Contact Activation of Factor XI

S ummary . Factor XI is a circulating trace plasma protein composed of two similar or identical chains of about 80 000 daltons which upon activation undergo proteolytic cleavage. Recently, we have shown that trypsin activation leads to an active factor XI (factor XI_a) which, on reduction, yields three chains of 46 000, 37 000 and 26 000 daltons. Herein, we re-evaluate the effect of contact activation of factor XI at an activating surface both in normal human plasma and in a mixture of purified factors XI, XII, and high molecular weight kininogen (HMWK). Mixtures were analysed by coagulant activity and by reduced sodium dodecyl sulphate 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. In contrast, 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. We propose that factor XI_a containing only 46 000 and 37 000 chains be designated factor XI_aα, and that factor XI_a containing the third chain of 23 000 daltons be designated factor XI_aβ. Sequential elution of contact activated plasma factor XI revealed that factor XI_a was attached to the glass surface through the 46 000 dalton chain.