{"id":187,"title":"Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage","short_name":"VKOR inhibition resulting in coagulopathy","created_at":"2016-11-29T18:41:17.000-05:00","updated_at":"2023-09-25T16:26:54.000-04:00","corresponding_author":{"id":17712,"created_at":"2023-09-11T18:10:58.000-04:00","updated_at":"2023-09-11T18:10:58.000-04:00","subscribed":true,"novice":null},"aop_stressors":[{"stressor_id":195,"stressor_name":"Warfarin"},{"stressor_id":196,"stressor_name":"coumachlor"},{"stressor_id":197,"stressor_name":"coumatetralyl"},{"stressor_id":198,"stressor_name":"chlorophacinone"},{"stressor_id":199,"stressor_name":"diphacinone"},{"stressor_id":200,"stressor_name":"pindone"},{"stressor_id":201,"stressor_name":"3-[3-(4'-bromo[1,1'-biphenyl]-4-yl)-3-hydroxy-1-phenylpropyl]-4-hydroxy-2-benzopyrone"}],"aop_mies":[{"event_id":1134,"event":"Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone","event_type":"MolecularInitiatingEvent"},{"event_id":1138,"event":"Uncoupling of oxidative phosphorylation, Reduced ability to generate ATP","event_type":"MolecularInitiatingEvent"},{"event_id":1169,"event":"Anticoagulant rodenticide interferes with carboxylation of Gla proteins in bone, Impairment of post-translational modification (carboxylation) of osteocalcin","event_type":"MolecularInitiatingEvent"}],"aop_kes":[{"event_id":1122,"event":"Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failure of secondary hemostasis  ","event_type":"KeyEvent"},{"event_id":1130,"event":"Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage)","event_type":"KeyEvent"},{"event_id":1131,"event":"Failure in gamma-glutamyl carboxylation of  clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) ","event_type":"KeyEvent"},{"event_id":1132,"event":"Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal","event_type":"KeyEvent"},{"event_id":1133,"event":"Hemostasis, Depletion from blood of fully functional carboxylated clotting factors","event_type":"KeyEvent"},{"event_id":1135,"event":"Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction","event_type":"KeyEvent"},{"event_id":1151,"event":"Osteoporosis and vascular calcification, Bone deterioration","event_type":"KeyEvent"}],"aop_aos":[{"event_id":1136,"event":"Impaired recruitment , Population trajectory","event_type":"AdverseOutcome"}],"relationships":[{"relation":865,"upstream_event_id":1131,"upstream_event":"Failure in gamma-glutamyl carboxylation of  clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) ","downstream_event_id":1133,"downstream_event":"Hemostasis, Depletion from blood of fully functional carboxylated clotting factors"},{"relation":866,"upstream_event_id":1133,"upstream_event":"Hemostasis, Depletion from blood of fully functional carboxylated clotting factors","downstream_event_id":1122,"downstream_event":"Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failure of secondary hemostasis  "},{"relation":867,"upstream_event_id":1134,"upstream_event":"Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone","downstream_event_id":1131,"downstream_event":"Failure in gamma-glutamyl carboxylation of  clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) "},{"relation":868,"upstream_event_id":1122,"upstream_event":"Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failure of secondary hemostasis  ","downstream_event_id":1130,"downstream_event":"Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage)"},{"relation":869,"upstream_event_id":1130,"upstream_event":"Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage)","downstream_event_id":1132,"downstream_event":"Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal"},{"relation":870,"upstream_event_id":1132,"upstream_event":"Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal","downstream_event_id":1135,"downstream_event":"Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction"},{"relation":871,"upstream_event_id":1135,"upstream_event":"Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction","downstream_event_id":1136,"downstream_event":"Impaired recruitment , Population trajectory"}]}