impaired fibrin -chain cross-linking

We report a novel fibrinogen variant (fi-brinogen Seoul II), which has a heterozy-gous point mutation from CAA to CCA leading to AGln328Pro. The mutation site is among several glutamine residues that serve as-chain cross-linking accep-tor sites. Fibrinogen Seoul II was found in a 51-year-old male patient and his family in Seoul, Korea. The patient was diag-nosed with myocardial infarction at age 43. Eight years later he was admitted to the emergency room due to recurrence of the disease, where he expired under treat-ment with tissue plasminogen activator (t-PA). Fibrin polymerization curves, made using purified fibrinogen from the pa-tient’s relatives, showed a decreased fi-nal turbidity, suggesting Seoul II fibrin clots are composed of thinner fibers. This supposition was verified using scanning electron microscopy. Alpha-polymer for-mation by the mutant fibrinogen upon thrombin treatment in the presence of factor XIII and calcium was distinctly impaired. This result confirms that the residue A328 plays a pivotal role in -chain cross-linking. (Blood. 2006;108