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Evaluation of risk factors in patients with vitamin K-dependent coagulopathy presumed to be caused by exposure to brodifacoum

  • Lee, Hee-Jeong (Division of Hematology and Oncology, Department of Internal Medicine, Chosun University Hospital) ;
  • You, Mi-Ra (Division of Hematology and Oncology, Department of Internal Medicine, Chosun University Hospital) ;
  • Moon, Woo-Ram (Division of Hematology and Oncology, Department of Internal Medicine, Chosun University Hospital) ;
  • Sul, Hyoung (Division of Hematology and Oncology, Department of Internal Medicine, Chosun University Hospital) ;
  • Chung, Choon-Hae (Division of Hematology and Oncology, Department of Internal Medicine, Chosun University Hospital) ;
  • Park, Chi-Young (Division of Hematology and Oncology, Department of Internal Medicine, Chosun University Hospital) ;
  • Park, Sang-Gon (Division of Hematology and Oncology, Department of Internal Medicine, Chosun University Hospital)
  • Received : 2013.05.14
  • Accepted : 2013.10.04
  • Published : 2014.07.01

Abstract

Background/Aims: Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. Methods: Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. Results: Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT]> 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). Conclusions: Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.

Keywords

References

  1. Hong J, Yhim HY, Bang SM, et al. Korean patients with superwarfarin intoxication and their outcome. J Korean Med Sci 2010;25:1754-1758. https://doi.org/10.3346/jkms.2010.25.12.1754
  2. Rauch AE, Weininger R, Pasquale D, et al. Superwarfarin poisoning: a significant public health problem. J Community Health 1994;19:55-65. https://doi.org/10.1007/BF02260521
  3. Abell TL, Merigian KS, Lee JM, Holbert JM, McCall JW 3rd. Cutaneous exposure to warfarin-like anticoagulant causing an intracerebral hemorrhage: a case report. J Toxicol Clin Toxicol 1994;32:69-73. https://doi.org/10.3109/15563659409000432
  4. Kim HY, Jeon HJ, Ko BS, Lee KH, Kim ST. Two cases of brodifacoum poisoning from inhalation route. Korean J Hematol 1996;31:473-479.
  5. Hadler MR, Shadbolt RS. Novel 4-hydroxycoumarin anticoagulants active against resistant rats. Nature 1975;253:275-277. https://doi.org/10.1038/253275a0
  6. Chua JD, Friedenberg WR. Superwarfarin poisoning. Arch Intern Med 1998;158:1929-1932. https://doi.org/10.1001/archinte.158.17.1929
  7. Pavlu J, Harrington DJ, Voong K, Savidge GF, Jan-Mohamed R, Kaczmarski R. Superwarfarin poisoning. Lancet 2005;365:628. https://doi.org/10.1016/S0140-6736(05)17916-1
  8. Lipton RA, Klass EM. Human ingestion of a 'superwarfarin' rodenticide resulting in a prolonged anticoagulant effect. JAMA 1984;252:3004-3005. https://doi.org/10.1001/jama.1984.03350210052030
  9. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giff in SL. 2009 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 27th Annual Report. Clin Toxicol (Phila) 2010;48:979-1178. https://doi.org/10.3109/15563650.2010.543906
  10. Park BK, Leck JB. A comparison of vitamin K antagonism by warfarin, difenacoum and brodifacoum in the rabbit. Biochem Pharmacol 1982;31:3635-3639. https://doi.org/10.1016/0006-2952(82)90587-1
  11. Bachmann KA, Sullivan TJ. Dispositional and pharmacodynamic characteristics of brodifacoum in warfarin- sensitive rats. Pharmacology 1983;27:281-288. https://doi.org/10.1159/000137881
  12. Bruno GR, Howland MA, McMeeking A, Hoffman RS. Long-acting anticoagulant overdose: brodifacoum kinetics and optimal vitamin K dosing. Ann Emerg Med 2000;36:262-267. https://doi.org/10.1067/mem.2000.108317
  13. Hui CH, Lie A, Lam CK, Bourke C. 'Superwarfarin' poi-soning leading to prolonged coagulopathy. Forensic Sci Int 1996;78:13-18. https://doi.org/10.1016/0379-0738(95)01835-2
  14. Wu YF, Chang CS, Chung CY, Lin HY, Wang CC, Shen MC. Superwarfarin intoxication: hematuria is a major clinical manifestation. Int J Hematol 2009;90:170-173. https://doi.org/10.1007/s12185-009-0374-6
  15. Jin MC, OuYang XK, Chen XH. High-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry for the determination of flocoumafen and brodifacoum in whole blood. J Appl Toxicol 2007;27:18-24. https://doi.org/10.1002/jat.1179
  16. Olmos V, Lenzken SC, del Carmen Paz M, et al. Quantification of brodifacoum, bromadiolone and difenacoum in human serum by HPLC with ultraviolet and fluorometric detection. Acta Toxicol Argent 2004;12:9-14.
  17. Watt BE, Proudfoot AT, Bradberry SM, Vale JA. Anticoagulant rodenticides. Toxicol Rev 2005;24:259-269. https://doi.org/10.2165/00139709-200524040-00005
  18. Eason CT, Murphy EC, Wright GR, Spurr EB. Assessment of risks of brodifacoum to non-target birds and mammals in New Zealand. Ecotoxicology 2002;11:35-48. https://doi.org/10.1023/A:1013793029831
  19. Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J 2007;7:99-111. https://doi.org/10.1038/sj.tpj.6500417
  20. Makris M, Watson HG. The management of coumarin- induced over-anticoagulation Annotation. Br J Haematol 2001;114:271-280. https://doi.org/10.1046/j.1365-2141.2001.02908.x
  21. O'Bryan SM, Constable DJ. Quantif ication of brodifacoum in plasma and liver tissue by HPLC. J Anal Toxicol 1991;15:144-147. https://doi.org/10.1093/jat/15.3.144
  22. Kaminsky LS, Zhang ZY. Human P450 metabolism of warfarin. Pharmacol Ther 1997;73:67-74. https://doi.org/10.1016/S0163-7258(96)00140-4
  23. Lieber CS. Alcohol and the liver: 1994 update. Gastroenterology 1994;106:1085-1105. https://doi.org/10.1016/0016-5085(94)90772-2
  24. Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health 1999;23:40-54.
  25. Schalekamp T, Klungel OH, Souverein PC, de Boer A. Increased bleeding risk with concurrent use of selective serotonin reuptake inhibitors and coumarins. Arch Intern Med 2008;168:180-185. https://doi.org/10.1001/archinternmed.2007.32
  26. Dalton SO, Sorensen HT, Johansen C. SSRIs and upper gastrointestinal bleeding: what is known and how should it inf luence prescribing? CNS Drugs 2006;20:143-151. https://doi.org/10.2165/00023210-200620020-00005
  27. Greenblatt DJ, von Moltke LL, Harmatz JS, Shader RI. Drug interactions with newer antidepressants: role of human cytochromes P450. J Clin Psychiatry 1998;59 Suppl 15:19-27.
  28. Choi KH, Kim AJ, Son IJ, et al. Risk factors of drug interaction between warfarin and nonsteroidal anti-inflammatory drugs in practical setting. J Korean Med Sci 2010;25:337-341.
  29. O'Reilly RA. Comparative interaction of cimetidine and ranitidine with racemic warfarin in man. Arch Intern Med 1984;144:989-991. https://doi.org/10.1001/archinte.1984.00350170143024
  30. Hungin AP, Rubin GP, O'Flanagan H. Co-prescription of H2 receptor blockers and proton pump inhibitors with warfarin in general practice. Postgrad Med J 1999;75:721-722. https://doi.org/10.1136/pgmj.75.890.721
  31. Rost S, Fregin A, Ivaskevicius V, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 2004;427:537-541. https://doi.org/10.1038/nature02214
  32. D'Andrea G, D'Ambrosio RL, Di Perna P, et al. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood 2005;105:645-649. https://doi.org/10.1182/blood-2004-06-2111
  33. Rettie AE, Korzekwa KR, Kunze KL, et al. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin- drug interactions. Chem Res Toxicol 1992;5:54-59. https://doi.org/10.1021/tx00025a009
  34. Higashi MK, Veenstra DL, Kondo LM, et al. Association between CYP2C9 genetic variants and anticoagulation- related outcomes during warfarin therapy. JAMA 2002;287:1690-1698. https://doi.org/10.1001/jama.287.13.1690
  35. Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW. Identification of the gene for vitamin K epoxide reductase. Nature 2004;427:541-544. https://doi.org/10.1038/nature02254
  36. Gage BF, Eby C, Johnson JA, et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 2008;84:326-331. https://doi.org/10.1038/clpt.2008.10
  37. Gage BF, Lesko LJ. Pharmacogenetics of warfarin: regulatory, scientific, and clinical issues. J Thromb Thrombolysis 2008;25:45-51. https://doi.org/10.1007/s11239-007-0104-y
  38. Visser LE, van Vliet M, van Schaik RH, et al. The risk of overanticoagulation in patients with cytochrome P450 CYP2C9*2 or CYP2C9*3 alleles on acenocoumarol or phenprocoumon. Pharmacogenetics 2004;14:27-33. https://doi.org/10.1097/00008571-200401000-00003
  39. Steward DJ, Haining RL, Henne KR, et al. Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics 1997;7:361-367. https://doi.org/10.1097/00008571-199710000-00004
  40. Aithal GP, Day CP, Kesteven PJ, Daly AK. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999;353:717-719. https://doi.org/10.1016/S0140-6736(98)04474-2
  41. Schalekamp T, Brasse BP, Roijers JF, et al. VKORC1 and CYP2C9 genotypes and phenprocoumon anticoagulation status: interaction between both genotypes affects dose requirement. Clin Pharmacol Ther 2007;81:185-193. https://doi.org/10.1038/sj.clpt.6100036
  42. Spahr JE, Maul JS, Rodgers GM. Superwarfarin poisoning: a report of two cases and review of the literature. Am J Hematol 2007;82:656-660. https://doi.org/10.1002/ajh.20784
  43. Zupancic-Salek S, Kovacevic-Metelko J, Radman I. Successful reversal of anticoagulant effect of superwarfarin poisoning with recombinant activated factor VII. Blood Coagul Fibrinolysis 2005;16:239-244. https://doi.org/10.1097/01.mbc.0000169215.70184.56

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