The influence of poly-N-[(2,2-dimethyl-1,3-dioxolane)methyl]acrylamide on fibrin polymerization, cross-linking and clot structure.
Poly-N-[(2,2-dimethyl-1,3-dioxolane)methyl]acrylamide (PDMDOMA) is a neutral synthetic water-soluble polymer. In this report, we evaluated the influence of PDMDOMA on blood hemostasis by studying the fibrin polymerization process, the three-dimensional clot structure, and the mechanical properties and fibrinolysis. PDMDOMA altered the normal fibrin polymerization by changing the rate of protofibril aggregation and resulting in a 5-fold increase in the overall turbidity. Fibrin clots formed in presence of PDMDOMA exhibited thinner fibers with less branching which resulted in a more porous and heterogeneous clot structure in scanning electron micrographs. The overall strength and rigidity of the whole blood clot also decreased up to 10-fold. When a combination of plasminogen and tissue-plasminogen activators were included in clotting reactions, fibrin clots formed in the presence of PDMDOMA exhibited highly shortened clot lysis times and was supported by the enhanced clot lysis measured by thromboelastography in whole blood. Further evidence of the altered clot structure and clot cross-linking was obtained from the significant decrease in d-dimer levels measured from degraded plasma clot. Thus, PDMDOMA may play an important role as an antithrombotic agent useful in prophylactic treatments for thrombosis by modulating fibrin clot structure to enhance fibrinolysis.
Lai
Benjamin F L
BF
Department of Pathology and Laboratory of Medicine, Centre for Blood Research, Canada.
Zou
Yuquan
Y
Brooks
Donald E
DE
Kizhakkedathu
Jayachandran N
JN
D000178:Acrylamides / Q000378:metabolism*; D001672:Biocompatible Materials / Q000378:metabolism*; D001777:Blood Coagulation; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D011108:Polymers / Q000378:metabolism*; D013916:Thrombelastography
D000178:Acrylamides; D001672:Biocompatible Materials; D005338:Fibrin Fibrinogen Degradation Products; D011108:Polymers; C036309:fibrin fragment D; C551656:poly-N-((2,2-dimethyl-1,3-dioxolane)methyl)acrylamide; D005337:Fibrin