When a bleeding complication occurs during therapy with heparin or vitamin K 
antagonists, there is an option to give a specific antidote. Several new 
anticoagulants have been developed that are likely to have some risk of bleeding 
complications, for which no specific antidotes are available. Interestingly, it 
is unknown how often the use of an antidote is necessary in clinical practice. 
We investigated 1877 patients treated for venous thromboembolism included in 
three large clinical trials, of which 181 (9.6%) had a total of 225 adjudicated 
bleeding episodes; 46 hemorrhages being designated as major. Some form of 
antidote was given to 26 (14.4%) patients with a hemorrhage. Of the patients 
with at least one major hemorrhage, 19 (41.3%) received an antidote. Vitamin K 
was given to 23 (1.2%) patients, one (0.05%) patient received protamin sulfate 
and seven (0.4%) patients received fresh frozen plasma. The use of antidotes was 
comparable for initial and long-term treatment. Antidotes were statistically 
significantly more frequently given in Canada as compared to other participating 
countries. Vitamin K was more frequently given in case of a higher international 
normalized ratio value. Although antidotes against anticoagulant treatment are 
widely available, our analysis shows that in only a very small number of 
patients a direct, or slow-acting antidote to reverse the anticoagulant effect 
was used.