title: A comparison of phospholipid and platelets in the activation of human factor VIII by thrombin and factor Xa, and in the activation of factor X.
abstract: Two aspects of the activation of factor X by the intrinsic clotting pathway have been studied in purified human systems, in the presence of either purified phosphatidylserine:phosphatidylcholine vesicles (PS:PC) or platelets activated with ionophore A23187: (1) the activation of factor VIII by factor Xa and by thrombin, and (2) the activation of factor X by the factor IXa/VIIIa complex. Factor VIII activation by thrombin was unaffected in either rate or extent by the presence of PS:PC or activated platelets. In contrast, factor VIII activation by factor Xa required either PS:PC or platelets. The products of optimal factor VIII activation by the two enzymes, designated factor VIIIa(T) and factor VIIIa(Xa), are kinetically different in the activation of factor X by factor IXa, factor VIIIa(T) being approximately twice as active (in factor X activation) as factor VIIIa(Xa) in the presence of PS:PC or platelets. Factor VIIIa(Xa) can be converted to the more active VIIIa(T) by thrombin treatment, but the activity of factor VIIIa(T) is unchanged by factor Xa treatment. Factor X activation was also studied with optimally activated factor VIIIa(T), in the presence of PS:PC or activated platelets, as a function of factor IXa concentration in order to determine the apparent dissociation constant for the factor IXa-VIIIa interaction in the two cases. Activated platelets increased the apparent affinity more than fivefold.
mesh_terms: D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology*; D005169:Factor VIII / Q000378:metabolism*; D005170:Factor X / Q000378:metabolism*; D015951:Factor Xa; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010713:Phosphatidylcholines / Q000502:physiology; D010718:Phosphatidylserines / Q000502:physiology; D010743:Phospholipids / Q000502:physiology*; D012697:Serine Endopeptidases / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*
chemical_list: D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D010743:Phospholipids; D005169:Factor VIII; D005170:Factor X; D012697:Serine Endopeptidases; D013917:Thrombin; D015951:Factor Xa