Ingestion of Superwarfarin Leading to Coagulopathy: A Case Report and Review of the Literature

Austin T. Nelson, BS; Joshua D. Hartzell, MD; Kenneth More, MD; Steven J. Durning, MD

Abstract

Superwarfarins are found in many pesticides, including D-con, Prufe I and II, Ramik, Talon-G, Ratak, and Contrac. Ingestion of can lead to significant morbidity and even mortality. Physicians need to consider this diagnosis in any patient presenting with coagulopathy of unclear etiology. We present a patient with superwarfarin-induced coagulopathy and review previous cases in adults in the literature. The patient is a 60-year-old man who presented to our medical center with painless hematuria. Laboratory studies revealed an elevated prothrombin time (PT) (42.5 seconds), partial thromboplastin time (PTT) (64.6 seconds), and international normalized ratio (INR) of 7. Liver-associated enzymes were normal, and complete blood cell count (CBC) showed no evidence of disseminated intravascular coagulation. Subsequent work-up included the absence of an inhibitor by mixing study and deficiencies of vitamin K-dependent coagulation factors. The patient's warfarin level was negative. A brodifacoum level was positive, confirming superwarfarin-induced coagulopathy. The patient is currently doing well with normal coagulation studies after receiving high doses of vitamin K for several weeks. The cause of his exposure to superwarfarin remains uncertain. Physicians need to be cognizant of this unusual cause of coagulopathy in adults. The appropriate diagnostic work-up and unique features of therapy are discussed.

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Cite this: Ingestion of Superwarfarin Leading to Coagulopathy: A Case Report and Review of the Literature - Medscape - Nov 28, 2006.

Table. Previous Reports of Unknown Ingestion of Superwarfarin Leading to Coagulopathy in Adults: Medline 1966-Present
Reference	Patient's Age and Sex	Possible Exposure	Studies	Presentation	Treatment	Outcome
Hui et al,^[8] 1996	76 yrs, man	Planted mosslike herbs around hut to brew tonic drinks; did not place rodenticide near herbs, but authors speculate that it was present	PT > 110.0 sec (11.0-15.0 sec) PTT > 110.0 sec (24.0-36.0 sec)	Hematemesis, abdominal pain	5u PRBC, 4u FFP vitamin K 100 mg IV once daily x 2 weeks, 50 mg x 1 week, oral 50 mg once daily	Died 6 months after initial presentation
Zupancic-Salek et al,^[9] 2005	20 yrs, man	Worked as agricultural technician where he was in contact with rodenticides	PT < 0.05 sec (0.70-1.30 sec) PTT 106.3 sec (24-33 sec)	Epistaxis, hematomas, hematuria, melena	rFIIa, 2u PRBC vitamin K 40 mg orally once daily x 3 months, 20 mg once-daily reduction, and 10 mg once daily x 1 month	Recovered without complications
Weitzel et al,^[10] 1990	48 yrs, man	Residence contained numerous packages of brodifacoum rodenticide	PT > 40 sec (10.8-13.2 sec) PTT > 100 (29.2-40.4 sec)	Epistaxis	FFP, vitamin K 100 mg orally once daily > 100 days	Recovered without complications
Weitzel et al,^[10] 1990	37 yrs, man	Unknown	PT > 60 sec (10.8-13.2 sec) PTT > 100 sec (29.2-40.4 sec)	Hematuria, hematomas, epistaxis	FFP, vitamin K 150-280 mg/day for > 150 days	Recovered without complications
Hollinger and Pastoor,^[11] 1993	38 yrs, man	Brodifacoum rodenticide at workplace	PT 143 sec (10.5-12.7 sec) PTT 90.1 sec (21.5-32.4 sec)	Bilateral flank pain, hematuria, ecchymosis	14u FFP, vitamin K 30-50 mg once-daily combination orally IM, IV; vitamin K 50 mg x 114 days	Recovered without complications
Pavlu et al,^[12] 2005	26 yrs, woman	Unknown	PT 150 sec (9.0-12.6 sec) PTT 92 sec (22-32 sec)	Nausea, vomiting, abdominal pain, hematuria, bleeding gums	Vitamin K 10 mg IV x 3 days, 100 mg orally x 7 days then reduced to 30 mg orally for 77 days	Recovered after initial treatment/lost to follow-up thereafter
Abell et al,^[13] 1994	39 yrs, woman	Spread rat poison around her house without gloves	PT 31.1 sec (11.7 sec) PTT 59.9 sec (27.6 sec)	Headache, nausea/vomiting, dyspnea, intracerebral hemorrhage	2u FFP and vitamin K -dosage and route not identified	Clot removed; recovered without complications thereafter
Poovalingam et al,^[14] 2002	38 yrs, man	Used Rattex for rats in shop that he owned	Unknown	Hematuria, abdominal pain, bleeding gums	FFP, high-dose vitamin K	Recovered without complications
Rauch et al,^[15] 1994	26 yrs, man	Unknown	PT 100 sec (11 sec) PTT 60 sec (27 sec)	Calf hematoma, hematemesis	FFP, vitamin K up to 200 mg IM then IV/24 hours, oral vitamin K 150 mg, and IM 100 mg	2-year treatment required; near-normal PT/PTT that periodically became elevated
Rauch et al,^[15] 1994	42 yrs, man	Unknown	PT > 50 sec (11 sec) PTT 84.4 (27 sec)	Hematuria, abdominal pain, epistaxis	Vitamin K 75 mg IV over 9-day period, then IV infusion of 4 mg/hr x 17 days; 30 mg orally x 3 months, then 200 mg orally for several months	Recovered without complications
Park et al,^[16] 1986	26 yrs, man	Worked in manufacturing plant for superwarfarins	PT 53 sec (12.5 sec) PTT 88 sec (25 sec)	Hematuria, bleeding gums, easy bruising	FFP, oral vitamin K x 7 months, then 10 mg IV on several occasions (study protocol)	Recovered without complications
Park et al,^[16] 1986	28 yrs, man	Worked in manufacturing plant for superwarfarins	PT 100 sec (12.5 sec) PTT 80 sec (25 sec)	Spontaneous hematomas, hematuria	FFP, vitamin K 10 mg IV on several occasions (study protocol)	Recovered without complications
Routh et al,^[17] 1991	29 yrs, man	Was taking warfarin (Coumadin) at time of presentation for subclavian vein thrombosis; no warfarin present in serum, positive brodifacoum	PT 95 sec (10.3-12.3 sec) PTT 66 sec (22.0-35.0 sec)	Abnormal clotting panel for warfarin follow-up - vaginal bleeding	Vitamin K 20 mg IV 3 times/week x 3 weeks	Died of septic shock with diffuse hemorrhagic diathesis
Huic et al,^[18] 2002	35 yrs, woman	Patient had rodenticide in her cellar	PT 0.11 sec (0.70-1.3 sec) PTT 67.9 sec	Hematochezia, weakness, loss of appetite, epistaxis, metrorrhagia	Red blood cells transfused, 3u FFP, cryoprecipitate, vitamin K 10-20 mg IV x 26 days, 10 mg orally x 2 weeks	Recovered without complications
Present report	60 yrs, man	Unknown - roach bait present in house	PT 42.5 sec (11.9-14.5 sec) PTT 64.6 sec (24.6-34.6 sec) INR 7.8	Hematuria	Vitamin K 10 mg IM during initial stay, 30 mg IM, 30 mg orally for 3 weeks	Recovered without complications

PT = prothrombin time; PTT = partial thromboplastin time; INR = international normalized ratio; IV = intravenous; IM = intramuscularly

Table. Previous Reports of Unknown Ingestion of Superwarfarin Leading to Coagulopathy in Adults: Medline 1966-Present
Reference	Patient's Age and Sex	Possible Exposure	Studies	Presentation	Treatment	Outcome
Hui et al,^[8] 1996	76 yrs, man	Planted mosslike herbs around hut to brew tonic drinks; did not place rodenticide near herbs, but authors speculate that it was present	PT > 110.0 sec (11.0-15.0 sec) PTT > 110.0 sec (24.0-36.0 sec)	Hematemesis, abdominal pain	5u PRBC, 4u FFP vitamin K 100 mg IV once daily x 2 weeks, 50 mg x 1 week, oral 50 mg once daily	Died 6 months after initial presentation
Zupancic-Salek et al,^[9] 2005	20 yrs, man	Worked as agricultural technician where he was in contact with rodenticides	PT < 0.05 sec (0.70-1.30 sec) PTT 106.3 sec (24-33 sec)	Epistaxis, hematomas, hematuria, melena	rFIIa, 2u PRBC vitamin K 40 mg orally once daily x 3 months, 20 mg once-daily reduction, and 10 mg once daily x 1 month	Recovered without complications
Weitzel et al,^[10] 1990	48 yrs, man	Residence contained numerous packages of brodifacoum rodenticide	PT > 40 sec (10.8-13.2 sec) PTT > 100 (29.2-40.4 sec)	Epistaxis	FFP, vitamin K 100 mg orally once daily > 100 days	Recovered without complications
Weitzel et al,^[10] 1990	37 yrs, man	Unknown	PT > 60 sec (10.8-13.2 sec) PTT > 100 sec (29.2-40.4 sec)	Hematuria, hematomas, epistaxis	FFP, vitamin K 150-280 mg/day for > 150 days	Recovered without complications
Hollinger and Pastoor,^[11] 1993	38 yrs, man	Brodifacoum rodenticide at workplace	PT 143 sec (10.5-12.7 sec) PTT 90.1 sec (21.5-32.4 sec)	Bilateral flank pain, hematuria, ecchymosis	14u FFP, vitamin K 30-50 mg once-daily combination orally IM, IV; vitamin K 50 mg x 114 days	Recovered without complications
Pavlu et al,^[12] 2005	26 yrs, woman	Unknown	PT 150 sec (9.0-12.6 sec) PTT 92 sec (22-32 sec)	Nausea, vomiting, abdominal pain, hematuria, bleeding gums	Vitamin K 10 mg IV x 3 days, 100 mg orally x 7 days then reduced to 30 mg orally for 77 days	Recovered after initial treatment/lost to follow-up thereafter
Abell et al,^[13] 1994	39 yrs, woman	Spread rat poison around her house without gloves	PT 31.1 sec (11.7 sec) PTT 59.9 sec (27.6 sec)	Headache, nausea/vomiting, dyspnea, intracerebral hemorrhage	2u FFP and vitamin K -dosage and route not identified	Clot removed; recovered without complications thereafter
Poovalingam et al,^[14] 2002	38 yrs, man	Used Rattex for rats in shop that he owned	Unknown	Hematuria, abdominal pain, bleeding gums	FFP, high-dose vitamin K	Recovered without complications
Rauch et al,^[15] 1994	26 yrs, man	Unknown	PT 100 sec (11 sec) PTT 60 sec (27 sec)	Calf hematoma, hematemesis	FFP, vitamin K up to 200 mg IM then IV/24 hours, oral vitamin K 150 mg, and IM 100 mg	2-year treatment required; near-normal PT/PTT that periodically became elevated
Rauch et al,^[15] 1994	42 yrs, man	Unknown	PT > 50 sec (11 sec) PTT 84.4 (27 sec)	Hematuria, abdominal pain, epistaxis	Vitamin K 75 mg IV over 9-day period, then IV infusion of 4 mg/hr x 17 days; 30 mg orally x 3 months, then 200 mg orally for several months	Recovered without complications
Park et al,^[16] 1986	26 yrs, man	Worked in manufacturing plant for superwarfarins	PT 53 sec (12.5 sec) PTT 88 sec (25 sec)	Hematuria, bleeding gums, easy bruising	FFP, oral vitamin K x 7 months, then 10 mg IV on several occasions (study protocol)	Recovered without complications
Park et al,^[16] 1986	28 yrs, man	Worked in manufacturing plant for superwarfarins	PT 100 sec (12.5 sec) PTT 80 sec (25 sec)	Spontaneous hematomas, hematuria	FFP, vitamin K 10 mg IV on several occasions (study protocol)	Recovered without complications
Routh et al,^[17] 1991	29 yrs, man	Was taking warfarin (Coumadin) at time of presentation for subclavian vein thrombosis; no warfarin present in serum, positive brodifacoum	PT 95 sec (10.3-12.3 sec) PTT 66 sec (22.0-35.0 sec)	Abnormal clotting panel for warfarin follow-up - vaginal bleeding	Vitamin K 20 mg IV 3 times/week x 3 weeks	Died of septic shock with diffuse hemorrhagic diathesis
Huic et al,^[18] 2002	35 yrs, woman	Patient had rodenticide in her cellar	PT 0.11 sec (0.70-1.3 sec) PTT 67.9 sec	Hematochezia, weakness, loss of appetite, epistaxis, metrorrhagia	Red blood cells transfused, 3u FFP, cryoprecipitate, vitamin K 10-20 mg IV x 26 days, 10 mg orally x 2 weeks	Recovered without complications
Present report	60 yrs, man	Unknown - roach bait present in house	PT 42.5 sec (11.9-14.5 sec) PTT 64.6 sec (24.6-34.6 sec) INR 7.8	Hematuria	Vitamin K 10 mg IM during initial stay, 30 mg IM, 30 mg orally for 3 weeks	Recovered without complications

PT = prothrombin time; PTT = partial thromboplastin time; INR = international normalized ratio; IV = intravenous; IM = intramuscularly

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Ingestion of Superwarfarin Leading to Coagulopathy: A Case Report and Review of the Literature

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