According to the AAPCC,
3 exposures to superwarfarins in 2004 numbered 16,054, with 14,229 of these poisonings occurring in patients younger than 6 years. All of the superwarfarins work by inhibiting the generation of the activated form of vitamin K
1 via inhibition of vitamin K
1 reductases.
4 Activation of the coagulation factors II, VII, IX, and X require the presence of vitamin K as a cofactor. When vitamin K cannot be regenerated, the coagulation factors cannot be activated, and a coagulopathy results involving both the extrinsic and intrinsic coagulation pathways.
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Superwarfarins have a half-life of approximately 6 to 8 weeks.
6 Of the vitamin K–dependent factors, factor VII has the shortest half-life, at 5 hours.
6 Therefore, factor VII levels are used to monitor synthesis of vitamin K–dependent coagulation factors.
7 Patients are able to tolerate a reduction in coagulation factor synthesis of as much as 70% before manifesting coagulation disorders.
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Chronic exposures and overdoses of superwarfarins may result in bleeding from any organ system. However, more than one system is usually involved. Other possible results of chronic exposure include ecchymoses, epistaxis, friable gums, hematemesis, hematuria, hemoptysis, melena, petechiae, and vaginal bleeding.
8 Measurements of specific coagulation factors support the diagnosis of superwarfarin toxicity if all vitamin K–dependent factors (II, VII, IX, and X) are decreased while others remain normal in the absence of Coumadin therapy, liver disease, or the use of an inhibitor.
4 In addition to using HPLC and RIA/ELISA to make diagnoses of toxicity, the vitamin K
1(2,3-epoxide):K
1 ratio can be used, with a ratio of 2:3 (normal, 0.1:0.2) indicating ingestion of superwarfarins.
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There is no specific therapeutic regimen for patients diagnosed with superwarfarin poisoning other than restoration of normal PT and coagulation factor levels. In patients with active bleeding, treatment involves administering fresh frozen plasma and/or coagulation factor concentrates, in addition to packed red blood cells and oral vitamin K.
5 In patients who no longer demonstrate active bleeding or life-threatening hemorrhage but continue to have prolongation of PT, supratherapeutic doses of oral vitamin K (>100 mg daily) have been demonstrated to normalize PT.
5 Monitoring of broudifacoum concentrations are useful for predicting when to terminate therapy.
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