Introduction
An anticoagulant called Warfarin, a vitamin K antagonist, treats and prevents several coagulopathic and thromboembolic illnesses. Although it was first advertised as a rodenticide, it has been prescribed as medicine for more than 50 years. Furthermore, Superwarfarins, which are 100 times more toxic than Warfarin and are already used as pesticides, should be regarded as compounds capable of causing Warfarin poisoning.
There are many ways that toxicity could manifest itself:
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Intentional overdose in adults.
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Unintended toxicity.
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Ingestion in children.
The intentional overdose may be the most noticeable. Nonetheless, it has been observed to be extremely infrequent, with one 25-year evaluation of two tertiary hospitals with toxicology capabilities discovering 22 non-pediatric purposeful overdoses. Unintentional toxicity or overdose can develop for a variety of causes, including changes in diet, drug interactions, and even secondary to metastatic liver disease. The initial dose phase presents a specified interval of probable toxicity and risk based on the patient's genetic variants and potentially known circumstances, such as their specific comorbidities and nutrition. Warfarin toxicity can occur as a result of pediatric ingestion, which can occur when a youngster accidentally consumes a pill while exploring or as a result of Munchausen syndrome by proxy. In addition to the techniques mentioned above of intoxication, reports of warfarin toxicity due to Superwarfarins being laced with illegal narcotics to prolong euphoric effects have also been made.
What Is the Etiology of Warfarin and Superwarfarin Toxicity?
Before being developed as a pharmaceutical, Warfarin was first employed as a pesticide. The creation of Superwarfarins, now widely used in homes and businesses as a rodenticide and may expose people, was prompted by the discovery of resistance in rats. As a result, exposures to or poisonings from medicines with the Superwarfarin designation have increased, with cases rising from about 5,000 in 1988 to over 13,000 in 1995.
What Is the Epidemiology of Warfarin and Superwarfarin Toxicity?
766 single exposures to prescription warfarin were recorded in 2014, according to the National Poison Data System Annual Report of the American Association of Poison Control Centers. 355 of those were ingested by children under six. The overwhelming majority (84 %) of prescription warfarin ingestions were accidental overdoses. There were 16 serious clinical episodes described, although none of them were fatal.
181 individuals were exposed to Superwarfarin rodenticides in the same year. In contrast to Warfarin prescribed by a doctor, a significant number (142) of these ingestions were made by young children. It was decided that 170 exposures were unintentional. There were no deaths or significant clinical events reported.
What Is the Toxicokinetics (How the Body Handles a Chemical) Of Warfarin and Superwarfarin Toxicity?
Whether or not specific Superwarfarin agents were consumed, as opposed to Warfarin itself, substantially impacts the toxicokinetics.
Similar underlying pathophysiology to Warfarin dosage is evident in Warfarin toxicity related to chronic overdose. Unfortunately, there are few detailed descriptions of the toxicokinetics of an acute overdose in the literature. Warfarin typically has a T 1/2 (half-life) of 36 to 42 hours, a time-to-peak effect of 36 to 72 hours, and a duration of two to five days after stopping the medication. In addition, it has been documented that an acute Warfarin overdose may result in a potential delay of PT/INR (prothrombin time/ international normalized ratio) increase for 12 hours after intake and coagulopathy that may manifest up to nine days after administration.
The link to clinical signs and problems is one challenging component of toxicokinetics. Even though the INR can be monitored as a sign of coagulopathy, issues from taking Warfarin do not always happen at a certain level. Only one significant bleeding event, no thrombotic events, and no fatal events were discovered in one investigation of acute overdoses, including numerous patients who had an INR greater than ten.
The potential for rebound toxicity is another challenging factor to consider when considering toxicokinetics. There have been case reports of individuals who presented to the hospital for readmission three days after discharge with bleeding episodes and a supratherapeutic INR while being treated for acute Warfarin toxicity with vitamin K and INR normalization. Patients with renal insufficiency are not thought to be at a higher risk of toxicity than the general population because the cytochrome C-450 pathway metabolizes Warfarin in the liver. To attain therapeutic INRs, patients with renal impairment reportedly needed lower doses than the general population.
Patients with possible hepatic dysfunction may experience an unpredictable clinical course, unlike those with renal failure or insufficiency. Although Warfarin has a T 1/2 of 36 to 42 hours, liver illness or alcohol use can significantly influence these statistics. According to studies, continued alcohol use may increase Warfarin metabolism, whereas acute alcohol consumption may induce a reduction.
What Is the History of Warfarin and Superwarfarin Toxicity?
As with most drug toxicities, questions about the kind of medication taken, any concurrent ingestions (such as those of narcotics or alcohol), current medications, the dosage, the time, and the intent should be asked. It is important to record any recent history of trauma, especially to the head. In cases of Warfarin toxicity, it is crucial to determine if the patient is taking Warfarin for a secondary ailment. If so, the person may need to weigh the danger of reversing the INR. Asking about any indications or symptoms of abnormal bleeding, such as nosebleeds, dark urine, or dark stools, is particularly crucial. This information will be crucial in determining the best clinical course of action.
What Is the Treatment Given for Warfarin and Superwarfarin Toxicity?
Depending on several clinical criteria, the treatment and management of patients who present with Warfarin toxicity might vary substantially. INR > 1.4 is the criteria for coagulopathy in these recommendations. INR > 3.0 or >3.5 in a patient with a mechanical heart valve is the definition of warfarin toxicity. Unintentional toxicity in patients receiving Warfarin treatment for a comorbid disease.
The following list of suggested treatments is for a patient who is not experiencing substantial bleeding:
Patients without bleeding should not be given prothrombin complex concentrate (PCC). Warfarin or Superwarfarin intentional consumption in patients not taking anticoagulation:
Regardless of the stated amount ingested, any patient who intentionally consumed Warfarin or Superwarfarin deserves a thorough review. Patients should have their PT/INR and PTT measured at the initial presentation. Patients should have repeated INR evaluations every 12 to 24 hours for acute exposures. In general, no additional testing is required if the INR is still normal after 36 hours and there are no visible signs of bleeding. Vitamin K should only be started in patients with elevated INR who show signs of coagulopathy during evaluation once the INR is greater than ten or there is evidence of bleeding.
Conclusion
The best way to treat Warfarin toxicity is through an interprofessional team. Doctors must inform patients about the importance of monitoring their diet and dosage closely. Doctors, including pharmacists, are also accountable for ensuring the patient is not taking additional medications that could negatively interact with Warfarin. Also, nursing can help identify dangers during patient visits and raise issues with the prescriber or pharmacist. Switching to the more recent oral anticoagulants may be an option for patients who are considered to be at high risk for Warfarin toxicity.
