Successful Reversal of Anticoagulant Effect of Brodifacoum Poisoning with 4-Factor Prothrombin Complex Concentrate (PCC4)

Case Report

Austin J Pharmacol Ther. 2017; 5(2).1092.

Successful Reversal of Anticoagulant Effect of Brodifacoum Poisoning with 4-Factor Prothrombin Complex Concentrate (PCC4)

Kusmierski KA*, Lackie CL and Scull JR

Department of Pharmacy, Millard Fillmore Suburban Hospital, USA

*Corresponding author: Kusmierski KA, Department of Pharmacy, Millard Fillmore Suburban Hospital, USA

Received: March 17, 2017; Accepted: April 05, 2017; Published: April 11, 2017

Abstract

Title: Successful reversal of anticoagulant effect of brodifacoum poisoning with 4-factor prothrombin complex concentrate (PCC4).

Introduction: Brodifacoum is a long-acting anticoagulant rodenticide that is similar to warfarin, but significantly more potent with prolonged half-life and potential for severe coagulopathy.

Case: A 43-year-old woman presented to the emergency department with non-traumatic bruising, abdominal pain, and hematuria. Initial evaluation revealed a severe coagulopathy and international normalized ratio (INR) greater than 13. PCC4 (Kcentra®) 25units/kg, phytonadione, and fresh frozen plasma (FFP) were administered with improvement in INR without additional intervention to control bleeding. A rebound increase in INR occurred within 24 hours. Brodifacoum toxicity was confirmed (brodifacoum level=300ng/mL) after patient admitted to possible cutaneous and aerosolized exposure to “rat poison.” The patient required FFP and high doses of phytonadione to control coagulopathy throughout her admission. She was discharged on phytonadione.

Discussion: PCC4 administration improved coagulation parameters rapidly with control of bleeding and no adverse effects. The rebound in coagulation parameters demonstrated the continued need for treatment of coagulopathy while awaiting confirmation of brodifacoum poisoning.

Conclusion: This case illustrates successful acute reversal of brodifacoum poisoning with Kcentra®, phytonadione, and FFP. In this patient, the addition of PCC4 rapidly reversed her severe coagulopathy without adverse events.

Keywords: Brodifacoum; Superwarfarin; Poisoning; Prothrombin complex concentrate; Bleeding; Rat poison

Introduction

Superwarfarins, a class of rodenticide, were developed to overcome resistance to warfarin in rodents. These long-acting anticoagulant rodenticides (LAARs) are highly lipid soluble with a longer duration of action and much greater potency than warfarin [1,2]. Brodifacoum, the most commonly used LAAR, is 100-fold more potent than warfarin, has a half-life of 16-36 days, and its anticoagulant effect may continue even after it is no longer measurable in the serum [3].

Due to the accessibility of superwarfarin compounds, both unintentional and intentional exposures have been reported. Standard treatment of superwarfarin poisoning involves the use of fresh frozen plasma (FFP) and phytonadione in the acute period, followed by long-term phytonadione administration until the LAAR effects resolve [1]. We describe a case of severe coagulopathy with bleeding due to brodifacoum poisoning successfully treated with 4-factor prothrombin complex concentrate (PCC4), Kcentra® (CSL Behring GmbH, Germany).

Case Presentation

A 43-year-old woman presented to the Emergency Department (ED) with a one week history of non-traumatic bruising on her lower extremities and distal upper extremities, right lower abdominal pain, and hematuria. Her medical history was significant for cauda equine syndrome following a traumatic spine injury and mixed mood disorder. Her home medications included baclofen, diazepam, diclofenac topical patch, gabapentin, hydrocodone/acetaminophen, omeprazole, multivitamin, and vortioxetine. She was a nonsmoker, denied recreational drug use, and admitted to only occasional social use of alcohol.

On admission, laboratory values revealed a severe coagulopathy which included an international normalized ratio (INR) greater than 13, prothrombin time (PT) greater than 100 seconds, and an activated partial thromboplastin time (aPTT) greater than 200 seconds. Her fibrinogen level was slightly elevated at 508mg/dL. Initial complete blood count (CBC) did not demonstrate anemia or thrombocytopenia with hemoglobin of 13.9g/dL, hematocrit of 40.4%, and platelet count of 218 x 109/L. Liver function tests and renal function was grossly normal. Urine toxicology screen was positive for benzodiazepines which was consistent with diazepam use prior to admission. Clotting factor studies were not obtained. Pertinent physical exam findings included a large hematoma in the right upper retromolar region, mild to moderate tenderness to palpation in the suprapubic and right lower quadrant region, multiple ecchymoses on her thighs and scattered on her distal lower extremities, and large ecchymoses involving the radial surfaces of the wrists bilaterally. A computerized tomography scan of the abdomen and pelvis demonstrated a retroperitoneal, intrarenal, perirenal, and pararenal hemorrhage. She denied a history of bleeding or clotting disorders as well as anticoagulant or overthe- counter (OTC) supplement use, any new medications, or OTC pain reliever used in excess. She denied the possibility of overdose of another family member’s warfarin, which was in the house.

Phytonadione, fresh frozen plasma (FFP), and PCC4 (Kcentra®) 25IU/kg (actual 23.4IU/kg, rounded to nearest vial size) were administered in the ED with initial improvement in coagulation laboratory values (INR=1.31, PT=15.8 seconds, and aPTT=35 seconds three hours post PCC4 administration), but a rebound increase occurred within 24 hours (Figure 1). The patient remained hemodynamically stable. Wanting to rule out warfarin toxicity, a warfarin level was drawn on hospital day two for completeness and resulted back without detection four days later. Brodifacoum toxicity was suspected after patient, on hospital day number three, admitted to cutaneous contact with “rat poison” about three weeks prior to admission after spilling it and sweeping it up by hand on two occasions. She also described possible aerosolized contact as she placed open bait beneath her bed. A brodifacoum level was drawn on hospital day four, sent to an outside laboratory, and resulted 20 days later which confirmed brodifacoum toxicity (brodifacoum level=300ng/mL). Patient required seven units of FFP and doses of up to 40mg/day of phytonadione to control coagulopathy throughout her twelve day admission. She was discharged on oral phytonadione 20mg daily with close follow-up with a hematologist. No thrombotic events occurred during her 12 day hospital stay.

Citation: Kusmierski KA, Lackie CL and Scull JR. Successful Reversal of Anticoagulant Effect of Brodifacoum Poisoning with 4-Factor Prothrombin Complex Concentrate (PCC4). Austin J Pharmacol Ther. 2017; 5(2).1092. ISSN: 2373-6208.