Fibrinogen Caracas V is a thrombotic dysfibrinogenemia with an Aalpha 532 Ser-->Cys mutation characterized by a tight
fibrin network formed of thin fibers responsible for a less porous clot than a normal one. In the present work,
fibrinogen Caracas V is further characterized in order to understand the relationship between the structural defect and
thrombophilia. This thrombotic disorder has been attributed to a tight
fibrin network responsible for a decreased permeation of flow through the clot, leading to defective
thrombus lysis due to a diminished availability of fibrinolytic
enzymes to the inner
fibrin surface. Correction of clot structure anomaly, by addition of
dextran 40 to
fibrinogen before clotting, induces an improvement in
fibrin degradation that was attributed to an increase in porosity. The
pulmonary embolism observed in this family has been related to an hyper rigidity of the clot, an anomaly that is also corrected by
dextran. Furthermore, this abnormal
fibrinogen binds more
albumin than does normal
fibrinogen, a phenomenon attributed to the mutation of
serine in Aalpha-532 by
cysteine. Therefore, this
fibrinogen shows a striking similarity to the
fibrinogen Dusart, allowing us to confirm that the alphaC-terminal part of
fibrinogen plays an important role in
fibrin structure, and to conclude that the anomaly of
fibrin network observed in
fibrinogen Caracas V is responsible for a deficient
thrombus lysis.