The effects of additional carbohydrate in the coiled‐coil region of fibrinogen on polymerization and clot structure and properties: characterization of the homozygous and heterozygous forms of fibrinogen Lima (Aα Arg141→Ser with extra glycosylation)

Summary.  Fibrinogen Lima is an abnormal fibrinogen with an Aα Arg141→Ser substitution resulting in an extra N‐glycosylation at Aα Asn139, which seems to be responsible for the impairment of fibrin polymerization. We have studied the polymerization and properties of clots made from both plasma and purified fibrinogen of both the homozygous and heterozygous forms. The clot permeation studies with both plasma and purified protein revealed a normal flux through the network for the heterozygous form but very decreased permeation in the homozygous form. Consistent with turbidity results, the clot network of the homozygous form, seen by scanning electron microscopy, was tight and composed of thin fibers, with many branch points, while the appearance of clots from the heterozygous form was similar to that of control clots, but in both cases the fibers were more curved than those of control clots. The rheological properties of clots from the homozygous form were also altered, with rigidity being increased in plasma clots, but decreased in the purified system, a consequence of the balance between numbers of branch points and fiber curvature. From these results it seems that the extra carbohydrate moiety, located in the α coiled‐coil region close to the βC domains, impairs the protofibril lateral association process, giving rise to thinner, more curved fibers, with the structural anomalies being most pronounced in the clots from the homozygous plasma. These studies support a model for fibrin polymerization in which the βC–βC interactions are involved in lateral aggregation.