Elucidating the role of carbohydrate determinants in regulating hemostasis: insights and opportunities

Recent improvement in modern analytical technologies has stimulated an explosive growth in the study of glycobiology. In turn, this has lead to a richer understanding of the crucial role of N- and O-linked carbohydrates in dictating the properties of the proteins to which they are attached and, in particular, their centrality in the control of protein synthesis, longevity, and activity. Given their importance, it is unsurprising that both gross and subtle defects in glycosylation often contribute to human disease pathology. In this review, we discuss the accumulating evidence for the significance of glycosylation in mediating the functions of the plasma glycoproteins involved in hemostasis and thrombosis. In particular, the role of naturally occurring coagulation protein glycoforms and inherited defects in carbohydrate attachment in modulating coagulation is considered. Finally, we describe the therapeutic opportunities presented by new insights into the role of attached carbohydrates in shaping coagulation protein function and the promise of carbohydrate modification in the delivery of novel therapeutic biologics with enhanced functional properties for the treatment of hemostatic disorders.