Massive intoxication with rivaroxaban, phenprocoumon, and diclofenac: A case report.

RATIONALE: Oral anticoagulants and painkillers, some with an additional effect on the coagulation system, are widely used and are therefore prone to abuse and (intentional) overdose. We report the case of a patient with a massive mixed anticoagulant intoxication. PATIENT CONCERNS: The patient had ingested 1960 mg rivaroxaban, 31.5 mg phenprocoumon, 1425 mg diclofenac, and 21,000 mg metamizole in suicidal intention. DIAGNOSES: Massive mixed anticoagulant overdose. INTERVENTIONS: The patient was closely monitored. The phenprocoumon overdose was treated by the administration of vitamin K and PCC. OUTCOMES: Despite the massive inhibition of the coagulation system, the patient did not experience bleeding apart from a slight gross hematuria. LESSONS: Despite the ingestion of a massive amount of rivaroxaban, the plasma levels were not as high as feared, due to the ceiling effect of rivaroxaban absorption. Elimination occurred according to the half-life of rivaroxaban and was not unduly prolonged by the ingested quantity.

[Successful therapy of phenprocoumon poisoning with plasmapheresis]. / Erfolgreiche Therapie einer Phenprocoumon-Intoxikation mit Plasmapherese.

UNLABELLED: A case report demonstrates a possibility of successful treatment in a patient with high-dosage phenprocoumon intoxication. CONCLUSION: The use of plasmapheresis is an appropriate method to treat phenprocoumon-intoxicated patients by exchange of endogenous with supplied fresh frozen plasma.

[46-year-old woman with multiple hematomas and bleeding of the base of the tongue: phenprocoumon poisoning]. / 46jährige Frau mit multiplen Hämatomen und Zungengrundblutung: Phenprocoumon-Intoxikation.

A 46-year old nurse complaining of multiple hematomas including bleeding into the tongue was referred for hemostasis evaluation. A very low Quick percentage value, i.e. a severely prolonged prothrombin time with severely depressed vitamin K-dependent coagulation factors (FII:C, FVII:C, FX:C) and normal FV:C and fibrinogen level was found. In the absence of cholestasis, malabsorption and broad-spectrum antibiotic therapy, ingestion of vitamin K antagonists was suspected. Three years previously, she had been on oral anticoagulant treatment with phenprocoumon (Marcoumar) for postoperative pulmonary embolism. She denied having voluntarily ingested anticoagulant drugs. A high plasma level of coumarins was found. To exclude accidental ingestion, the patient's son living in the same household was tested as well. Surprisingly, a low level of coumarin was found also in his plasma. We suspect that the patient voluntarily intoxicated herself and gave a low dose of coumarin anticoagulant to her son as well.

[Case report. Phenprocoumon (Marcumar, Falithrom) as an unusual reason for coumarin poisoning in a dog]. / Phenprocoumon (Marcumar, Falithrom) als ungewöhnliche Ursache einer Kumarinvergiftung beim Hund.

Coumarin poisoning in dogs is not unusual and is in most cases caused by warfarin, a coumarin derivative which is used as a rodenticide. Competitive inhibition of vitamin K with an incomplete synthesis of the coagulation factors II, VII, IX and X can lead to a significant bleeding tendency. We observed a 3-year old male West Highland White Terrier with a reduced general condition and dyspnoea together with a massive haemothorax. Administration of vitamin K1 (3 mg/kg) led to a rapid improvement of the condition. Coagulation analysis revealed a prolonged activated recalcification time (ARCT), prothrombin time (PT) and aPTT with uncharacteristic thrombin time (TT); factor II, VII and X activities were reduced while factor V activity was normal, all of which are characteristic for coumarin poisoning. HPLC did not reveal the presence of warfarin but of phenoprocoumon, a drug used for thromboembolic prophylaxis in humans. This observation has not been described for dogs to date.

Phenprocoumon poisonings.

Phenprocoumon is a derivative of coumarin, used as a preventative anticoagulant and in the treatment of thromboembolisms. On account of its pharmacodynamic and pharmacokinetic properties, strict surveillance of the patient is necessary. We report on two cases of undocumented administration of this active pharmaceutical ingredient. A 57-year-old woman was discovered by her husband in an inanimate state. The post-mortem examination revealed many extensive haematomas. On account of a suspicion of third-party negligence, an autopsy was performed the same day, during which was established that the cause of death was a clotting abnormality, the cause of which remained unclear. Toxicological analyses revealed a concentration of phenprocoumon of 7.8 mg/l. A 76-year-old man admitted himself to hospital immediately upon returning from a stay abroad. In hospital, extensive haematomas and a massive clotting abnormality (prothrombin ratio<10%) were discovered. A blood sample taken the following day yielded evidence of a phenprocoumon concentration of 3.1 mg/l. According to his general practitioner, no corresponding medications had been prescribed. Suspicion of foul play in the introduction of this active agent resulted in a police investigation. Both cases demonstrate the necessity of toxicological analyses in cases of clotting abnormalities.

[Observations in phenprocoumon (Marcumar) poisoning. Elimination and serum binding of the anticoagulant atatoxic blood concentration]. / Beobachtungen bei Phenprocoumon-(Marcumar-) Vergiftung. Elimination und Serumbindung des Antikoagulans bei toxischen Blutkonzentrationen.

Serial serum concentrations of phenprocoumon were measured in 2 female patients who had taken 150 and 450 mg of the drug in suicidal attempts. In one case absorption of phenprocoumon took nearly two days. At a concentration of 1.7 and 1.8 microgram/ml the elimination curve showed a notch in both patients. Above this concentration half life was 97.7 and 95.9 hours, below these levels 134.4 and 155.5 hours. In-vitro binding investigations with serum of a healthy proband showed an increase of the non-bound drug by 56.6% at a phenprocoumon concentration of 0.5-25.34 micrograms/ml. As no notch could be observed at lower concentrations the notch in the elimination curve cannot be explained by concentration-dependent plasma binding of the anticoagulant. In-vitro experiments involving haemodialysis indicate that the letter cannot be recommended for treatment of phenprocoumon intoxication as the amount of phenprocoumon thus eliminated from the body is minimal. Both patients survived the phenprocoumon intoxication without damage. They were only treated with vitamin K.

[Attempted murder with phenprocoumon (marcumar)(author's transl)]. / Mordversuch mit Phenprocumon (Marcumar). Krankenschwester verursacht "familiäre Blutungsneigung"

The first known case of attempted murder by means of a coumarine-containing drug, administered by a nurse to her husband, is reported. Small doses of phenprocoumon were regularly added to his food or drinks. He was admitted to hospital with a severe haemorrhagic diathesis which, at first, was thought to be a familial haemorrhagic disease, his mother having died of recurrent hypoprothrombinaemia a few years earlier, the cause of her bleeding trouble never having been established. The wife was sentenced to eight years imprisonment.

Fatal cerebellar haemorrhage due to phenprocoumon poisoning.

A 32-year-old patient died of a cerebellar haemorrhage and the blood coagulation analysis before death suggested defective synthesis of vitamin K-dependent clotting factors due to vitamin K deficiency. The post-mortem toxicological examination of different tissues revealed phenprocoumon poisoning as the cause of death. The differential diagnosis of vitamin K deficiency and the toxicology of hydroxycoumarins are discussed.