Genetics and Genomics in the Management of Hemostasis and Thrombosis
Blood coagulation is a cell surface biochemical event designed to stem the loss of blood following vascular injury and provide the necessary molecular, cellular, and protein constituents for growth and repair. In addition, coagulation occurring within medium-sized arteries and veins can have detrimental effects, ranging from end-organ damage to death. Conceptually, blood coagulation represents a complex, yet well coordinated, series of events that involve tissue factor-bearing cells and platelets. The initiation and propagation phases of coagulation under biological conditions are catalyzed by thrombin in small (nM) and large concentrations. Fibrin is the predominant protein constituent of blood clots formed from fibrinogen, a large glycoprotein present within the circulation. Fibrin clot architecture plays an important role in hemostasis and vascular repair, and variations have important clinical implications. In turn, variability in fibrin strand width, branch points, mass-to-length ratio, density, and cross-linking among healthy individuals, as well as those with atherosclerosis, metabolic disorders, and other prothrombotic disease states, support both genetic and environmental influences. Alterations in gene expression and coding function, splice variants, and posttranslational modifications influence fibrin structure and functionality. © 2010 Copyright © 2010 Elsevier Inc. All rights reserved.
