Disease relevance of Klerat

• The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied [1].
• On admission, the brodifacoum level was 731 micrograms/L and the patient suffered severe urinary tract hemorrhage, requiring transfusion of blood products [2].
• CONCLUSION: This case demonstrates that brodifacoum poisoning is not an absolute contraindication to organ donation from brain-dead patients who have sustained a fatal ingestion [3].
• CASE: A woman presented at 22 weeks' gestation in hemorrhagic diathesis, attributed to the ingestion of rat poison containing brodifacoum several days earlier [4].
• In this case of an intentional ingestion of brodifacoum, a longitudinal analysis of specific coagulation factor derangements was carried out in an attempt to guide a future treatment strategy for this type of toxicity [5].

Psychiatry related information on Klerat

• Brodifacoum intoxication with marijuana smoking [6].
• We report the case of a 17-year-old boy with a significant history of drug and alcohol abuse, which included smoking marijuana mixed with brodifacoum [6].
• After the first 10 days of the child's hospitalization, the mother was identified as the source of brodifacoum, exemplifying the behavior described as Munchausen syndrome by proxy [7].

High impact information on Klerat

• Persistently increased prothrombin times necessitated treatment with phytonadione up to 80 mg/d for 4 months, until the brodifacoum level reached 10 micrograms/L [2].
• Spontaneous hemorrhage associated with accidental brodifacoum poisoning in a child [8].
• The long-term effects of the rodenticide, brodifacoum, on blood coagulation and vitamin K metabolism in rats [9].
• 5. Brodifacoum rapidly accumulated in the liver until the saturation of the microsomal binding site [9].
• Brodifacoum was also identified in rat feces from the family home [10].

Chemical compound and disease context of Klerat

• Phenobarbital decreased the anticoagulant effect, whereas SKF525A increased it, suggesting that a substantial portion of brodifacoum-induced hypoprothrombinemia is mediated by brodifacoum itself rather than by metabolites [11].
• In contrast, brodifacoum markedly reduced thrombin-induced relaxation after ischemia (Emax of 3.3 +/- 3.3%; p less than 0.05) yet significantly preserved the relaxant response to thrombin after ischemia and reperfusion (Emax of 36.6 +/- 4.3%) [12].
• It was found that the toxicity to all species was highest with brodifacoum and lowest with warfarin, and that only 0.005% brodifacoum would give a complete mortality in most species after one day's feeding [13].
• The results of the WBA 8119 toxicity tests are considered in relation to previous findings on other anticoagulant rodenticides, particularly difenacoum [14].

Biological context of Klerat

• The pharmacokinetics and pharmacodynamics of the 4-hydroxycoumarin anticoagulants, brodifacoum, difenacoum, and warfarin have been studied in the rabbit [15].
• 1. The long-term (30 days) effects of a single dose of brodifacoum (0.2 mg kg-1, orally) on blood clotting activity and on liver parameters of the vitamin K cycle were investigated in rats [9].
• Long-acting anticoagulant overdose: brodifacoum kinetics and optimal vitamin K dosing [16].
• RESULTS: A 24 month-old child developed bruises and a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) after receiving multiple doses of brodifacoum, a superwarfarin rodenticide [7].
• Vertebrate pest control programmes in New Zealand using bait containing brodifacoum have resulted in the primary and secondary poisoning and sub-lethal contamination of non-target species [17].

Anatomical context of Klerat

• This case demonstrates that after stabilization with fresh frozen plasma, high-dose oral vitamin K(1) therapy ( congruent with 7 mg/kg per 24 hours divided every 6 hours) was effective in treating brodifacoum-induced coagulopathy [16].
• Addition of the vitamin K 2,3-epoxide reductase inhibitors warfarin (5 to 100 microM) and brodifacoum (1 to 5 microM) to normal rat hepatocyte cultures produced a slight increase in hydroxyvitamin K formation and a marked inhibition of vitamin K formation [18].
• The determination of the anticoagulant rodenticide brodifacoum in blood serum by liquid chromatography with fluorescence detection [19].
• This case is also unique because the dam was unaffected, suggesting that fetuses are more susceptible to brodifacoum toxicity than adult animals [20].
• Brodifacoum was assayed in serum, small intestine, and liver by an HPLC method [11].

Associations of Klerat with other chemical compounds

• A comparative study of the effects of warfarin and brodifacoum on the relationship between vitamin K1 metabolism and clotting factor activity in warfarin-susceptible and warfarin-resistant rats [21].
• The pharmacological response to vitamin K has been determined by measuring prothrombin complex activity (P.C.A.) in male New Zealand White rabbits anticoagulated (P.C.A. less than 20%) with the long acting 4-hydroxycoumarin brodifacoum, at a dose (10 mg/kg) which produces maximum antagonism of vitamin K1 [22].
• The rodenticides brodifacoum, difenacoum, coumatetralyl and warfarin are determined in animal relicta by high-performance exclusion chromatography on porous silica [23].
• Diagnosis of brodifacoum intoxication using HPLC was confirmed only months after prolonged treatment with high dose vitamin K1 [24].
• A method to determine residue concentrations of anti-coagulant rodenticides, brodifacoum (BF) and bromadiolone (BD) in liver was developed, using gas chromatography/mass spectrometry [25].

Analytical, diagnostic and therapeutic context of Klerat

• Successful donation and transplantation of multiple organs after fatal poisoning with brodifacoum, a long-acting anticoagulant rodenticide: case report [3].
• A rapid, sensitive and selective method for the simultaneous determination of bromadiolone, flocoumafen and brodifacoum in whole blood using warfarin as internal standard (IS) by high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC/ESI-MS) has been developed and validated [26].
• Quantification of brodifacoum in plasma and liver tissue by HPLC [27].
• Successful liver transplantation from a donor with brodifacoum intoxication [28].
• We describe our use of a liver allograft from a donor who died of intracranial hemorrhage after brodifacoum ingestion [28].

References