Bleeding coumarin anticoagulants

Bleeding is the major complication of coumarin anticoagulants. The annual incidence of major bleeding among 4060 patients in the AFFIRM trial, who were followed for an average of 3.5 years, was about 2% per year (27). 

There is also a rare ala-10 mutation in the propeptide of factor IX, which leads to an increased risk of bleeding when starting anticoagulation with coumarin anticoagulants (99,100). 

Naproxen should be given with care to patients with asthma or bronchospasm, bleeding disorders, cardiovascular disease, peptic ulceration or a history of such ulceration, renal failure, and in those who are recieving coumarin anticoagulants. Patients who are sensitive to aspirin should generally not be given naproxen (5). 

Increasied anticoagulant effects and bleeding has been seen in patients taking a coumarin anticoagulant or the indanedione, phenindione and an anabolic steroid or testosterone. 

The overall picture is that no adverse interaction normally occurs between these quinolones and coumarin anticoagulants, but rarely and unpredictably increased anticoagulant effects and even bleeding can occur with some of them. There is no need to avoid using any of the quinolones with oral anticoagulants but it would be prudent to monitor the effects when any quinolone antibacterial is first added to treatment with any coumarin so that any problems can be quickly identifred. 

The interaction between co-trimoxazole and coumarin anticoagulants is well documented and well established. The incidence appears to be high. If bleeding is to be avoided the INR should be well monitored and the warfarin, acenocoumarol, or phenprocoumon dosage should be reduced. Anecdotal evidence suggests that co-trimoxazole may not interact with the indanedione phenindione, but note that sulfaphenazole did, so some caution is still appropriate. 

The combination of dipyridamole and coumarin anticoagulants does not alter the prothrombin time, but might cause an increased risk of serious bleeding when compared with anticoagulants alone. There is some evidence that the risk of bleeding may be lower, without a reduction in efficacy, if the INR is maintained within a lower range. 

The principal adverse reaction to warfarin is hemorrhage. Prolonged therapy with the coumarin-type anticoagulants is relatively free of untoward effects. Bleeding may be observable (e.g., skin, mucous membranes) or occult (e.g., gastrointestinal, renal, cerebral, hepatic, uterine, or pulmonary). Rarer untoward effects include diarrhea, small intestine necrosis, urticaria, alopecia, skin necrosis, purple toes, and dermatitis. 

This compound is also of the coumarin family. The fonnula is 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin. In addition to use in anticoagulant therapy in medicine, the compound also has been used as a major ingredient in rodenhcides, where the objective is to induce bleeding and, when used in heavy doses, is thus lethal. The compound can be prepared by the condensation of benzylidene-acetone and 4-hydroxycoumann. 

Warfarin - altered coagulation parameters and/or bleeding have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin. Patients taking warfarin... 

Anthoxanthum odoratum (sweet vernal grass) contains anticoagulant coumarins, which cause bleeding in cattle that consume the grass. 

The first anticoagulant rodenticide was dicoumarin (19). Its anticoagulant effect was first observed on cattle. Coumarin has an odour reminiscent of hay. When mown sweet clover (Melilotus albe) becomes mouldy, dicoumarin is formed from coumarin, and cattle fed with such mouldy, sweet clover hay bleed to deat when injured because of reduced blood coagulation (Campbell and Link, 1941 Stahmann et al., 1941). Dicoumarin, 3,3 -methylene-bis(4-hydroxycoumarin), is obtained by the condensation of 2 moles of 4-hydroxycoumarin (20) and 1 mole of formaldehyde in aqueous solution. 

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