Abstract
A kinetic analysis was developed to determine the steady state kinetic parameter Kcat/KM for the thrombin-catalyzed release of FPA from abnormal and normal fibrinogen in mixtures of the two. Such mixtures are likely to comprise the fibrinogen of individuals with congenital dysfibrinogenemia. The analysis was used to characterize fibrinogen Grand Rapids a new congenital dysfibrinogenemia. It indicated that fibrinogen from affected individuals was composed of normal and abnormal fibrinogen in roughly equal amounts, and that the value of kcat/KM for the thrombin-catalyzed release of FPA from the fibrinogen variant was 77-fold lower than that for the release of FPA from the normal fibrinogen. In separate studies, fibrinogen Grand Rapids was found to exhibit a reduced clottability. Additionally, affected individuals appeared to have plasma fibrinogen concentrations which were about one-third the normal value.
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