Factor XII-independent activation of factor XI in plasma: effects of sulfatides on tissue factor-induced coagulation.
Factor XI (FXI) may be activated in a purified system by thrombin and by autoactivation in the presence of negatively charged substances such as dextran sulfate or sulfatides. The current studies were performed to determine if these processes occur during the coagulation of plasma. FXII--deficient plasma was supplemented with 125I-FXI and clot formation was induced with tissue factor and/or sulfatides. Cleavage of FXI was studied by standard polyacrylamide gel electrophoresis and autoradiography. Activated FXI (FXIa) was detected after 20 minutes of incubation with sulfatides alone and this process was markedly accelerated by the addition of tissue factor (TF). The enhancing effect of TF was blocked by hirudin, which indicated thrombin involvement in FXI activation. The contribution of FXIa to FIX activation in this system was studied using a 3H-FIX activation peptide release assay. Sulfatides increased FIX activation about twofold in plasma induced to clot with TF but had no effect if the plasma was immunodepleted of FXI. FIX activation was also increased in plasma induced to clot with FXa if sulfatides were present. The enhanced generation of FIXa was dependent on FXI and was blocked by hirudin. Some activation was seen in the reactions with sulfatides and hirudin and is likely solely caused by FXI autoactivation. The data indicate that during the coagulation of plasma in the presence of sulfatides, FXI is activated by a mechanism that is thrombin dependent and does not require FXII.
Gailani
D
D
Division of Hematology Research, Jewish Hospital, Washington University, St Louis, MO 63110.
Broze
G J
GJ
D001777:Blood Coagulation; D004789:Enzyme Activation; D005172:Factor XI / Q000378:metabolism*; D005174:Factor XII / Q000378:metabolism*; D015951:Factor Xa / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007704:Kininogens / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
D007704:Kininogens; D013433:Sulfoglycosphingolipids; D005174:Factor XII; D005172:Factor XI; D013925:Thromboplastin; D013917:Thrombin; D015951:Factor Xa