Plasma and cellular contributions to fibrin network formation, structure and stability.
Growing evidence suggests that fibrin network structure and stability are important determinants of haemostasis and thrombosis, with alterations in fibrin structure implicated as a causative mechanism in various haemostatic and thrombotic disorders. In haemophilia, for example, deficiency of factor VIII or IX reduces the rate and peak of thrombin generation and produces coarse fibrin clots that show increased susceptibility to fibrinolysis. More recently, studies have shown significant effects of cellular activity and integrin composition on fibrin network and stability. Platelets support the formation of a dense, stable fibrin network via interactions between the alphaIIbbeta3 integrin and the fibrin network, whereas tissue factor-bearing cells regulate fibrin structure and stability predominantly via procoagulant activity. Highly procoagulant extravascular cells (e.g. fibroblasts and smooth muscle cells) support the formation of dense fibrin networks that resist fibrinolysis, whereas unstimulated intravascular cells (e.g. endothelial cells) produce coarser networks that are susceptible to fibrinolysis. Moreover, cellular contributions produce heterogeneous clots in which fibrin network density and stability decrease with increasing distance from the cell surface. Together, these findings suggest that specific plasma and cellular mechanisms link thrombin generation, clot stability and haemostatic or thrombotic outcome. Understanding these mechanisms may provide new therapeutic targets in the management of bleeding and thrombotic disorders.
Wolberg
A S
AS
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599-7525, USA. alisa_wolberg@med.unc.edu
D001777:Blood Coagulation / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000502:physiology; D005337:Fibrin / Q000096:biosynthesis* / Q000737:chemistry; D005340:Fibrinogen / Q000096:biosynthesis / Q000737:chemistry; D005342:Fibrinolysis / Q000502:physiology; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D011994:Recombinant Proteins; D013917:Thrombin / Q000096:biosynthesis
D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin