Aptamers influence the hemostatic system by activating the intrinsic coagulation pathway in an in vitro Chandler-Loop model.
One class of oligonucleotides with a high potential for use in medical applications is short nucleic acids, widely known as aptamers. Although several aptamers are already being used clinically, there are very few studies dealing with the impact aptamers have on the hemostatic system. In this study, we have performed a comprehensive evaluation of the hemostatic system including coagulation, platelets, complement, and inflammatory activation by using different aptamer concentrations and fresh human whole blood in a well-established flow model. We found that single-stranded aptamers did not have a negative influence on platelets, complement, or inflammation but were able to activate factor XII, kallikrein, and prothrombin in a concentration-dependent manner. Consequently, the influence of aptamers on the coagulation system should be taken into consideration before the use of any aptamer-based drugs in patients.
Paul
Angela
A
Department of Thoracic, Cardiac, and Vascular Surgery, University Hospital Tuebingen, Calwerstrasse 7/1, Tuebingen, Germany.
Avci-Adali
Meltem
M
Neumann
Bernd
B
Guo
Ketai
K
Straub
Andreas
A
Dietz
Klaus
K
Ziemer
Gerhard
G
Wendel
Hans P
HP
D052157:Aptamers, Nucleotide / Q000494:pharmacology* / Q000633:toxicity; D015415:Biomarkers; D001777:Blood Coagulation / Q000187:drug effects*; D003165:Complement System Proteins / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005174:Factor XII / Q000378:metabolism; D018056:Hemorheology; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D007610:Kallikreins / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D011516:Prothrombin / Q000378:metabolism; D052156:SELEX Aptamer Technique
D052157:Aptamers, Nucleotide; D015415:Biomarkers; D004277:DNA, Single-Stranded; D006629:Hirudins; D011516:Prothrombin; D005174:Factor XII; D006493:Heparin; D003165:Complement System Proteins; D007610:Kallikreins