Smith Stephanie A, Morrissey James H
Departments of Internal Medicine and Biochemistry, College of Medicine, University of Illinois at Urbana-Champaign, USA.
Blood. 2008 Oct 1;112(7):2810-6. doi: 10.1182/blood-2008-03-145755. Epub 2008 Jun 10.
Polyphosphate, a linear polymer of inorganic phosphate, is present in platelet dense granules and is secreted on platelet activation. We recently reported that polyphosphate is a potent hemostatic regulator, serving to activate the contact pathway of blood clotting and accelerate factor V activation. Because polyphosphate did not alter thrombin clotting times, it appeared to exert all its procoagulant actions upstream of thrombin. We now report that polyphosphate enhances fibrin clot structure in a calcium-dependent manner. Fibrin clots formed in the presence of polyphosphate had up to 3-fold higher turbidity, had higher mass-length ratios, and exhibited thicker fibers in scanning electron micrographs. The ability of polyphosphate to enhance fibrin clot turbidity was independent of factor XIIIa activity. When plasmin or a combination of plasminogen and tissue plasminogen activators were included in clotting reactions, fibrin clots formed in the presence of polyphosphate exhibited prolonged clot lysis times. Release of polyphosphate from activated platelets or infectious microorganisms may play an important role in modulating fibrin clot structure and increasing its resistance to fibrinolysis. Polyphosphate may also be useful in enhancing the structure of surgical fibrin sealants.
多聚磷酸盐是无机磷酸盐的线性聚合物，存在于血小板致密颗粒中，并在血小板激活时分泌。我们最近报道，多聚磷酸盐是一种有效的止血调节剂，可激活血液凝固的接触途径并加速因子V的激活。由于多聚磷酸盐不会改变凝血酶的凝血时间，它似乎在凝血酶上游发挥其所有促凝作用。我们现在报道，多聚磷酸盐以钙依赖的方式增强纤维蛋白凝块结构。在多聚磷酸盐存在下形成的纤维蛋白凝块浊度高达3倍，具有更高的质量-长度比，并且在扫描电子显微镜照片中显示出更粗的纤维。多聚磷酸盐增强纤维蛋白凝块浊度的能力与因子XIIIa活性无关。当在凝血反应中加入纤溶酶或纤溶酶原与组织纤溶酶原激活剂的组合时，在多聚磷酸盐存在下形成的纤维蛋白凝块表现出延长的凝块溶解时间。从活化的血小板或感染性微生物中释放多聚磷酸盐可能在调节纤维蛋白凝块结构和增加其对纤维蛋白溶解的抗性方面发挥重要作用。多聚磷酸盐也可能有助于增强手术纤维蛋白密封剂的结构。
