When the blood keeps on flowing

Last month, the police superintendent of New Orleans, Louisiana revealed an unusual problem to members of the New Orleans City Council’s Criminal Justice Committee. A pest infestation at police headquarters was contributing to ‘deplorable’ conditions, evidence control issues and beyond. ‘The rats eating our marijuana, they’re all high,’ the superintendent said. While this news elicited jokes and jibes, evidence destruction is no laughing matter. To protect these critical materials, evidence managers may turn to pest management professionals, who most often rely on anticoagulant rodenticides.^1–3

Warfarin, a first generation anticoagulant rodenticide, entered the market in 1948 as a pest control agent. Warfarin inhibits an enzyme called vitamin K epoxide reductase. This throws a spoke in the vitamin K cycle, thus limiting the production of various vitamin K-dependent clotting factors.^3–8 Without these clotting factors, lethal haemorrhage results. Humans are impacted by anticoagulants in the same manner as rodents. Despite its life-ending potential, warfarin was approved for human use in 1954 for its life-saving properties. Warfarin has proven critical in managing undesirable blood clotting seen in conditions like venous thromboembolism, heart attacks, and strokes.⁹

The widespread use of warfarin for rodent control reportedly led to rodent populations acquiring resistance.^10–11 A second generation of anticoagulant rodenticides that share structural similarities with warfarin were developed that are more potent, earning the nickname ‘superwarfarins’.¹² These have been viewed as supervillains, posing ‘unreasonable risks’ to a range of wildlife and human life, leading to access and use regulations.¹³ Superwarfarins were never intended for human use, but they have been used to menace people and are a potential public health problem.^14–17 

Part of the problem is diagnosis and treatment. While diagnosing impaired blood clotting (coagulopathy) is straightforward, pinpointing that it is due to superwarfarin poisoning is difficult.³ Vitamin K treatment is used to counter both warfarin and superwarfarin poisonings, but the poison’s biological half-life is critical to treatment management.^18–21 The half-life of warfarin is measured in hours to days, while it is measured in weeks to months for superwarfarins. Long-term vitamin K treatment is needed to restore and maintain healthy coagulation while a superwarfarin clears a patient’s system. 

Time was of the essence in spring 2018 when an outbreak of coagulopathy hit Illinois, with 155 cases identified between March and April.²² Four patients died. None of the patients took prescription anticoagulants, nor did any report exposure to anticoagulant rodenticides. Clinical signs and symptoms – including positive responses to high doses of vitamin K – alerted health professionals that a long-acting anticoagulant was behind the outbreak. 

A common culprit

Analysis of blood samples via high-performance liquid chromatography–mass spectrometry (HPLC–MS) revealed that brodifacoum was the culprit – one of the most encountered superwarfarins in clinical poisoning cases. A joint investigation by health and law enforcement agencies revealed that this mass poisoning was due to adulterated synthetic cannabinoids – a drug product patients had disclosed using shortly before hospitalisation. 

Beyond Illinois, over three dozen poisoned patients were identified in eight other states, resulting in a large-scale multi-state investigation. Published reports do not offer definitive explanations for why the synthetic cannabinoids were adulterated with brodifacoum.²² Possibilities discussed included accidental poisoning, dangerous attempts to boost synthetic cannabinoid drug action and ‘malicious contamination’. 

About two years after the Illinois outbreak, a healthcare team in Italy weighed the possibility that their patient’s coagulopathy was also due to brodifacoum-adulterated synthetic cannabinoids.²⁰ Vitamin K treatment was already in progress when HPLC and LC–MS screening of patient biological samples revealed brodifacoum. This patient – who recovered – did not disclose any recent synthetic cannabinoid use or anticoagulant rodenticide exposure. A criminal investigation later established the poisoning occurred in a restaurant where the patient routinely had lunch, but did not disclose to the healthcare team whether the poisoning was accidental or an attempt at homicide.

Latent evil

Murder was the case in a recently reported brodifacoum poisoning in China.⁴ The killer went with this poison because they knew of its latency period, which they counted on to evade suspicion. There can be a delay of three to nine days before brodifacoum derails coagulation, and it could be weeks to months before lethal haemorrhage. The victim died an estimated 60 days after being poisoned, during which time they had two hospital stays to treat bleeding incidents. Postmortem LC–MS/MS analysis of the victim’s biological samples from their second hospital stay revealed brodifacoum poisoning.

A police investigation revealed the killer to be the patient’s co-worker, who took issue with the victim not repaying a loan. Reportedly, the killer used three ampules of a commercially available brodifacoum solution to poison a bottle of coke subsequently consumed by the victim about 10 days before their first hospital stay. During each hospital stay, vitamin K treatment saw improvement to the patient’s condition but treatment ended with discharge and a tragic sequence of events continued to unfold. The killer may have thought the victim’s delayed death would put them in the clear, but the detection of brodifacoum likely pointed straight to them due to their ‘previous criminal activities of brodifacoum poisoning’. 

Whether the red flags are clinical symptoms or histories, each requires investigation to mitigate danger.