title: Abnormal blood clot formation induced by temperature responsive polymers by altered fibrin polymerization and platelet binding.
abstract: Thermoresponsive polymers (TRPs) have been extensively investigated as smart devices, drug delivery systems and protein conjugates due to their unique phase transition properties. Here, we report the unusual influence of TRPs in blood clotting and the mechanism by which TRPs change the three dimensional organization of blood clot structure. Ten different TRPs with lower critical solution temperatures ranged from 26 to 80 °C are studied. TRPs altered the fibrin polymerization by increasing the rate of protofibril aggregation, decreased the fibrin fiber diameter and changed the platelet integration within the clot. The mechanical properties of the clot decreased considerably in presence of TRPs due to the poor platelet binding. The poor integration of platelets within the clot is not due to the inhibition of platelet activation by TRPs but may due to the unusual organization of fibrin structure. The plasma phase of the blood coagulation is not affected in presence of TRPs. We anticipate that our results will have significant implications on the use of TRPs in applications where blood contact is essential. These observations may also open up new avenues, for example, in the design of new generation antithrombotics.
authors.affiliation: Centre for Blood Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Benjamin F L
authors.initials: BF
authors.lastname: Lai
authors.affiliation: Centre for Blood Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Centre for Blood Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Centre for Blood Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Xifei
authors.initials: X
authors.lastname: Yu
authors.affiliation: Centre for Blood Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Chemistry, University of British Columbia, Vancouver, BC, Canada. Electronic address: jay@pathology.ubc.ca.
authors.forename: Jayachandran N
authors.initials: JN
authors.lastname: Kizhakkedathu
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000737:chemistry*; D005337:Fibrin / Q000737:chemistry*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D015539:Platelet Activation / Q000502:physiology*; D058105:Polymerization; D011108:Polymers / Q000737:chemistry; D011516:Prothrombin / Q000378:metabolism; D013696:Temperature; D013916:Thrombelastography / Q000379:methods; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D011108:Polymers; D011516:Prothrombin; D005337:Fibrin; D013925:Thromboplastin
keywords: Blood clotting; Blood coagulation; Fibrin clot; Fibrin polymerization; Platelet binding; Thermoresponsive polymers