Kr. Siebenlist et al., Coexisting dysfibrinogenemia (gamma R275C) and factor V Leiden deficiency associated with thromboembolic disease (fibrinogen Cedar Rapids), BL COAG FIB, 11(3), 2000, pp. 293-304
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.