Page 633 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

598 SECTION | VIII Rodenticides

VetBooks.ir units/kg, recombinant activated factor VII 1.2-4.8 mg or was treated with vitamin K 1 (100 mg) for 3 months, with
a half-life of 15 days.
fresh frozen plasma 15 mL/kg if no concentrate is avail-
The two most commonly recommended routes of vita-
able, and phytomenadione 10 mg IV (100 μg/kg body wt.
in a child) is recommended to be given. If there is no min K 1 administration are oral and subcutaneous.
active bleeding and the INR is , or 5 4.0, no treatment is Intramuscular injections in a hypoprothrombinemic ani-
recommended; if INR is $ 4.0 phytomenadione 10 mg mal can produce hematoma, and intravenous administra-
should be administered intravenously (Watt et al., 2005). tion of vitamin K 1 has been associated with anaphylaxis;
Animals with severe clinical bleeding, or markedly therefore, these routes are discouraged in the therapeutic
reduced PCVs, should receive fresh plasma or blood regimen (Clark and Halliwell, 1963).
transfusions because of the 4 8 h often required to Vitamin K 1 therapy may be reduced in a step-wise
increase clotting factor activity following vitamin K 1 ther- manner as long as the PT remains normal (Robben et al.,
apy (Chalermchaikit et al., 1993; Terneu et al., 2003; 1998). The length of treatment is presently decided by
Soubiron et al., 2000; McCarthy et al., 1997). evaluation of OSPT values for 2 days after the cessation
of vitamin K 1 administration. If prolonged OPST is found,
treatment is commonly continued for another week, but if
Specific it remains normal for 5 6 days, the vitamin K 1 treatment
Vitamin K 1 therapy is recommended in humans is usually terminated (Murphy et al., 1989).
(Terneu et al., 2003; Soubiron et al., 2000; McCarthy
et al., 1997; Boettcher et al., 2011) and animals with DIAGNOSIS
elevated coagulation times after exposure to anticoagulant
rodenticides (Robben et al., 1998; Murphy et al., 1989; Diagnostic approach to the bleeding patient has been
Mount et al., 1982). Vitamin K 1 (phylloquinone) is described by Johnstone (1989). A diagnostic protocol
the most effective form for the treatment of anticoagu- should utilize more than one coagulation test, since it is
lant rodenticide intoxication because of its immediate necessary to differentiate rodenticide poisoning from
availability for the synthesis of new clotting factors other coagulopathies, such as disseminated intravascular
(Chalermchaikit et al., 1993). coagulopathy, congenital factor deficiencies, hyperviscos-
The pharmacological half-life of vitamin K 1 is ity syndromes, platelet deficiencies or functional defects,
1.7 1 0.1 h in rabbits dosed with brodifacoum (Park and von Willebrand’s disease, and canine ehrlichiosis.
Leck, 1982). Prothrombin activity reaches peak improve- Hypovitaminosis K-associated bleeding has been reported
ment 4 h after administration of vitamin K 1 to rabbits in cats with malabsorption syndrome (Edwards and
anticoagulated with brodifacoum or difenacoum (Park and Russell, 1987).
Leck, 1982).
The duration of vitamin K 1 treatment is prolonged Analytical Chemistry
(Butcher et al., 1992) for the longer-acting chemicals. It
may be required for up to 2 weeks in diphacinone- A number of analytical methods have been reported for
exposed dogs (Mount and Feldman, 1983). Daily doses of detecting anticoagulant rodenticides in various matrices.
vitamin K 1 in the range of 0.25 2.5 mg/kg for 1 week Warfarin-specific analytical methods were generally not
are recommended for exposure to short-acting rodenti- adequate for the subsequently developed rodenticides, so
cides, and 2.5 5.0 mg/kg for 3 4 weeks is recommended a number of other methods were developed. These meth-
for exposure to long-acting rodenticides (Mount et al., ods include thin layer chromatography (TLC), high pres-
1985). Prolonged anticoagulation in rat poisoning has sure liquid chromatography (HPLC), mass spectroscopy
been reported by Jones et al. (1984) and Lipton and Klass (MS), and antibody-mediated tests. Coumarin antico-
(1984). Treatment for 48 days has been reported in a agulant rodenticides were initially detected using TLC
human case of flocoumafen exposure in which a half-life (Lau-Cam and Chu-Fong, 1972; Mallet et al., 1973); then,
of 6.7 days was estimated (Boettcher et al., 2011). In an immunoassay was developed to detect diphacinone and
intentional poisoning cases in humans, vitamin K 1 treat- chlorophacinone (Mount et al., 1988). Enantiomers of
ment may be required for 2 (Dolin et al., 2006)or3 warfarin, coumachlor, and coumafuryl were separated
months (Wu et al., 2009), or. A brodifacoum case had a chromatographically (Armstrong et al., 1993) to assist
56 day half-life (Olmos and Lo ´pez, 2007). Another report identification.
is of two concurrent cases at a clinical toxicology service Extraction and cleanup procedures often vary on the
that required prolonged treatment with oral vitamin K to matrix. For example, a dispersive solid-phase extraction
achieve normalization of coagulation studies. Case 1 had (dSPE) technique for multiple anticoagulant rodenticides
a brodifacoum elimination half-life of 33 days, and was was recently reported for blood or tissue matrices.
treated with vitamin K (100 mg) for 6 months. Case 2 Methods for bait and technical material, environmental