Abstract
Fibrinogen Caracas II is an abnormal fibrinogen involving the mutation of A alpha serine 434 to N-glycosylated asparagine. Some effects of this mutation on the ultrastructure of fibrinogen Caracas II molecules, fibers, and clots were investigated by electron microscopy. Electron microscopy of rotary shadowed individual molecules indicated that most of the alphaC domains of fibrinogen Caracas II do not interact with each other or with the central domain, in contrast to control fibrinogen. Negatively contrasted Caracas II fibers were thinner and less ordered than control fibers, and many free fiber ends were observed. Scanning electron microscopy of whole clots revealed the presence of large pores bounded by local fiber networks made up of thin fibers. Permeation experiments also indicated that the average pore diameter was larger than that of control clots. The viscoelastic properties of the Caracas II clot, as measured by a torsion pendulum, were similar to those of control clots. Both the normal stiffness and increased permeability of the Caracas II clots are consistent with the observation that subjects with this dysfibrinogenemia are asymptomatic.
Highlights
Fibrinogen Caracas II is an abnormal fibrinogen involving the mutation of A␣ serine 434 to N-glycosylated asparagine
Some effects of this mutation on the ultrastructure of fibrinogen Caracas II molecules, fibers, and clots were investigated by electron microscopy
Lateral aggregation of protofibrils eventually yield fibrin fibers that have a characteristic pattern of striations with a periodicity of 22.5 nm as observed by electron microscopy
Summary
Fibrinogen Caracas II is an abnormal fibrinogen involving the mutation of A␣ serine 434 to N-glycosylated asparagine. Purified fragment X2 monomer, which consists of fibrin monomer lacking both of the ␣C domains, exhibits a decreased rate of lateral aggregation when compared with fibrin monomer containing both ␣C domains [2] These results indicated that the ␣C domains accelerate the polymerization of fibrin and influence the final structure of the clot, they are not essential for either branching or lateral aggregation. When the ␣C domains are blocked by ␣C fragments [1, 7] or monoclonal antibodies specific for for the ␣C domain [8], both the rate and extent of lateral aggregation are decreased The latter effect, which results in thinner fibers, suggests that modification of the ␣C domains, as opposed to their removal, may have an additional inhibitory effect on fibrin polymerization
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