- This study uses a lepirudin based human whole blood model to investigate the coagulation potentials of alginate-based microspheres: alginate microbestemic administration (Ca/Ba Beads), alginate poly-l-lysine microcapsules (APA and AP microcapsules) and sodium alginate-sodium cellulose sulfate-poly(methylene-co-cyanoguanidine) microcapsules (PMCG microcapsules).
- Coagulation activation measured by prothrombin fragments 1+2 (PTF1.2) was rapidly and markedly induced by the PMCG microcapsules, delayed and lower induced by the APA and AP microcapsules, and not induced by the Ca/Ba Beads.
- Monocytes tissue factor (TF) expression was similarly activated by the microcapsules, whereas not by the Ca/Ba Beads. PMCG microcapsules-induced PTF1.2 was abolished by FXII inhibition (corn trypsin inhibitor), thus pointing to activation through the contact pathway.
- PTF1.2 induced by the AP and APA microcapsules was inhibited by anti-TF antibody, pointing to a TF driven coagulation.
- The TF induced coagulation was inhibited by the complement inhibitors compstatin (C3 inhibition) and eculizumab (C5 inhibition), revealing a complement-coagulation cross-talk.
- Conclusion: This is the first study on the coagulation potentials of alginate microspheres, and identifies differences in activation potential, pathways and possible intervention points.
Authors: Gravastrand C, Hamad S, Fure H, Steinkjer B, Ryan L, Oberholzer J, Lambris JD, Lacík I, Mollnes TE, Espevik T, Brekke OL, Rokstad AM.
Reference: Acta Biomater. 2017 Aug;58:158-167. doi: 10.1016/j.actbio.2017.05.052. Epub 2017 May 30.