The fibrinogen Aα R16C mutation results in fibrinolytic resistance

Veronica H. Flood, Hamid A. Al-Mondhiry, David H. Farrell

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The fibrinogen Aα 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 Aα R16C mutation. A young patient with dysfibrinogenaemia (fibrinogen Hershey III) was found to be heterozygous for the Aα 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 α2-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.

Original languageEnglish (US)
Pages (from-to)220-226
Number of pages7
JournalBritish Journal of Haematology
Volume134
Issue number2
DOIs
StatePublished - Jul 1 2006

Fingerprint

Plasminogen
Fibrinolysis
Fibrinogen
Fibrinolysin
Trypsin
Mutation
Antifibrinolytic Agents
Albumins
Thrombosis
Western Blotting
Hemorrhage
Phenotype

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Flood, Veronica H. ; Al-Mondhiry, Hamid A. ; Farrell, David H. / The fibrinogen Aα R16C mutation results in fibrinolytic resistance. In: British Journal of Haematology. 2006 ; Vol. 134, No. 2. pp. 220-226.
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The fibrinogen Aα R16C mutation results in fibrinolytic resistance. / Flood, Veronica H.; Al-Mondhiry, Hamid A.; Farrell, David H.

In: British Journal of Haematology, Vol. 134, No. 2, 01.07.2006, p. 220-226.

Research output: Contribution to journalArticle

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