Rat Poison in Synthetic Cannabinoids: The 2018 Illinois Bleeding Outbreak

Synthetic cannabinoids — sold as "K2" or "spice" — are a varied group of psychoactive compounds identified as substances of abuse. In the spring of 2018, some of them in Illinois turned out to contain something far more dangerous: brodifacoum, a long-acting vitamin K antagonist used in rodenticides, which stops blood from clotting.

How it was found

On March 22, 2018, the Illinois Poison Center alerted the Illinois Department of Public Health to four patients seen in emergency departments over the previous 2 weeks. All had unexplained bleeding and very high international normalized ratios (INRs) — from 5 to more than 20, where normal is under 1.1 — signaling a clotting disorder. All had used synthetic cannabinoids in the previous 3 days, and none took prescription blood thinners or had been exposed to rat poison.

The state health department, the poison center, CDC, local health departments and law enforcement launched an investigation. They asked emergency departments, emergency medical services, providers, local health departments and coroners to report anyone with serious bleeding and a high INR without a clear cause since February 1, 2018; built syndromic surveillance searches of emergency and urgent care visits; and issued seven press releases urging anyone with a serious reaction after using synthetic cannabinoids to get medical care at once.

The pattern — unexplained bleeding, INRs that stayed high, and a response to fresh frozen plasma and high doses of vitamin K — pointed to a long-acting vitamin K antagonist.

The outbreak

As of April 25, 2018:

Every patient bled from at least one site, and every patient had an elevated INR. Cases clustered in the Chicago area and seven neighboring counties in central Illinois, but no single product source was found; law enforcement was investigating the distribution network. Another 38 patients had been identified in eight other states, and CDC opened a multistate investigation. Some products in other states tested positive for brodifacoum. Why it was in the synthetic cannabinoids was not known.

Who counted as a case

Clinical signs included bruising, nosebleeds, bleeding gums, bleeding out of proportion to an injury, vomiting or coughing up blood, blood in urine or stool, and very heavy menstrual bleeding.

• Confirmed: a clinical sign, synthetic cannabinoid use in the 3 months before illness, and a long-acting anticoagulant such as brodifacoum detected by a reference laboratory.
• Probable: a clinical sign with synthetic cannabinoid use and an INR of 2.0 or higher (or another abnormal clotting test) with no other explanation — or a clinical sign meeting both laboratory criteria.
• Suspected: an unexplained clinical sign with reported or suspected use of synthetic cannabinoids or unknown drugs.

Why synthetic cannabinoids are risky

In 2017, 26 synthetic cannabinoids were listed as Schedule I substances under the Controlled Substances Act. Still, they are often marketed as alternatives to marijuana or labeled "not for human consumption." They remain easy and cheap to buy, and some users prefer them because routine drug tests don't detect them. The supply chain is unregulated, so what's in a product varies — and with so many compounds of unclear origin, the health effects are unpredictable.

The authors call for stronger public messaging aimed at people at risk, with substance abuse services and community coalitions helping to reach them. Healthcare providers should consider vitamin K–dependent clotting disorders in any patient with unexplained bleeding who uses, or may use, synthetic cannabinoids.

Sources

Based on Moritz E, Austin C, Wahl M, et al., "Notes from the Field: Outbreak of Severe Illness Linked to the Vitamin K Antagonist Brodifacoum and Use of Synthetic Cannabinoids — Illinois, March–April 2018," Morbidity and Mortality Weekly Report 67(21), Centers for Disease Control and Prevention; a work of the United States government in the public domain. Original report.