How I treat poisoning with vitamin K antagonists

Abstract

Severe deficiency of vitamin K–dependent proteins in patients not maintained on vitamin K antagonists is most commonly associated with poisoning by or surreptitious ingestion of warfarin, warfarin-like anticoagulants, or potent rodenticides (“superwarfarins”), such as brodifacoum. Serious bleeding manifestations are common. Superwarfarins are 2 orders of magnitude more potent than warfarin and have a half-life measured in weeks. These rodenticides are readily available household environmental hazards and are sometimes consumed accidentally or as manifestations of psychiatric disease. Immediate diagnosis and proper therapy is critically important to minimize morbidity and mortality because this condition, affecting thousands of patients annually, is reversible. Treatment with large doses of oral vitamin K1, often over months to years, to maintain a near-normal prothrombin time can reverse the coagulopathy associated with superwarfarins. Although these patients initially present to various medical specialties, the hematologist is often consulted to offer the definitive diagnosis and proper therapy.

Brodifacoum Induces Early Hemoglobinuria and Late Hematuria in Rats: Novel Rapid Biomarkers of Poisoning

“…Brodifacoum (BDF) is one of the most commonly used superfarwarins in the USA [1]. The main pathogenic mechanism of BDF action is similar to warfarin, namely a reduction of bioavailable vitamin K resulting in excessive anticoagulation and death.…”

Treatment of a long-acting anticoagulant rodenticide poisoning cohort with vitamin K1 during the maintenance period

“…These results might be attributable to the anticoagulant rodenticide combining with the target of VKOR, [5,7] in which the sustained stimulation of vitamin K1 could increase the expression of VKOR analogs that did not combine with the anticoagulant rodenticides. This would result in a further decrease in vitamin K1 requirements.…”

“…In addition, included patients had no history of liver disease, had an abnormal international normalized ratio (INR) during the treatment period, and were not currently taking any selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), metronidazole, or cimetidine. [5] Patients who consumed alcohol or had hypoproteinemia during the treatment process were excluded from the study.…”

“…[1–3] According to the domestic reports of Wang and Jiang, [4] patients with LAAR poisoning accounted for 18% of all poison cases (772/4289) in Jingdezhen City, Jiangxi Province, China from 1996 to 2005. Internationally, similar poisoning cases [5] registered by American Poison Control Centers in 2012 reached 9555 persons. Aside from the fecal–oral route, the most common route of exposure to anticoagulant rodenticide toxicants is absorption through the skin.…”

“…[7] Clinical examination [8,9] showed that LAARs can significantly prolong prothrombin time (PT) and activated partial thromboplastin time (APTT). The treatment for anticoagulant rodenticide poisoning [5] primarily includes administration of vitamin K1, fresh frozen plasma (FFP), prothrombin complex, and recombinant coagulation factor VIIa. Lubetsky et al [10] proposed that the curative effect of 5 mg vitamin K orally administered is equivalent to 1 mg vitamin K1 intravenously administered.…”