Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation.
A study was carried out on mechanisms, independent of activated Factor XI, capable of activating Factor IX. The reaction product of tissue factor and Factor VII functioned as a potent Factor IX activator in the assay system used. Activated Factor IX itself activated Factor X; thrombin failed to activate Factor IX. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis confirmed that the reaction product of tissue factor and Factor VII activated Factor IX, with replacement of the band corresponding to native factor IX [molecular weight (Mr) 55,000] by bands corresponding to the heavy chain (Mr 27,000) and light chain (Mr 17,000) of activated Factor IX. When either Factor VII or calcium ions were left out of incubation mixtures, the band of native Factor IX persisted unchanged. Contact of blood with tissue factor represents a second mechanism, bypassing activated Factor XI, for the activation of Factor IX during hemostasis. It may help to explain the discrepancy between the mild bleeding of hereditary Factor XI deficiency and the severe bleeding of hereditary Factor IX deficiency.
D000818:Animals; D001777:Blood Coagulation; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D005164:Factor IX / Q000378:metabolism*; D005167:Factor VII / Q000378:metabolism*; D005172:Factor XI / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010714:Phosphatidylethanolamines / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
D010714:Phosphatidylethanolamines; D005167:Factor VII; D005164:Factor IX; D005172:Factor XI; D013925:Thromboplastin; D002118:Calcium
Blood. 1963 Feb;21:221-36
13973081
Nature. 1954 Nov 6;174(4436):880-1
13214029
J Biol Chem. 1951 Nov;193(1):265-75
14907713
Blood. 1977 Sep;50(3):351-66
884315
Blood. 1977 May;49(5):819-34
851644
Thromb Res. 1975 Sep;7(3):373-82
1188839
Thromb Diath Haemorrh. 1972 Oct 31;28(2):317-24
4629507
Biochemistry. 1974 Oct 22;13(22):4508-16
4473201
Biochemistry. 1973 Nov 20;12(24):4938-45
4796921
Biochemistry. 1972 Jul 18;11(15):2853-7
5041901
Biochem J. 1975 Mar;145(3):469-74
1171684
FEBS Lett. 1975 Feb 15;50(3):382-5
1116608
Biochim Biophys Acta. 1971 Oct;250(1):210-5
5168884
Biochemistry. 1969 Apr;8(4):1397-405
5817155
Scand J Haematol. 1966;3(1):59-75
5914457
Thromb Diath Haemorrh Suppl. 1965;17:35-44
5874847