Status
This is a legacy representation of this AOP. Please see the current version here:
https://aopwiki.org/aops/187
AOP Title
Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage
Short name: VKOR inhibition resulting in coagulopathy
Authors
Status
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This AOP page was last modified on 12/11/2016.
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Abstract
Background (optional)
Summary of the AOP
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Molecular Initiating Event
Key Events
Event
|
Support for Essentiality
|
Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) , Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X |
Strong
|
Depletion from blood of fully functional carboxylated clotting factors, Hemostasis |
Strong
|
Failure of secondary hemostasis , Under carboxylated clotting factors will not assemble on cell surfaces to form clot |
Strong
|
Unresolved blood loss (hemorrhage), Failure in vascular repair mechanisms |
Moderate
|
Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal, Blood loss and development of anemia |
Strong
|
Acidosis, hypovolemic shock and organ dysfunction, Reduced fitness or even mortality |
Strong
|
Bone deterioration, Osteoporosis and vascular calcification |
Moderate
|
Adverse Outcome
Relationships Among Key Events and the Adverse Outcome
Event
|
Description
|
Triggers
|
Weight of Evidence
|
Quantitative Understanding
|
Depletion from blood of fully functional carboxylated clotting factors, Hemostasis |
Directly Leads to |
Failure of secondary hemostasis , Under carboxylated clotting factors will not assemble on cell surfaces to form clot |
Strong |
Strong
|
Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone, Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139 |
Directly Leads to |
Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) , Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X |
Strong |
Strong
|
Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) , Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X |
Indirectly Leads to |
Depletion from blood of fully functional carboxylated clotting factors, Hemostasis |
Strong |
Strong
|
Failure of secondary hemostasis , Under carboxylated clotting factors will not assemble on cell surfaces to form clot |
Directly Leads to |
Unresolved blood loss (hemorrhage), Failure in vascular repair mechanisms |
Strong |
Strong
|
Unresolved blood loss (hemorrhage), Failure in vascular repair mechanisms |
Directly Leads to |
Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal, Blood loss and development of anemia |
Strong |
Strong
|
Acidosis, hypovolemic shock and organ dysfunction, Reduced fitness or even mortality |
Indirectly Leads to |
Population trajectory, Impaired recruitment |
Weak |
Weak
|
Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal, Blood loss and development of anemia |
Indirectly Leads to |
Acidosis, hypovolemic shock and organ dysfunction, Reduced fitness or even mortality |
Moderate |
Strong
|
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Life Stage Applicability
Life Stage
|
Evidence
|
Links
|
all life stages |
Strong |
|
Taxonomic Applicability
Sex Applicability
Sex
|
Evidence
|
Links
|
Male |
|
|
Female |
|
|
Graphical Representation
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Overall Assessment of the AOP
Domain of Applicability
Life Stage Applicability,
Taxonomic Applicability,
Sex Applicability
Elaborate on the domains of applicability listed in the summary section above. Specifically, provide the literature supporting, or excluding, certain domains.
Female rodents are less sensitive to ARs than males
Female humans are more sensitive ti ARs than males
Essentiality of the Key Events
Molecular Initiating Event Summary,
Key Event Summary
Provide an overall assessment of the essentiality for the key events in the AOP. Support calls for individual key events can be included in the molecular initiating event, key event, and adverse outcome tables above.
Weight of Evidence Summary
Summary Table
Provide an overall summary of the weight of evidence based on the evaluations of the individual linkages from the Key Event Relationship pages.
Quantitative Considerations
Summary Table
Provide an overall discussion of the quantitative information available for this AOP. Support calls for the individual relationships can be included in the Key Event Relationship table above.
Considerations for Potential Applications of the AOP (optional)
References