Contact activation of factor XI

Area of Science:

• Biochemistry
• Hematology
• Molecular Biology

Background:

• Factor XI is a plasma protein crucial for blood coagulation.
• Activation of Factor XI (FXI) leads to Factor XIa (FXIa), a key enzyme in the intrinsic pathway.
• Previous studies showed trypsin activation yields FXIa with three chains (46, 37, 26 kDa).

Purpose of the Study:

• To investigate the distinct activation products of Factor XI under different conditions.
• To differentiate between trypsin-activated FXI and surface-contact-activated FXI.
• To characterize the molecular forms of FXI generated during contact activation in plasma.

Main Methods:

• Analysis of Factor XI activation using coagulant activity assays.
• Reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with radiolabeled [125I]Factor XI.
• Comparison of Factor XI activation in purified systems versus normal human plasma.

Main Results:

• Contact activation in purified systems yielded FXIa with 46, 37, and 23 kDa chains.
• Contact activation in plasma produced FXIa with only 46 and 37 kDa chains, alongside uncleaved FXI.
• Two distinct forms were proposed: FXIa alpha (46/37 kDa) and FXIa beta (46/37/23 kDa).
• FXIa alpha was found to bind to activating surfaces via the 46 kDa chain.

Conclusions:

• Factor XI activation pathways generate distinct molecular species.
• Surface contact activation in plasma primarily produces FXIa alpha.
• The 46 kDa chain of FXIa alpha mediates its attachment to activating surfaces.