Brodifacoum intoxication with marijuana smoking

Archives of Pathology & Laboratory Medicine, Jan 1997 by Francisco G La Rosa, Susan H Clarke, Jerry B Lefkowitz

* 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. As a consequence, the patient developed a prolonged coagulopathy that persisted for more than 1 year. To our knowledge, this is the first case reported in the literature in which superwarfarin intoxication has been associated with marijuana smoking. This report should increase the awareness of pathologists and clinicians when examining a patient with a history of drug abuse who exhibits persistent vitamin K,dependent coagulopathy.

(Arch Pathol Lab Med. 1997;121:67-69)

The increased prevalence of rodents resistant to warfarin led to the development of the superwarfarins brodifacoum, bromadiolone, difenacoum, and chlorphacinone.1 These rodenticides have an approximate toxic potency in animals 100-fold greater on a molar basis than that of warfarin and a half-life as much as 60 times longer. In humans, a severe and prolonged coagulopathy can result from superwarfarin ingestion.2 A clear dose evaluation of their toxicity is not well defined in humans. A general assessment of the clinical cases reported in the literature suggests great individual variability with regard to toxicity and the amount of poison ingested. Superwarfarin intoxication is treated with large intravenous, intramuscular, and oral doses of vitamin K, (phytomenadione).3

In a recent review, Rauch et al4 found at least 18 reports of superwarfarin intoxication, 10 of which were associated with brodifacoum. Additionally, in 1992 there were more than 10 000 reported superwarfarin exposures; most were accidental, especially in children.5 We report here an unusual case of brodifacoum intoxication in a 17-year-old boy with a long history of severe alcohol and drug abuse, and a history of smoking marijuana mixed with the rodent poison d-CON, a trademark of brodifacoum.

REPORT OF A CASE

A 17-year-old boy presented with mucosal bleeding, skin bleeding, a prolonged prothrombin time (PT) and elevated PIVKA-II (factor II induced in vitamin K absence) antigen in March 1994. At this time the patient denied ingestion of warfarin or rodenticide. He was treated with two units of fresh frozen plasma and both intravenous and oral vitamin K,. During this treatment he received verapamil for hypertension. Vitamin K, treatments are outlined in Table 1.

Two months later, the patient was brought to the emergency room after suffering a syncopal episode. He presented with a complete heart block thought to be secondary to verapamil intoxication. The patient was intubated for airway protection and received repeated stomach lavages with charcoal. He was transferred to the intensive care unit for further evaluation. During the course of this hospitalization, members of his family found the following items in the patient's bedroom: marijuana, hallucinogenic mushrooms, bottles of alcoholic beverages, a large tube of glue, heparin vials, prescription drug bottles, hypodermic needles, and a box of d-CON Mouse-Prufe II rodent killer (Reckitt and Colman Inc, Montvale, NJ), which was 3/4 empty. On questioning, the patient admitted smoking marijuana mixed with rodenticide. He was transferred to a psychiatric unit following release from the intensive care unit. After discharge, his vitamin K, treatments, both parenteral infusion and oral, were continued for an additional 3 months (Table 1). Prothrombin time and activated partial thromboplastin times (APTT) were performed periodically. The patient was lost to follow-up after 3 months but reappeared 7 months after his first presentation. At that time his PT result was normal. Again, the patient was lost to follow-up.

Fourteen months after the original presentation, the patient was admitted to the hospital with complaints of bilateral flank pain with hematuria and bleeding from the nasal and oral mucosa. At this admission, the patient reported having been in an altercation. He also claimed that he had not smoked or otherwise ingested brodifacoum since the original episode 420 days earlier. Admission PT and APTT values were found to be extremely prolonged. The patient's coagulopathy was treated with transfusion of four units of fresh frozen plasma over 2 days and both oral and intravenous vitamin K, (Table 1).

After discharge when emotionally stable, the patient described the method he used to smoke marijuana mixed with brodifacoum. He had learned this from a group of friends at a party where marijuana mixed with d-CON was being used. During the entire course of this coagulopathy, the patient has consistently denied oral or parenteral use of the rat poison.

LABORATORY METHODS AND FINDINGS

The Figure illustrates the time course of PT and APTT measurements in this patient. All blood specimens for coagulation studies were drawn into 3.2% buffered sodium citrate. From days 1 through 250 all PT and APTT testing was performed at The Children's Hospital, Denver, Colo, using the ACL 300 analyzer and Instrumentation Laboratories reagents (Instrumentation Laboratories, Lexington, Mass). The reference ranges and coefficients of variation (CVs) for these assays are as follows: PT, 12.4-14.4 seconds, 0.88% CV; APTT, 22.9-32.5 seconds, 2.47% CV From days 420 through 466, all PT and APTT testing was performed at University Hospital, Denver, using the ACL 3000+ (Instrumentation Laboratories) and Organon Teknika reagents (Organon Teknika, Durham, NC). The reference ranges and CVs for these assays are as follows: PT, 11.2-14.3 seconds, 0.9% CV; APTT, 24.4-35.4 seconds, 1.25% CV