Published online before print December 1, 2003, doi: 10.1161/01.ATV.0000109748.77727.3e
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© 2004 American Heart Association, Inc.
Thrombosis |
Influence of 
' Fibrinogen Splice Variant on Fibrin Physical Properties and Fibrinolysis Rate
From the Department of Cardiology (J.P.C., G.M.), Pitié-Salpêtrière Hospital, Paris, France (AP-HP); Department of Cell and Developmental Biology (J.P.C., C.N., J.W.W.), University of Pennsylvania School of Medicine, Philadelphia, PA; and Department of Pathology (D.H.F.), Oregon Health & Sciences University, Portland, OR.
Correspondence to J. W. Weisel, Department of Cell and Developmental Biology, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104. E-mail weisel{at}mail.cellbio.upenn.edu
Objective— A splice variant of fibrinogen, 
', has an altered C-terminal sequence in its gamma chain. This A/' fibrin is more resistant to lysis than A/A fibrin. Whether the physical properties of ' and A fibrin may account for the difference in their fibrinolysis rate remains to be established.
Methods and Results— Mechanical and morphological properties of cross-linked purified fibrin, including permeability (Ks, in cm2) and clot stiffness (G', in dyne/cm2), were measured after clotting A and ' fibrinogens (1 mg/mL). '/' fibrin displayed a non-significant decrease in the density of fibrin fibers and slightly thicker fibers than A/A fibrin (12±2 fiber/10-3nm3 versus 16±2 fiber/10-3nm3 and 274±38 nm versus 257±41 nm for '/' and A/A fibrin, respectively; P=NS). This resulted in a 20% increase of the permeability constant (6.9±1.7 10-9 cm2 versus 5.5±1.9 10-9 cm2, respectively; P=NS). Unexpectedly, ' fibrin was found to be 3-times stiffer than A fibrin (72.6±2.6 dyne/cm2 versus 25.1±2.3 dyne/cm2; P<0.001). Finally, there was a 10-fold decrease of the fibrin fiber lysis rate.
Conclusions— Fibrinolysis resistance that arises from the presence of A/' fibrinogen in the clot is related primarily to an increase of fibrin cross-linking with only slight modifications of the clot architecture.
Key Words: coagulation • fibrin • fibrinogen • fibrinolysis • thrombosis
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