A severe hereditary bleeding disorder was described in a large family from east Texas in 2001.
The affected family members routinely had bruising, nosebleeds, massive blood loss following injury or surgery, and often required blood transfusions. Routine tests for functional components of the blood coagulation pathway did not reveal any obvious defects.
Genomic sequencing revealed a mutation in the gene encoding coagulation factor 5 (FV), but it was not considered to contribute to disease, since clotting assays were normal.
In the Journal of Clinical Investigation, Björn Dahlbäck and colleagues at Lund University reveal that this mutation results in a truncated form of FV. This truncated FV was present in plasma from all affected family members.
The authors demonstrate that truncated FV forms a complex with tissue factor pathway inhibitor-α (TFPI) that inhibits coagulation pathways.
In an accompanying commentary, George Brooze and Thomas Girard at Washington University suggest that treatment of family members with the Texas bleeding disorder with TFPI inhibitors may relieve symptoms of the disorder.
Article: Coagulation factor VA2440G causes east Texas bleeding disorder via TFPIα