A 24-year-old man presented with uncontrollable epistaxis. He said he had been bleeding "a ton" from his nose continuously for four hours. He denied recent trauma, and explained that this epistaxis was sudden onset. He had no past medical history, and denied previous episodes of excessive bleeding. An examination demonstrated no signs of trauma and was unremarkable aside from the epistaxis. His nostrils revealed no obvious bleeding vessels for cauterization. His social history was remarkable for occasional drinking, marijuana use, and recent use of synthetic marijuana.
His vital signs were a heart rate of 85 bpm, blood pressure of 135/80 mmHg, temperature of 98°F, and pulse oximetry of 100% on room air. Blood work revealed a hemoglobin of 13, hematocrit of 39, platelet of 250, PT of 35, INR of 8, and a PTT of 140.
Reports have recently been recounted of synthetic cannabinoids adulterated with brodifacoum, a long-acting vitamin K antagonist normally used in rat poison. More than 160 people presented to a U.S. health care facility between March and April 2018 with unexplained bleeding. Four fatalities were reported, all in Illinois. Lab testing confirmed the presence of brodifacoum in 18 people. Users described bleeding from their eyes and ears as well as heavy menstrual periods, frequent and severe nose bleeds, and gum bleeding.
This outbreak appears to be from an unintentional adulteration of synthetic marijuana, but some reports have users intentionally smoking marijuana with brodifacoum for a greater high and to potentiate the effects of the illicit drug. The first report in the literature was a 17-year-old boy who presented to the ED with mucosal and skin bleeding, and was found to have a prolonged PT. (Arch Pathol Lab Med 1997;121[1]:67.) Another case reported a 37-year-old-man who smoked crack cocaine mixed with brodifacoum and presented with a severe coagulopathy. (N Engl J Med 2001;345[9]:700.)
Brodifacoum is a vitamin K antagonist similar to Coumadin but much longer acting. It is categorized as a superwarfarin, first introduced in 1975 for warfarin-resistant rodents.
Coumadin Brodifacoum
Half-life 20-60 hrs 20-130 days
LD50 3 mg/kg 0.27 mg/kg
Brodifacoum causes anticoagulation by inhibiting the action of vitamin K 2,3-epoxide reductase in the vitamin K cycle. The deficiency in active vitamin K leads to functionally inactive vitamin K-dependent coagulation factors II, VII, IX, IX, X, and proteins C and S. Acute symptoms are all associated with bleeding, and include hemoptysis, hematuria, GI bleeding, retroperitoneal hemorrhage, intracranial hemorrhage, and epistaxis.
Treating brodifacoum toxicity is similar to Coumadin reversal; vitamin K and PCC administration are the mainstays of treatment. Brodifacoum is more complicated because of the prolonged half-life and prolonged period of anticoagulation. Brodifacoum poisoning patients must first be divided into two groups to decide which treatment to give.
Unintentional Ingestions
These are generally children who present to the ED after accidentally eating a pellet of rat poisoning. These patients are generally just curious and exploring their environment; they tend to put a pellet in their mouth. They should be examined for active bleeding, and can be discharged home if there is none. Performing coagulation studies is unnecessary because the effects on the PT/INR from superwarfarins are delayed. These children should follow up with their doctors, but do not need laboratory testing unless they develop bleeding. Those patients who have active bleeding on presentation should have lab studies consisting of CBC, BMP, PT/INR, PTT, and type and screen.
Anticoagulation is reversed using PCC or oral vitamin K. Patients can be discharged if bleeding is controlled, but they need close follow-up for INR checks and repeat dosing of vitamin K until PT/INR levels normalize for several days without treatment.
Intentional Ingestions
These patients should be admitted and serial PT/INRs obtained because brodifacoum can cause delayed coagulopathy. PCC along with IV vitamin K should be administered for life-threatening bleeding. These patients should be given oral vitamin K starting at 50 mg three to four times a day for the first two days after bleeding is controlled. Oral vitamin K is continued for weeks, even months, until the INR normalizes even when bleeding has resolved.
The patient in our case was given PCC and vitamin K 10 mg IV. Nasal packing was placed, and his bleeding eventually stopped. He was admitted for observation, and given vitamin K 50 mg orally every six hours. His bleeding stopped on day two, but his INR remained elevated at 6. Brodifacoum levels were obtained and found to be 42 ng/ml. He was discharged home on hospital day three, and prescribed vitamin K 50 mg oral twice a day. He was also given strong bleeding precautions and advised to avoid any physical injury. He continued this treatment for several weeks until his INR levels normalized.
Suggested Readings:
1. Outbreak Alert: Potential Life-Threatening Vitamin K-Dependent Antagonist Coagulopathy Associated with Synthetic Cannabinoids Use. Centers for Disease Control and Prevention, April 5, 2018; http://bit.ly/2JIxOAH.
2. La Rosa FG, Clarke SH, Lefkowitz JB. Brodifacoum intoxication with marijuana smoking. Arch Path Lab Med 1997;121(1):67.
3. Waien SA, Hayes D Jr, Leonardo JM. Severe coagulopathy as a consequence of smoking crack cocaine laced with rodenticide. New Engl J Med 2001;345(9):700.
4. Spahr JE, Maul JS, Rodgers GM. Superwarfarin poisoning: A report of two cases and review of the literature. Am J Hematol 2007;82(7):656.
5. Outbreak Alert Update: Potential Life-Threatening Vitamin K-Dependent Antagonist Coagulopathy Associated with Synthetic Cannabinoids Use. Centers for Disease Control and Prevention, April 23, 2018; http://bit.ly/2Jo62Ky.
