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Event: 1845

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Coagulation

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Coagulation

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Organ

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term
blood plasma

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
abnormal blood coagulation	blood	occurrence

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
SARS-CoV-2 to thrombosis and DIC	KeyEvent	Shihori Tanabe (send email)	Under development: Not open for comment. Do not cite	Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
Homo sapiens	Homo sapiens	Moderate	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
All life stages	Moderate

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	Moderate

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Coagulation is a process that responds to injury by the rapid formation of a clot. Activation of coagulation factor proteins are involved in coagulation. In the extrinsic pathway, platelets, upon the contact with collagen in the injured blood vessel wall, release thromboxane A2 (TXA2) and adenosine 2 phosphates (ADP), leading to the clot formation. Extravascular tissue factor (TF) binds to plasma factor VIIa (FVIIa) and promotes the activation of FXa. Activated FXa assembles with cofactors FVa and FVIIIa on the surface of aggregated platelets, which lead to generation of thrombin (FIIa). Thrombin catalyzes the production of fibrin (FG) which creates a clot. The binding of prekallikrein and high-molecular weight kininogen activate FXIIa in the intrinsic pathway. Many regulators are involved in coagulation system. Plasmin is one of the modulators required for dissolution of the fibrin clot. Plasmin is activated by tissue plasminogen activator (tPA) and urokinase plasminogen activation (uPA). SERPINs inhibit thrombin, plasmin and tPA. For example, SERPINE1 or plasminogen activator inhibitor-1 (PAI-1) inhibits tPA/uPA and results in hypofibrinolysis [Bernard I,et al. Viruses. 2021; 13(1):29.]. In addition, SERPING1 inhibits FXII, and thus down-regulation of SERPING1 lifts suppression of FXII of the intrinsic coagulation cascade [Garvin et al. eLife 2020;9:e59177]. Protein C, protein S and thrombomodulin degrade FVa and FVIIIa. [Ref. IPA, Coagulation System, version60467501, release date: 2020-11-19]

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Coagulation and inflammatory parameters are measured in COVID-19 patients [Di Nisio et al. 2021]. Coagulation parameters include platelet count, prothrombin time, activated partial thromboplastin time, D-dimer, fibrinogen, antithrombin III [Di Nisio et al. 2021]. These parameters are measured in the blood.

In vitro systems

Whole human blood model for testing the activation of coagulation and complement system, as well as clot formation [Ekstrand-Hammarström, B. et al. Biomaterials 2015, 51, 58-68, Ekdahl, K.N., et al. Nanomedicine: Nanotechnology, Biology and Medicine 2018, 14, 735-744, Ekdahl, K.N., et al. Science and Technology of Advanced Materials, 20:1, 688-698,]

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

The KE is applicable to broad species/life stage/sex.

References

List of the literature that was cited for this KE description. More help

Bernard I, Limonta D, Mahal LK, Hobman TC. Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19. Viruses. 2021; 13(1):29. DOI: https://doi.org/10.3390/v13010029
Garvin et al. A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm. eLife 2020;9:e59177. DOI: https://doi.org/10.7554/eLife.59177
Di Nisio, Marcello et al. Interleukin-6 receptor blockade with subcutaneous tocilizumab improves coagulation activity in patients with COVID-19 European Journal of Internal Medicine, Volume 83, 34 - 38 DOI: https://doi.org/10.1016/j.ejim.2020.10.020
Ekstrand-Hammarström, B.; Hong, J.; Davoodpour, P.; Sandholm, K.; Ekdahl, K.N.; Bucht, A., Nilsson, B. TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations. Biomaterials 2015, 51, 58-68 DOI:https://doi.org/10.1016/j.biomaterials.2015.01.031
Ekdahl, K.N.; Davoodpour, P.; Ekstrand-Hammarström, B.; Fromell, K.; Hamad, O.A.; Hong, J.; Bucht, A.; Mohlin, C.; Seisenbaeva, G.A.; Kessler, V.G., Nilsson, B. Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles. Nanomedicine: Nanotechnology, Biology and Medicine 2018, 14, 735-744 [DOI: https://doi.org/10.1016/j.nano.2017.12.008]
Kristina N Ekdahl, Karin Fromell, Camilla Mohlin, Yuji Teramura & Bo Nilsson (2019) A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity, Science and Technology of Advanced Materials, 20:1, 688-698, DOI: 10.1080/14686996.2019.1625721