Human factor Va1 and factor Va2: properties in the procoagulant and anticoagulant pathways.
Human plasma factor V is heterogeneous and yields two forms of activated factor V that bind with low (factor Va1) and high affinity (factor Va2) to phospholipids. The properties of factor Va1 and factor Va2 in the anticoagulant and procoagulant pathways were evaluated by comparing their sensitivity for inactivation by APC and their ability to act as cofactor in prothrombin activation. At low phospholipid concentrations and on membranes containing low amounts of phosphatidylserine (PS), factor Va1 was inactivated by APC at 15-fold lower rates than factor Va2, both in the absence and in the presence of protein S. At high phospholipid concentrations and on membranes with more than 15 mol % PS, factor Va1 and factor Va2 were inactivated with equal efficiency. Differences between cofactor activities of factor Va1 and factor Va2 in prothrombin activation were only observed on membranes with less than 7.5 mol % PS. Due to the different phospholipid requirements of APC-catalyzed factor Va inactivation and of expression of factor Va cofactor activity in prothrombin activation, the thrombin-forming capacity of factor V1 was 7-fold higher than that of factor V2 in a reaction system containing factor Xa, prothrombin, APC, protein S, vesicles with a phospholipid composition resembling that of activated platelets, and traces of thrombin to initiate prothrombin activation. This shows that in the process of generation, expression, and down-regulation of factor Va cofactor activity on physiological membranes, the overall procoagulant activity of factor V1 can considerably exceed that of factor V2.
Hoekema
L
L
Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Nicolaes
G A
GA
Hemker
H C
HC
Tans
G
G
Rosing
J
J
D001777:Blood Coagulation; D015943:Factor Va / Q000302:isolation & purification / Q000378:metabolism*; D015951:Factor Xa / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010718:Phosphatidylserines / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology; D011486:Protein C / Q000378:metabolism*; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D010718:Phosphatidylserines; D010743:Phospholipids; D011486:Protein C; D015943:Factor Va; D011516:Prothrombin; D013917:Thrombin; D015951:Factor Xa