vitamin-k-1 and Drug-Overdose

We cared for a patient who ingested an unknown amount of acetaminophen with zopiclone and warfarin. The only liver function test that was abnormal was an increased international normalized ratio (INR), which remained elevated despite treatment with subcutaneous phytonadione and a prolonged infusion of N-acetylcysteine. An interaction between acetaminophen and warfarin may have decreased the hepatic metabolism of warfarin. The patient received numerous antibiotics that may have contributed to the increased INR. The prolonged elevation of INR also may have been due to infrequent administration of phytonadione.

Topics: Acetaminophen; Acetylcysteine; Aged; Analgesics, Non-Narcotic; Anti-Bacterial Agents; Anticoagulants; Antidotes; Antifibrinolytic Agents; Azabicyclo Compounds; Charcoal; Drug Interactions; Drug Overdose; Female; Gastric Lavage; Humans; Hypnotics and Sedatives; International Normalized Ratio; Piperazines; Vitamin K; Vitamin K 1; Warfarin

Topics: Acute Disease; Combined Modality Therapy; Drug Overdose; Ergot Alkaloids; Female; Humans; Infant, Newborn; Medication Errors; Methylergonovine; Splanchnic Circulation; Vitamin K 1

Guidelines exist on the management of supratherapeutic/subtherapeutic international normalized ratio (INR) values for patients on warfarin. However, there is a paucity of the literature relating to an acute overdose of warfarin. This is a retrospective cohort study for all acute and acute-on-chronic (AOC) warfarin overdoses reported to the Maryland Poison Center in patients ≥12 years between January 1st, 2000, until October 31st, 2019, managed in a health care facility. The primary outcome was to determine the time after presentation to peak INR. Secondary outcomes included risk factors associated with INR >10 and describing patient characteristics. A total of 163 overdoses were included, 68 acute and 95 AOC. In patients who did not receive reversal therapies, INR peaked at a median value of 3.8 (interquartile range 2.6-5.5) between 24 and 36 hours. The median time to phytonadione was 22.0 hours. Most patients received phytonadione (62.0%), with fewer receiving blood products (16.6%). The median warfarin dose ingested was 75 mg. The AOC group had a greater mean age (56 vs. 43 years), median INR value (2.4 vs. 1.4), and men (62.1% vs. 41.2%). Factors associated with an INR > 10 included initial INR and reported quantity ingested. Peak INR was greater in the AOC than the acute overdose group (6.1 vs. 3.4), although the bleeding rate was similar. Peak INR values after warfarin overdose occur between 24 and 36 hours after presentation. Initial INRs and reported quantity ingested may be useful to predict those needing treatment.

Topics: Adult; Aged; Anticoagulants; Antidotes; Antifibrinolytic Agents; Blood Coagulation; Drug Overdose; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Maryland; Middle Aged; Poison Control Centers; Predictive Value of Tests; Retrospective Studies; Time-to-Treatment; Vitamin K 1; Warfarin

Topics: Anticoagulants; Antidotes; Drug Overdose; Emergency Service, Hospital; Factor VIIa; Female; Humans; International Normalized Ratio; Middle Aged; Recombinant Proteins; Suicide, Attempted; Vitamin K 1; Warfarin

Difenacoum is a long-acting superwarfarin-type anticoagulant that exerts its effect through inhibiting vitamin K 2,3-epoxide reductase. Inhibition of this enzyme leads to reduced bioavailability of the metabolically active form of vitamin K resulting in decreased production of vitamin K-dependent proteins including coagulation factors II, VII, IX and X. A 45-year-old woman with psychiatric illness presented with haematuria. Laboratory test results indicated she had been exposed to a vitamin K antagonist which was subsequently identified as difenacoum. She was initially treated with phytomenadione, red cell suspension and octaplex. She was discharged on 30 mg phytomenadione daily but monitoring of vitamin K markers indicated that compliance was poor, and 152 days post-admission she presented with haemoptysis. Difenacoum and other superwarfarin rodenticides are freely available for purchase by the public. Cases such as this continue to raise issues about their availability and regulation.

Topics: 4-Hydroxycoumarins; Blood Coagulation Factors; Drug Overdose; Erythrocyte Transfusion; Female; Hematuria; Hemoptysis; Humans; Medication Adherence; Mental Disorders; Middle Aged; Rodenticides; Vitamin K 1; Vitamin K Epoxide Reductases

Ingestion of bromadiolone can lead to prolonged and life-threatening coagulopathy. Traditional treatment of bromadiolone intoxication relies on the coagulation profile. Currently, there is scanty information on bromadiolone elimination kinetics and half-life.. We report a case of bromadiolone poisoning in a 40-year old female who, by history, ingested four 42.5-gram bags of rat poison (0.005% bromadiolone), equivalent to 8.5 mg bromadiolone (0.17 mg/kg body weight), four days prior to admission. On admission, her prothrombin time was 92.0 seconds, international normalized ratio was 5.7, and activated partial thromboplastin time was 50.2 seconds with no bleeding on clinical examination. The first plasma bromadiolone level (5 days post-ingestion) was 92 ng/mL. Serial measurement of plasma bromadiolone levels confirmed the diagnosis and demonstrated that bromadiolone obeys the elimination kinetic of a two-compartment model with a rapid, fairly steep decline phase (half-life 3.5 days) followed by a slower termination phase (half-life 24 days). Plasma bromadiolone level of less than 10 ng/mL in our patient was associated with a consistently normal coagulation profile without vitamin K1 therapy.. There is a lack of information on the toxicodynamics and toxicokinetics of bromadiolone in humans; further studies are needed before the plasma bromadiolone level can serve as one of the logical and safe therapeutic endpoints for vitamin K1 therapy.

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Blood Coagulation Tests; Chromatography, Liquid; Drug Administration Schedule; Drug Monitoring; Drug Overdose; Female; Half-Life; Humans; Models, Biological; Rodenticides; Spectrometry, Mass, Electrospray Ionization; Suicide, Attempted; Tandem Mass Spectrometry; Vitamin K 1

Topics: Acenocoumarol; Administration, Oral; Ambulatory Care; Anticoagulants; Antifibrinolytic Agents; Drug Overdose; Follow-Up Studies; Humans; International Normalized Ratio; Treatment Outcome; Vitamin K 1; Warfarin

A 33-year-old man was admitted 8 hours after voluntary ingestion of 1875 mg of chlorophacinone (C'Operat 750 mL). The examination revealed excitation and nausea, with a normal prothrombin index (PI). Comprehensive testing for abused and therapeutic drugs in blood confirmed chlorophacinone (maximum plasma level: 27.6 mg/L), an antivitamin K (AVK) rodenticide. In a search for easy toxicological management of chlorophacinone poisoning treated by phytomenadione and a cytochrome P450 inducer (phenobarbital), PI and chlorophacinone plasma levels were monitored concomitantly during 17 days. A simple HPLC procedure for the determination of chlorophacinone in human plasma is reported for that purpose. Under phenobarbital 200 mg/day, chlorophacinone exhibited an apparent elimination half-life (3.27 days) shorter than in previously reported cases. If PI is useful for planning phytomenadione treatment and used for therapeutic monitoring of AVK, the chlorophacinone concentrations follow-up may provide a better estimation of the duration of hospitalisation. Chlorophacinone accumulation in target cells or existence of an unidentified metabolite may explain persistence of the hypocoagulability syndrome at low plasmatic concentrations of chlorophacinone. This case illustrates how toxicological management may facilitate toxicokinetics and therapeutic data acquisition.

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Tests; Chromatography, High Pressure Liquid; Drug Monitoring; Drug Overdose; Emergency Treatment; Humans; Indans; Male; Substance Abuse Detection; Suicide, Attempted; Vitamin K 1

Topics: 4-Hydroxycoumarins; Adult; Drug Overdose; Factitious Disorders; Female; Humans; Prothrombin Time; Vitamin K 1