Blood coagulation factor IX is activated during hemostasis by two distinct
mechanisms. Activation through factor VIIa/tissue factor occurs early in th
e course of fibrin clot formation. Activation by factor XIa appears to be i
mportant for maintaining the integrity of the clot over time. In general co
agulation proteases are activated on a phospholipid surface in the presence
of a protein cofactor Until recently, activation of factor IX by factor XI
a was thought to be the exception to this rule, as phospholipid has no effe
ct on the reaction and no cofactor had been identified. These curious obser
vations suggest that factor IX is activated by factor XIa in the fluid phas
e. A large amount of Mew evidence now indicates that factor IX activation b
y factor XIa occurs on the surface of activated platelets. The data suggest
, however, that this reaction differs significantly from. other protease-su
bstrate interactions on the platelet surface. This is likely to be due, in
part, to the unusual structure of the factor XI molecule. (C) 2001, Elsevie
r Science Inc. All rights reserved.