Coumarins anticoagulant activity

Hypoprothrombinemia may occur in malabsorption syndromes and also the use of broad-spectrum antibiotics may produce a hypoprothrombinemia that responds readily to small doses of vitamin K. In premature infants and in infants with hemorrhagic disease of the newborn the use of vitamin K may be indicated. However, the main indication for the use of vitamin K is to antagonize the anticoagulant activity of coumarins. Oral absorption of phytonadione and the menaquinones is by the lymph while menadione and its water-soluble derivatives are absorbed directly. The absorption of phytonadione is energy-dependent and saturable. Intravenous administration of phytonadione has produced flushing, dyspnea, chest pains, and cardiovascular collapse. 

Lamnaouer, D. (1999). Anticoagulant activity of coumarins from Ferula communis L (review). Therapie54(6) 747-51. (In French)... 

Coumarin has no anticoagulant activity, is not used to prevent blood clots, and does not interact with the vitamin K-dependent clotting factors. It is not teratogenic in humans (does not cause hemorrhagic syndrome) and has no reported adverse effects on human reproduction. In contrast to overexposure to Coumadin, coumarin overexposure does not result in bruising and hemorrhage. 

The coumarin anticoagulants, which are orally active, include dicumarol, warfarin sodium (coumadin sodium), warfarin potassium (Athrombokin-K), acenocoumarol (Sintrom), and phenopromcouman (Liquamar). 

A) Activated partial thromboplastin time reliably measures the anticoagulant effect of low-molecular-weight (LMW) heparins Cimetidine increases the anticoagulant activity of warfarin Coumarin anticoagulants reduce the activities of clotting factors 11, VII, IX, and X Heparins are safe to use in the pregnant patient... 

There are no studies of the effect of clarithromycin on the pharmacokinetics or anticoagulant activity of coumarins. However, there are at least 13 cases of increased INRs in published reports, and one cohort study suggesting that the use of clarithromycin is associated with an increased risk of bleeding in patients taking coumarins. These are discussed below. 

Weiner M, Effect of centrally active drugs on the action of coumarin anticoagulants. Nature (1966)212,1599-1600,... 

Chamomile has been indicated as an herb with the theoretical potential for interacting with warfarin due to the coumarin content of the herb (Heck et al. 2000). The cou-marin content, however, consists of the coumarin derivatives herniarin and umbelliferone. Herniarin has been shown to have hemostatic activity (Ahmad and Misra 1997) and umbelliferone has shown no evidence of anticoagulant activity (Egan et al. 1990 Feuer 1974 Pelkonen et al. 1997). The flavonoid apigenin has been shown to inhibit platelet aggregation in vitro (Landolfi et al. 1984 Teng et al. 1985). 

No changes in the anticoagulant activity (thromboplastin time or partial thromboplastin time) of warfarin was observed in rats orally coadministered single doses of 500 mg/kg of Pelargonium sidoides and 0.05 mg/kg of warfarin or in rats orally administered 500 mg/kg daily for 2 weeks prior to administration of a single dose of warfarin. The authors noted that coumarin-type anticoagulants inhibit the synthesis of vitamin K-dependent coagulation factors via identical mechanisms in rats and humans, and have a similar pattern of metabolism in both species (Koch and Biber 2007). 

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