Phenprocoumon

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.

Ginger-associated overanticoagulation by phenprocoumon

Objective: To report a case of ginger-phenprocoumon interaction resulting in an elevated international normalized ratio (INR) and epistaxis.
Case summary: A 76-year-old white European woman on long-term phenprocoumon therapy with an INR within the therapeutic range began using ginger products. Several weeks later, she developed an elevated INR up to 10 and epistaxis. The INR returned to the normal range after ginger was stopped and vitamin K1 was given.
Discussion: There have been a number of investigations resulting in conflicting opinions on the effect of ginger on hemostasis, specifically, platelet inhibition. Nevertheless, based on these investigations, recommendations have been issued to refrain from ingesting ginger and other herbals like garlic or ginkgo biloba in situations where bleeding may be critical. An objective causality assessment revealed that the adverse drug event as a result of the phenprocoumon and ginger interaction was probable.
Conclusions: As of writing, this was the first case report that may support an interaction between an oral anticoagulant and ginger together with a brief review of the literature on ginger and hemostasis. As this interaction was observed only by chance, this case highlights the importance of self-control of anticoagulation with coumarins particularly for the detection of unknown interactions.

Carbamazepine-phenprocoumon interaction

[Switching from acenocoumarol to phenprocoumon: step in personalised anticoagulation?]

Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.

[Phenprocoumon-associated necrotizing hepatitis]