolna Nagy ◽  
Alejandro Pallares Robbles ◽  
Mayken Visser ◽  
Vincent Ten Cate ◽  
Thomas Knoeck ◽  
...  

Abstract Venous thromboembolism (VTE) is associated with increased coagulation activity, which in part can be attributed to the contact pathway of coagulation. Evidence from pre-clinical and epidemiological studies suggests that deficiency in factors of contact activation (e.g. coagulation factors (F) XI and FXII) protects against VTE. However, limited information exists regarding the activation of the contact system in the setting of acute VTE. In the current study, patients with confirmed VTE events (n=321) from the VTEval study and controls (n=300) from the population-based PREVENT-it pilot study were included. Plasma samples were collected from patients after confirmed VTE events or controls upon inclusion in the study. FXI as well as FXIa and plasma kallikrein (PKa) levels were assessed in plasma samples from all subjects using an activated thromboplastin time-based assay (FXI:c), a thrombin generation-based assay (CAT:FXIa) and by measuring inhibitory complexes (FXIa:antithrombin (AT), FXIa:alpha-1-antitrypsin (α1AT), FXIa:C1 esterase inhibitor (C1Inh) and PKa:C1Inh) using enzyme-linked immunoassay (ELISA). After a 2-year follow up period, a composite endpoint of recurrent VTE or death was determined. Increased FXI:c levels were determined in VTE patients compared to control individuals (124.08 ± 37.48% vs. 113.55 ± 27.99%), whereas CAT:FXIa levels were reduced in VTE patients (0 pM [IQR, 0-0.56] vs 0.56 pM [IQR, 0-0.88]). Levels of FXIa:α1AT and FXIa:AT inhibitory complexes were increased in VTE patients compared to controls (median[IQR]; 311.8 pM [238.2-424.0] vs. 202.5 pM [143.7 - 287.5] and 29.1 pM [23.4-38.3] vs 23.2 pM [19.7-29.8], respectively). Considering that 86% of the VTE patients were already on anticoagulant treatment (Table 1), investigation of their possible effect on the biomarkers revealed that only the CAT:FXIa was influenced by the presence of anticoagulants. Logistic regression models revealed a good discriminatory value for FXI:c and FXIa:α1AT (AUC=0.64 [0.6/0.69] and AUC=0.67 [0.62/0.71], respectively) to distinguish VTE from controls, whereas the other biomarkers were not able to distinguish between groups. The outcome recurrent VTE or death could be predicted by the inhibitory complexes, but not by the FXI(a) levels (Figure 1). Only the FXIa:α1AT complexes were able to both detect the presence of VTE (OR per SD [95%CI]: 1.28 [1.01-1.63], p=0.04) and predict recurrent VTE or death (HR per SD [95%CI]: 1.40 [1.2-1.62], p<0.0001). In summary, acute VTE is associated with both elevated FXI:c levels and increased activation of FXI and plasma prekallikrein, the latter specifically indicating contact activation. The generation of FXIa during acute VTE and its association with recurrent VTE suggests an important risk contribution of FXI activation. This study has added evidence favouring the utility of FXIa inhibition in the setting of acute VTE. Figure 1 Figure 1. Disclosures Knoeck: Bayer AG: Consultancy. ten Cate: Bayer AG: Other; Pfizer: Other; LEO Pharma: Other; Gideon Pharmaceuticals: Other; Alveron Pharma: Other. Wild: Bayer AG: Other, Research Funding; Boehringer Ingelheim: Other, Research Funding; Novartis Pharma: Other, Research Funding; Sanofi-Aventis: Other, Research Funding; Astra Zeneca: Other, Research Funding; Daiichi Sankyo Europe: Other, Research Funding.


2021 ◽  
Vol 5 (3) ◽  
pp. 403-415
Author(s):  
Muso Urinov ◽  
Nigora Alikulova ◽  
Dilfuza Zukhritdinova ◽  
Mekhriddin Usmonov ◽  
Rakhimjon Urinov

280 patients with COVID-19 were examined (average age 53.9±8.1 years; gender index 1.37:1.0 (162 men and 118 women). It was revealed that young people (especially women) were more common with a mild course of the disease (64.2%), middle – aged people-with a moderate-severe variant of COVID-19 (54.8%), In the group of patients with a severe course of coronavirus infection, female patients prevailed among the elderly, and among middle –aged men – 47.8% and 48.4%, respectively. The comorbid background before the disease CAVID-19 and the neurological complications that appeared on the background of CAVID-19 in the percentage ratio prevailed in males. There were no significant differences in the frequency of complications from the severity of the COVID-19 disease. It was revealed that at the time of hospitalization, all the studied markers of coagulation activity were changed and statistically significantly differed from the reference interval, which indicated the activation of the procoagulation potential. In the group of female patients, these indicators were more pronounced. CT examination revealed that the percentage of damage to both lungs was significantly higher in female patients compared to male patients.


2021 ◽  
Vol 4 (2) ◽  
pp. 124
Author(s):  
Victor Perdana Kusuma ◽  
Deasy Ardiany

Introduction: Coronavirus Disease 2019 (COVID-19) is a respiratory tract infection caused by the SARS-CoV-2 virus, which was announced a pandemic by the World Health Organization (WHO) on March 11, 2020. On March 2, 2020, two confirmed cases of COVID-19 were initially reported in Indonesia. COVID-19 has been reported in 96.2 million people around the world. COVID-19 has already stolen the lives of almost 2 million individuals. Diabetes mellitus patients face an additional challenge with this disease (DM). Several studies have found a link between diabetes mellitus and COVID-19, as well as a bad prognosis for persons with DM and COVID-19. Aim of this study was to learn more about the link between diabetes and COVID-19, as well as the pathophysiology of diabetes.Methods: We searched for articles in PubMed and Google Scholar databases till February 2021, with the following keywords: “SARS-CoV-2”, “COVID-19”, “infection”, “pathogenesis”, “diabetes”Results: Diabetes Mellitus increased the severity and mortality of COVID-19 patients due to mechanisms involving inflammation and immune system activation, increased coagulation activity, oxidative stress, glucotoxicity, endoplasmic reticulum stress, renin-angiotensin-aldosterone system disorders, apoptotic mechanisms, mitochondrial dysfunction, and damage to pancreatic beta cells. COVID-19 infection can also lead to hyperglycemia and new-onset diabetes.Conlusion: Diabetes Mellitus is one of the comorbidities linked to a worse COVID-19 prognosis, according to the findings of this literature study. Furthermore, current research suggests that COVID-19 might cause hyperglycemia or new-onset diabetes, which has a poorer prognosis than COVID-19 patients with pre-existing diabetes.


Author(s):  
Abdulmajeed Alharbi ◽  
Neha Iyer ◽  
Ayah AlQaryoute ◽  
Revathi Raman ◽  
David Burks ◽  
...  

Hemolytic disorders are characterized by hemolysis and are prone to thrombosis. Previously, it has been shown that the RNA released from damaged blood cells activates clotting. However, the nature of RNA released from hemolysis is still elusive. We found that after hemolysis, RBCs from both zebrafish and humans released 5.8S rRNA. This RNA activated coagulation in zebrafish and human plasmas. Using both natural and synthetic 5.8S rRNA and its truncated fragments, we found that the 3'-end 26 nucleotide-long RNA (3'-26 RNA) and its stem-loop secondary structure were necessary and sufficient for clotting activity. Corn trypsin inhibitor (CTI), a coagulation factor XII (FXII) inhibitor blocked 3'-26 RNA-mediated coagulation activation of both zebrafish and human plasma. CTI also inhibited zebrafish coagulation in vivo. 5.8S rRNA monoclonal antibody inhibited both 5.8S rRNA- and 3'-26 RNA-mediated zebrafish coagulation activity. Both 5.8S rRNA and 3'-26 RNA activates normal human plasma but did not activate FXII-deficient human plasma. Taken together, these results suggested that the activation of zebrafish plasma is via FXII-like protein. Since zebrafish has no FXII and hepatocyte growth factor activator (Hgfac) has sequence similarities to FXII, we knocked down the hgfac in adult zebrafish. We found that plasma from this knockdown fish does not respond to 3'-26 RNA. In conclusion, we identified 5.8S rRNA released in hemolysis activates clotting in human and zebrafish plasma. Only 3'-end 26 nucleotides of the 5.8S rRNA is needed for the clotting activity. Furthermore, we showed that fish Hgfac plays a role in 5.8S rRNA-mediated activation of coagulation.


Cureus ◽  
2021 ◽  
Author(s):  
Abhishek Goyal ◽  
Puneet Aggarwal ◽  
Abhinav Shrivastava ◽  
Bhagya Narayan Pandit ◽  
Saibal Mukhopadhyay ◽  
...  

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