Regulation of Factor Xla Activity by Platelets and a 1 - Protease Inhibitor

We have studied the complex interrelationships between platelets, Factor XIa, a1-protease inhibitor and Factor IX activation. Platelets were shown to secrete an inhibitor of Factor XMa, and to protect Factor XIa from inactivation in the presence of a1-protease inhibitor and the secreted platelet inhibitor. This protection of Factor Ma did not arise from the binding of Factor XIa to platelets, the presence of high molecular weight kininogen, or the inactivation of a1-protease inhibitor by platelets. The formation of a complex between a1-protease inhibitor and the active-site-containing light chain of Factor XMa was inhibited by activated platelets and by platelet releasates, but not by high molecular weight kininogen. These results support the hypothesis that platelets can regulate Factor XIa-catalyzed Factor IX activation by secreting an inhibitor of Factor XIa that may act primarily outside the platelet microenvironment and by protecting Factor XIa from inhibition, thereby localizing Factor IX activation to the platelet plug.