Synthetic cannabinoids, also known as K2 and spice, are heterogeneous psychoactive
compounds identified as substances of abuse (
1
,
2
). On March 22, 2018, the Illinois Department of Public Health was notified by the
Illinois Poison Center of four patients seen in emergency departments (EDs) during
the preceding 2 weeks with unexplained bleeding and high international normalized
ratios (INRs; range from 5 to >20 [normal <1.1]), indicating a clotting disorder,
and reported synthetic cannabinoid use during the previous 3 days. None reported taking
prescription anticoagulants or exposure to anticoagulant rodenticides. An investigation
by the Illinois Department of Public Health, the Illinois Poison Center, CDC, local
health departments, and law enforcement agencies was initiated to identify additional
cases, ascertain epidemiologic links among patients, and implement control measures.
Requests for information regarding patients with serious bleeding and an elevated
INR without a definitive etiology identified on or after February 1, 2018, were issued
to Illinois EDs, emergency medical services, health care providers, local health departments,
and coroners through Epi-X,* state and local health alert systems, and electronic
distribution lists. Syndromic surveillance queries were developed by the Illinois
Department of Public Health and implemented to identify patients evaluated at EDs
and urgent care centers. Seven press releases encouraged anyone with a serious reaction
after using synthetic cannabinoids to seek immediate medical attention.
Based on clinical signs and symptoms (unexplained bleeding, prolonged high INR values,
and response to fresh frozen plasma and high doses of vitamin K), exposure to a long-acting
vitamin K antagonist was suspected. Case definitions were developed based on signs
and symptoms, synthetic cannabinoid exposure, and laboratory findings (Box). Data
concerning signs and symptoms; synthetic cannabinoid use, brand, and location of purchase;
and exposure to rodenticides, prescription anticoagulants, and illicit drugs were
collected through patient interviews, medical chart abstraction, and Illinois Poison
Center consultations. Blood samples were tested for presence of anticoagulants by
high-performance liquid chromatography–tandem mass spectrometry (NMS Laboratories,
Willow Grove, Pennsylvania).
BOX
Case definitions for unexplained bleeding after use of synthetic cannabinoids — Illinois,
2018
Clinical criteria
Bruising, nosebleeds, bleeding gums, bleeding disproportionate to injury, vomiting
blood, coughing up blood, blood in urine or stool, or excessively heavy menstrual
bleeding.
Laboratory criteria
Elevated international normalized ratios (INRs; ≥2.0) or abnormal coagulation profile
(e.g., prothrombin time in absence of INR values) for which there is no other clinical
explanation, or
Detection of a long-acting anticoagulant (e.g., brodifacoum) in blood, serum, plasma,
or urine, as determined by reference laboratory testing.
Case classification
Suspected case
One or more of the clinical criteria listed above in a patient, without an alternative
explanation, and with reported use of synthetic cannabinoids or unknown drugs, or
with some suspicion of previous or current drug use or exposure.
Probable case
One or more of the clinical criteria listed above in a patient with reported use of
synthetic cannabinoids in the 3 months preceding illness onset (by patient, proxy,
medical record, or health care provider), and laboratory evidence of coagulopathy
as measured by meeting the first laboratory criterion listed above, or
One or more of the clinical criteria listed above, and meeting both laboratory criteria
listed above, with no other explanation of results.
Confirmed case
One or more of the clinical criteria listed above in a patient, with reported use
of synthetic cannabinoids in the 3 months preceding illness onset (by patient, proxy,
medical record, or health care provider), and meeting the second laboratory criterion
listed above.
As of April 25, 2018, a total of 155 cases (76 confirmed and 79 probable) had been
identified; four (2.6%) patients died from major bleeding events. Median patient age
was 32 years (range = 18–65 years), 115 (74%) were male, 81 (52%) were non-Hispanic
white, 147 (95%) were hospitalized, and eight (5%) were treated in an ED only. The
most frequently reported sign was hematuria (125; 81%); all patients reported bleeding
from at least one site. INRs were elevated in all patients. All 81 (52%) analyzed
clinical specimens from patients with a confirmed or probable case were positive for
brodifacoum, a long-acting vitamin K antagonist used in rodenticides. Although cases
clustered in two geographic areas (the Chicago area and seven neighboring counties
in central Illinois), no single product source has been identified. Law enforcement
is investigating the synthetic cannabinoid distribution network. Thirty-eight patients
have been identified in eight other states, and CDC is conducting a multistate investigation
(
3
). Product testing is ongoing in Illinois; some products in other states have tested
positive for brodifacoum (
4
). Currently, the reason why brodifacoum was present in the synthetic cannabinoids
is not known.
In 2017, 26 synthetic cannabinoids were listed as Schedule I substances under the
Controlled Substances Act (
5
). However, they are often marketed as alternatives to marijuana or labeled as not
for human consumption (
5
,
6
). They remain available for purchase, are relatively inexpensive, and are sometimes
favored over marijuana because they are not detected in routine drug testing (
2
,
6
). The synthetic cannabinoid supply chain is unregulated, resulting in variable product
compositions (
2
). Given the various compounds and unclear provenance, use of these products can result
in unpredictable health effects (
1
). Stronger public messaging is needed and should target persons at risk. Engaging
substance abuse services and community coalitions might improve outreach. Health care
providers should consider vitamin K-dependent coagulopathy in patients with unexplained
bleeding and reported or suspected synthetic cannabinoid use.