Evidence against collagen activation of platelet-associated factor XI as a mechanism for initiating intrinsic clotting.
Collagen activation of platelet-associated Factor XI has been proposed as a mechanism for initiating intrinsic clotting independent of Factor XII. Since this could explain the lack of bleeding in patients with hereditary Factor XII deficiency, prekallikrein deficiency and high molecular weight kininogen deficiency, we subjected the hypothesis to rigorous testing. Incubation of isolated platelets with collagen and calcium ions failed to generate activity shortening the clotting time of an activated Factor XI (XIa) assay that had been modified to eliminate effects due to platelet-associated activated Factor V. Nor could generation of traces of Factor XIa in such mixtures be detected by incubation with purified Factor IX and testing for the generation of activated Factor IX (IXa) in clotting and amidolytic assays. Moreover, when blood or platelet-rich plasma containing added 125I-Factor IX was incubated with calcium ions and collagen and then subjected to reduced sodium dodecyl sulfate polyacrylamide gel electrophoresis, the radioactivity profiles revealed only native 125I-Factor IX without evidence of the polypeptide chains of Factor IXa. The negative results of this study mitigate against the hypothesis that collagen activation of platelet-associated Factor XI represents a physiologically significant mechanism for initiating clotting independent of Factor XII.
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005164:Factor IX / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D005172:Factor XI / Q000378:metabolism*; D006801:Humans; D010743:Phospholipids / Q000097:blood
D010743:Phospholipids; D005169:Factor VIII; D005164:Factor IX; D005170:Factor X; D003094:Collagen; D005172:Factor XI; D002118:Calcium