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Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
Published on: September 9, 2012
Coexisting dysfibrinogenemia (gammaR275C) and factor V Leiden deficiency associated with thromboembolic disease
K R Siebenlist1, M W Mosesson, D A Meh
1Department of Biomedical Sciences, College of Health Sciences, Marquette University, Milwaukee, Wisconsin, USA. siebenlistk@vms.csd.mu.edu
Abstract:
Fibrinogen Cedar Rapids is a heterozygous dysfibrinogenemia (gammaR275C) that was associated with thromboembolism during and following pregnancy in three second-generation family members who also were heterozygotic for factor V Leiden (V R506Q). Like other dysfibrinogenemias with substitutions at position 275 of the gamma-chain, fibrinogen Cedar Rapids is characterized by defective end-to-end intermolecular fibrinogen and fibrin 'D : D' associations, a fibrin network structure that is composed of thicker and more highly branched fibers, normal fibrin 'D: E' associations, and normal factor XIII-mediated crosslinking of fibrinogen and fibrin. In addition, Cedar Rapids fibrinogen and fibrin displayed delayed plasmin lysis rates. Compared with normal fibrinogen, platelet aggregation or platelet fibrinogen receptor clustering was defective in the presence of fibrinogen Cedar Rapids. Most subjects with gammaR275 mutations do not experience clinical thrombotic disorders, suggesting that the combination of a factor V Leiden defect and a gammaR275C dysfibrinogenemia predisposes to thromboembolic disease.
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