Adverse effects of coumarin anticoagulants

The biochemistry of vitamin K metabolism and the role of vitamin K-dependent gamma-carboxylation of the vitamin K-dependent coagulation factors are now well understood. Likewise, there is a clear understanding of the role of oral anticoagulants in the inhibition of these coagulation factors. However, the effect of oral anticoagulants on extrahepatic gamma-carboxylated proteins such as osteocalcin and matrix gamma-carboxyglutamate (Gla)-protein (MGP), and the effects of long term anticoagulants on bone mineral metabolism are just now being recognised. The relevance of these observations on mineral metabolism for elderly individuals, and in particular postmenopausal women who are on long term anticoagulants, is still unknown but worthy of continued close observation. The most significant hazard of oral anticoagulants is haemorrhage. Clinical trials continue to demonstrate that less intense (lower dosage) warfarin therapy can significantly decrease this risk of haemorrhage while at the same time providing equal efficacy when compared to more intense warfarin therapy. The more widespread use of the International Normalised Ratio (INR) for the control of anticoagulants will undoubtedly further decrease the risk of haemorrhage, but new innovations such as the use of ultra low-dose warfarin or newer techniques for the continued monitoring of oral anticoagulants are still required, particularly as the indications for oral anticoagulants continue to expand.