Chan Karen Y T, Zhao Chunyi, Siren Erika M J, Chan Jeanne C Y, Boschman Jeffrey, Kastrup Christian J
Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, and ‡Centre for Blood Research, Department of Pathology and Laboratory Medicine, and the Department of Chemistry, University of British Columbia , Vancouver, BC, Canada.
Biomacromolecules. 2016 Jun 13;17(6):2248-52. doi: 10.1021/acs.biomac.6b00481. Epub 2016 May 17.
The adhesion of blood clots to blood vessels, such as through the adhesion of fibrin, is essential in hemostasis. While numerous strategies for initiating clot formation and preventing clot lysis are being developed to create improved hemostatic agents, strategies for enhancing clot adhesion have not been widely explored. Here, we show that adhesion of blood clots can be increased by adding a previously characterized synthetic polymer that is crosslinked by coagulation factor XIIIa during clotting. Addition of the polymer to normal plasma increased the adhesive strength of clots by 2-fold. It also recovered the adhesive strength of nonadhesive fibrinogen-deficient whole blood clots from <0.06 kPa to 1.9 ± 0.14 kPa, which is similar to the adhesive strength of a fibrinogen-rich clot (1.8 ± 0.64 kPa). The polymer also enabled plasma clots to remain adhered under fibrinolytic conditions. By demonstrating that the adhesive strength of clots can be increased with a synthetic material, this provides a potential strategy for creating advanced hemostatic materials, such as treatments for fibrinogen deficiency in trauma-induced coagulopathy.
血凝块与血管的黏附,比如通过纤维蛋白的黏附,在止血过程中至关重要。虽然目前正在开发多种启动凝血形成和防止凝血溶解的策略,以制造出更有效的止血剂,但增强血凝块黏附的策略尚未得到广泛探索。在此,我们表明,通过添加一种先前已表征的合成聚合物,可增加血凝块的黏附力,该聚合物在凝血过程中由凝血因子XIIIa交联。将该聚合物添加到正常血浆中,可使血凝块的黏附强度提高2倍。它还将无黏附性的纤维蛋白原缺乏全血凝块的黏附强度从<0.06千帕恢复到1.9±0.14千帕,这与富含纤维蛋白原的凝块的黏附强度(1.8±0.64千帕)相似。该聚合物还能使血浆凝块在纤维蛋白溶解条件下保持黏附。通过证明血凝块的黏附强度可用合成材料提高,这为制造先进的止血材料提供了一种潜在策略,比如用于治疗创伤性凝血病中的纤维蛋白原缺乏症。