Why is factor Xa not a better target than factor IIa for therapeutic inhibition of coagulation?

The rapid development of new and selective anticoagulant agents has triggered the question of which activated coagulation factor would be a better target for the inhibition of coagulation. Indirect comparisons between studies on the different drugs are problematic due to the plethora of characteristics that may differ between them. Even head-to-head comparisons in the same study may not determine the optimal target due to differences in pharmacokinetics between the agents. Therefore, the answer to this question relies on theoretical speculations based on knowledge of some of the factors that seem to have an influence on efficacy and safety. Ultimately, drugs with equal pharmacokinetic characteristics that are administered in equipotent doses may have a similar global effect on coagulation, independent of the inhibitory mechanism. Conversely, the differentiated inhibition of the coagulation protease on vascular receptors may play a greater role for effects that are not traditionally considered as part of hemostasis.