35 – Drugs affecting blood coagulation, fibrinolysis, and hemostasis

Publisher Summary This chapter describes the drugs affecting blood coagulation, fibrinolysis, and hemostasis. In a case-control study 170 patients with atrial fibrillation who developed intracranial hemorrhage while taking warfarin were compared with 1020 matched controls that did not. Vitamin K antagonists, such as warfarin, prevent gamma-carboxylation of the vitamin K-dependent procoagulant factors II, VII, IX, and X and the natural anticoagulants protein C and protein S. It is suggested that multiple digital gangrene can result from the interaction of various localizing and systemic factors, including compromised microvascular blood flow, increased thrombin generation, and warfarin-induced failure of the protein C natural anti-coagulant pathway. Genetic Variant alleles of CYP2C9, CYP2C9*2, and CYP2C9*3 are associated with an increased response to warfarin. An effect on acenocoumarol dose requirements appears to be absent for the CYP2C9*2 allele and the consequences for phenprocoumon metabolism have not been established. The reports of azithromycin–warfarin interactions support the possibility that azithromycin does interact with warfarin.