G-quadruplex based DNA aptamers for human thrombin are promising pharmaceuticals as anticoagulants. Initially discovered 15-mer DNA aptamer (15-TBA) has a minimal G-quadruplex structure which is able to inhibit thrombin. 15-TBA was modified and extended to improve aptamer activity and in vivo stability providing 31-TBA, NU172, RA-36, and some others as successful examples. In this paper an interplay between G-quadruplex (pharmacophore module) and additional modules has been studied. An original turbidimetric assay and conventional coagulation tests were applied to evaluate both inhibitory activity and type of inhibiting for aptamers constructed by exchanging the modules between 31- TBA and NU172. Additional modules strongly affect pharmacophore module inhibitory activity either enhancing or reducing it. RA-36 aptamer has two putative pharmacophore entities which also interplay being functionally non-equal. 5’- truncated RA-36 has half of the activity of RA-36, and the same as for 15-TBA. On the contrary 3’-truncated RA-36 has intermediate activity in between 15-TBA and RA-36. These results indicate fine regulation of G-quadruplex inhibitory activity by additional modules, as well as non-trivial behavior of joined pharmacophore modules.