Faculty Collaboration Database

The fibrinogen Aalpha R16C mutation results in fibrinolytic resistance. Br J Haematol 2006 Jul;134(2):220-6

Date

07/19/2006

Pubmed ID

16846481

DOI

10.1111/j.1365-2141.2006.06129.x

Scopus ID

2-s2.0-33745158288 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

The fibrinogen Aalpha R16C mutation is a common cause of dysfibrinogenaemia and has been previously associated with both bleeding and thrombosis. However, the mechanism underlying the thrombotic phenotype has not yet been elucidated. This report characterises the defect in fibrinolysis seen as a result of the Aalpha R16C mutation. A young patient with dysfibrinogenaemia (fibrinogen Hershey III) was found to be heterozygous for the Aalpha R16C mutation. Functional assays were performed on the purified fibrinogen to characterise clot formation and lysis with plasmin and trypsin. Consistent with previous results, clot formation was diminished. Unexpectedly, fibrinolysis was also delayed. Plasminogen activation was normal, ruling out decreased plasmin generation as the mechanism behind the fibrinolytic resistance. Western blot analysis showed no difference in the amount of bound alpha2-antiplasmin or albumin. When clot lysis was assayed with trypsin substituted for plasminogen, a significant delay was also observed, indicating that defective binding to plasminogen could not explain the fibrinolytic resistance. These results suggest that the defective fibrinolysis is due to increased proteolytic resistance, most likely reflecting changes in clot structure.

Author List

Flood VH, Al-Mondhiry HA, Farrell DH

Author

Veronica H. Flood MD Interim Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Child, Preschool
Coagulation Protein Disorders
Fibrin
Fibrinogen
Fibrinogens, Abnormal
Fibrinolysis
Heterozygote
Humans
Male
Mutation