A sorbent modified with melatonin and lithium: in vitro investigation of the effect on hemostatic reactions

Abstract

Aim of the study was to evaluate the effect of lithium- and melatonin-containing sorbent based on aluminum oxide and polydimethylsiloxane on changes in the number of platelets during hemosorption modeling and on the features of the hemostatic response during dosed contact of the sorbent with blood in an in vitro experiment. Material and methods. An analysis of the effect of the porous sorbent modified with melatonin (MT, 0.15 %) and lithium (0.5 %) based on aluminum oxide and polydimethylsiloxane (Al2O3@PDMS/MT-Li) was carried out in comparison with sorbent without modifiers (Al2O3@PDMS) and modified with MT (Al2O3@PDMS/MT) on a number of donor blood clotting parameters under in vitro hemosorption conditions. Studies of the hemostatic system included assessment of platelet count, chronometric parameters, fibrinogen concentration, antithrombin activity and plasminogen content. For integral assessment, calibrated thrombography and computer thromboelastometry were used. Results and discussion. Contact of all studied sorbents with blood causes a moderate decrease in the number of platelets (by 5.3–10.1 % from initial). Comparison sorbents reduce fibrinogen concentration by 7.1–7.7 %, Al2O3@PDMS/MT-Li – by 2.6 times, which is likely due to the methodology for determining this protein against the background of the independent anticoagulant activity of lithium ions. Al2O3@PDMS and Al2O3@PDMS/MT cause the development of a hypercoagulable shift, as evidenced by a shortening of kaolin time (by 27.5 and 22.1 %, respectively) and of activated partial thromboplastin time (APTT) by 7.1 % for both sorbents. At the same time, when lithium was included in the sorbent, not only did the hypercoagulation shift not occur, but blood clotting was also inhibited, as evidenced by an increase in kaolin time and APTT by 1.2 and 1.6 times, respectively, as well as in silicone time. Conclusions. Modifying sorbents with biologically active substances, lithium and MT, makes it possible to obtain an original hemosorbent with new properties. The presented results demonstrated the absence of a hypercoagulable shift in donor blood after contact with a lithium-, MTcontaining sorbent in vitro and indicate the potential for its using as a basis for the development of safe drugs.

Keywords

• melatonin
• lithium
• aluminum oxide
• polydimethylsiloxane
• sorbent
• platelets
• hemocoagulation
• safety