Contact Activation of Factor XI

Abstract
Factor XI is a circulating trace plasma protein composed of 2 similar or identical chains of about 80,000 daltons which upon activation undergo proteolytic cleavage. Trypsin activation was previously shown to lead to an active factor XI (factor XIa) which, on reduction, yields 3 chains of 46,000, 37,000 and 26,000 daltons. The effect of contact activation of factor XI at an activating surface was re-evaluated in normal human plasma and in a mixture of purified factors XI, XII and high MW kininogen (HMWK). Mixtures were analyzed by coagulant activity and by reduced sodium dodecyl sulfate polyacrylamide gel electrophoresis using [125I]factor XI. In the purified system, fully activated factor XI on reduction yielded chains of 46,000, 37,000 and 23,000 daltons. Factor XI activated by surface contact in plasma yielded on reduction only chains of 46,000 and 37,000 daltons in addition to some uncleaved 80,000 chain. Factor XIa containing only 46,000 and 37,000 chains should be designated factor XIa.alpha.; factor XIa containing the 3rd chain of 23,000 daltons should be designated factor XIa.beta.. Sequential elution of contact activated plasma factor XI revealed that factor XIa was attached to the glass surface through the 46,000 dalton chain.