J Korean Med Sci.  2010 Dec;25(12):1754-1758. 10.3346/jkms.2010.25.12.1754.

Korean Patients with Superwarfarin Intoxication and Their Outcome

• Hong J
• Yhim HY
• Bang SM
• Bae SH
• Yuh YJ
• Yoon SS
• Yoon HJ
• Kim ST
• Chi HS

• KMID: 1792899
• DOI: http://doi.org/10.3346/jkms.2010.25.12.1754

Abstract

This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.

Keyword

Superwarfarin; Brodifacoum; Vitamin K; Rodenticides

MeSH Terms

4-Hydroxycoumarins/*poisoning
Adult
Aged
Aged, 80 and over
Anticoagulants/*poisoning
Antifibrinolytic Agents/therapeutic use
Environmental Exposure
Female
Hemorrhage/*chemically induced/diagnosis/drug therapy
Humans
Male
Middle Aged
Partial Thromboplastin Time
Prothrombin Time
Republic of Korea
Treatment Outcome
Vitamin K 1/therapeutic use

Reference

1. Chua JD, Friedenberg WR. Superwarfarin poisoning. Arch Intern Med. 1998. 158:1929–1932.

2. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report. Clin Toxicol (Phila). 2009. 47:911–1084.

3. 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.

4. Lee JH, Kim H, Han HS, Lee K, Kim S. A case of superwarfarin intoxication without a definitive history of brodifacoum exposure. Korean J Hematol. 2009. 44:53–57.

5. Kim SY, Cho SY, Lee HJ, Suh JT, Oh SH, Lee WI, Park TS, Yoon HJ. Superwarfarin intoxication of unknown etiology accompanying hemoperitoneum in a patient on fluconazole therapy. Ann Clin Lab Sci. 2010. 40:300–303.

6. Laurence D. Clinical pharmacholgy. 1973. Edinburgh, London and New York: Churchill Livingstone;234–235.

7. Park BK, Leck JB. A comparison of vitamin K antagonism by warfarin, difenacoum and brodifacoum in the rabbit. Biochem Pharmacol. 1982. 31:3635–3639.

8. Lund M. Comparative effect of the three rodenticides warfarin, difenacoum and brodifacoum on eight rodent species in short feeding periods. J Hyg (Lond). 1981. 87:101–107.

9. Weitzel JN, Sadowski JA, Furie BC, Moroose R, Kim H, Mount ME, Murphy MJ, Furie B. Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases. Blood. 1990. 76:2555–2559.

10. Chow EY, Haley LP, Vickars LM, Murphy MJ. A case of bromadiolone (superwarfarin) ingestion. CMAJ. 1992. 147:60–62.

11. Hui CH, Lie A, Lam CK, Bourke C. 'Superwarfarin' poisoning leading to prolonged coagulopathy. Forensic Sci Int. 1996. 78:13–18.

12. Katona B, Wason S. Superwarfarin poisoning. J Emerg Med. 1989. 7:627–631.

13. Park BK, Scott AK, Wilson AC, Haynes BP, Breckenridge AM. Plasma disposition of vitamin K1 in relation to anticoagulant poisoning. Br J Clin Pharmacol. 1984. 18:655–662.

14. Pavlu J, Harrington DJ, Voong K, Savidge GF, Jan-Mohamed R, Kaczmarski R. Superwarfarin poisoning. Lancet. 2005. 365:628.

15. 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.

16. 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.

17. Zupancić-Salek S, Kovacević-Metelko J, Radman I. Successful reversal of anticoagulant effect of superwarfarin poisoning with recombinant activated factor VII. Blood Coagul Fibrinolysis. 2005. 16:239–244.

18. 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.

19. 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.