Thrombotic dysfibrinogenemia: Fibrinogen "Caracas V" relation between verytight fibrin network and defective clot degradability

Fibrinogen Caracas V is a thrombotic dysfibrinogenemia with an A alpha 532 Ser-->Cps mutation characterized by a tight fibrin network formed of thin f ibers 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 thro mbotic disorder has been attributed to a tight fibrin network responsible f or a decreased permeation of flow through the clot, leading to defective th rombus lysis due to a diminished availability of fibrinolytic enzymes to th e inner fibrin surface. Correction of clot structure anomaly, by addition o f dextran 40 to fibrinogen before clotting, induces an improvement in fibri n 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 a bnormal fibrinogen binds more albumin than does normal fibrinogen, a phenom enon attributed to the mutation of serine in A alpha-532 by cysteine. There fore, this fibrinogen shows a striking similarity to the fibrinogen Dusart, allowing us to confirm that the alpha C-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 defici ent thrombus lysis. (C) 2000 Elsevier Science Ltd. All rights reserved.