Case Report

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American Journal of Emergency Medicine

journal homepage: www. elsevier. com/ locate/ajem

Superwarfarin ingestion treated successfully with Prothrombin complex concentrate?,??

Abstract

Superwarfarin, a common component of rat poison, can cause long- lasting, severe coagulopathy and Life-threatening hemorrhage when ingested. We report a case of intentional rat poison consumption with subsequent hemorrhage and hypotension requiring rapid coagulopathy reversal and resuscitation in the emergency department. In addition to traditional blood products, prothrombin complex concentrate was ad- ministered. Although prothrombin complex concentrate is increasingly used for severe hemorrhage in Anticoagulated patients, it may be partic- ularly useful in superwarfarin ingestions given the extreme, persistent coagulapathies that can occur.

A 45-year-old man with known psychiatric disease was brought to our emergency department (ED) by law enforcement after being found with epistaxis and altered mental status. The patient had been noted to be sitting continuously on the same public bench for 2 days. On arrival, the patient was alert and oriented but was extremely tangen- tial and unable to participate in a formal history. He complained only of fatigue. His vital signs were within normal limits, and his complete ex- amination was otherwise notable for oozing of blood from the nares and rectum.

Given his altered mental status and bleeding, an extensive evalua- tion was begun. Laboratory values were notable for a hematocrit of 13%, platelets of 293 K/uL, International normalized ratio of great- er than 10, and a prothrombin time of greater than 200 seconds. A urine toxicology screen, toxic alcohol panel, and acetaminophen and salicy- late levels were all negative. A noncontrast head computed tomography showed no acute process including intracranial hemorrhage.

Given these findings, further directed questioning of the patient was performed, revealing ingestion of rat poison to “rid his body of a danger- ous bacteria.” The patient denied suicidality.

Early in his ED course, the patient became tachycardic and hypoten- sive. Nasal packing was applied, and pantoprazole was given intrave- nously. The patient was transfused with 4 U of Packed red blood cells, 5 U of fresh frozen plasma and 1 U of platelets, improving his blood pressure. Upon discovering his ingestion, 40 mg of vitamin K was given intravenously. Because of his instability and persistent bleed- ing, 45 IU/kg of 4-factor PCC was ordered. He was quickly transferred to an intensive care unit.

? Index Medicus subheadings: coagulopathy, and hemorrhage, Intentional ingestion.

?? This work has not been presented elsewhere. There was no funding or financial support.

The patient received PCC immediately after transfer; subsequent Coagulation studies were normal. These were maintained with daily vitamin K only. The patient was hospitalized involuntarily for ongoing oral vitamin K repletion for 1 month without any throm- botic events.

The active drug class in many rat poisons is superwarfarin (eg, brodifacoum). These vitamin K antagonists are related to warfarin but are 100 times more potent, due to their high Lipid solubility and prefer- ential concentration in the liver [1,2]. Importantly, they are long acting with a half life of up to 30 days (as opposed to 40 hours for warfarin); anticoagulation effects can last for weeks to months [3]. Such poisons are widely available throughout the world.

Vitamin K antagonists inhibit vitamin K epoxide reductase, which replenishes the active form of vitamin K, leading to a deficit in the clotting factors II, VII, IX, and X. Commonly used reversal agents for superwarfarin poisoning include vitamin K, FFP, and prothrombin com- plex concentrate (PCC). Large daily doses of vitamin K can reverse superwarfarin-induced coagulopathy but take at least 12 hours to work so are not effective for active bleeding [4]. Fresh frozen plasma can more quickly replace diminished clotting factors but comes with the risks of a blood transfusion, including infection, transfusion reaction, and volume overload. It requires time to be cross-matched, thawed, and then infused [5]. Four-factor PCC is a lipophilized concentration of the factors antagonized by warfarin that is both rapid and long acting [5]. In cases of significant hemorrhage from coagulopathy in trauma, it is su- perior to FFP [6].

Superwarfarin overdose is a difficult diagnosis to make in the ED, as it often occurs in contexts like intentional poisoning, suicide attempt, Munchausen syndrome, and accidental ingestion by children; key ele- ments of the history are often unavailable in these situations [7]. Some- times, the diagnosis is made only when factor levels remain low after many days of vitamin K replacement [3]. Although there are 2 prior case reports of PCC use in patients after overdose, both occurred well into hospital admission [3,8].

In this case, the patient’s extremely high INR coupled with his men- tal illness and lack of known access to warfarin made us suspect rat poi- son ingestion. When a potential for this type of ingestion is coupled with ongoing bleeding, PCC may be a better choice than FFP, even in a hemo- dynamically stable patient. In 1 superwarfarin case report, FFP infusions were required for days to maintain hemostasis [7]. And prior studies looking at coagulopathies more broadly have shown that PCC alone or in addition to FFP leads to a more consistent and long-acting normalized INR as well as Hemorrhage control [9,10].

To our knowledge, this is the first case of PCC-reversed superwarfarin overdose initiated in the ED. We believe that such poi- sonings and the use of PCC for reversal should be considered in all

0735-6757/(C) 2015

cases where extreme INR values are obtained without a clear explana- tion for the abnormality.

Olivia Haesloop, MD Division of Emergency Medicine University of Washington School of Medicine, Seattle, WA

Allison Tillick, MD Graham Nichol, MD

Department of Medicine, University of Washington School of Medicine

Seattle, WA

Jared Strote MD, MS Division of Emergency Medicine University of Washington School of Medicine, Seattle, WA Corresponding author. Division of Emergency Medicine University of Washington Medical Center

Box 356123 1959 NE Pacific St, Seattle, WA 98195 Tel.: +1 206 598 0103; fax: +1 206 598 4569

E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2015.05.033

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