Coexisting dysfibrinogenemia (gamma R275C) and factor V Leiden deficiency associated with thromboembolic disease (fibrinogen Cedar Rapids)

Fibrinogen Cedar Rapids is a heterozygous dysfibrinogenemia (gamma R275C) t hat was associated with thromboembolism during and following pregnancy in t hree second-generation family members who also were heterozygotic for facto r V Leiden (V R506Q). Like other dysfibrinogenemias with substitutions at p osition 275 of the gamma-chain, fibrinogen Cedar Rapids is characterized by defective end-to-end intermolecular fibrinogen and fibrin 'D : D' associat ions, a fibrin network structure that is composed of thicker and more highl y branched fibers, normal fibrin 'D : E' associations, and normal factor XI II-mediated crosslinking of fibrinogen and fibrin. In addition, Cedar Rapid s fibrinogen and fibrin displayed delayed plasmin lysis rates. Compared wit h normal fibrinogen, platelet aggregation or platelet fibrinogen receptor c lustering was defective in the presence of fibrinogen Cedar Rapids. Most su bjects with gamma R275 mutations do not experience clinical thrombotic diso rders, suggesting that the combination of a factor V Leiden defect and a ga mma R275C dysfibrinogenemia predisposes to thromboembolic disease. Blood Co agul Fibrinolysis 11:293-304 (C) 2000 Lippincott Williams & Wilkins.