Coexisting dysfibrinogenemia (γR275C) and factor V leiden deficiency associated with thromboembolic disease (fibrinogen Cedar Rapids)

Fibrinogen Cedar Rapids is a heterozygous dysfibrinogenemia (γR275C) that was associated with thromboembolism during and following pregnancy in three second-generation family members who also were heterozygotic for factor V Leiden (V R506Q). Like other dysfibrinogenemias with substitutions at position 275 of the γ-chain, fibrinogen Cedar Rapids is characterized by defective end-to-end intermolecular fibrinogen and fibrin 'D: D' associations, a fibrin network structure that is composed of thicker and more highly branched fibers, normal fibrin 'D : E' associations, and normal factor XIII-mediated crosslinking of fibrinogen and fibrin. In addition, Cedar Rapids fibrinogen and fibrin displayed delayed plasmin lysis rates. Compared with normal fibrinogen, platelet aggregation or platelet fibrinogen receptor clustering was defective in the presence of fibrinogen Cedar Rapids. Most subjects with γR275 mutations do not experience clinical thrombotic disorders, suggesting that the combination of a factor V Leiden defect and a γR275C dysfibrinogenemia predisposes to thromboembolic disease. (C) 2000 Lippincott Williams and Wilkins.