The effect of platelets upon factor Xa-catalyzed activation of factor VII in vitro.
The authors have investigated the ability of platelets to enhance factor Xa-catalyzed activation of factor VII. Unstimulated platelets were without effect, whereas freeze/thawed platelets substantially enhanced activation. Antifactor V antibodies did not diminish the enhancement. Platelets activated by thrombin, collagen, or calcium ionophore A23187 also enhanced factor Xa-catalyzed activation of factor VII. In contrast to their lack of effect upon freeze/thawed platelets, antifactor V antibodies abolished augmented factor VII activation induced by activated platelets. Adding exogenous factor Va to unstimulated platelets failed to enhance factor Xa-catalyzed activation of factor VII, nor did adding exogenous factor Va to activated platelets augment activation beyond that observed with activated platelets alone. These observations can be interpreted as follows: (1) factor Va does not function as a cofactor for factor Xa-catalyzed activation of factor VII; (2) anionic phospholipids are a known cofactor for factor Xa-catalyzed activation of factor VII, and freeze/thawed platelets probably enhance activation by making anionic phospholipids on disrupted platelet membranes available to function as a cofactor; (3) the presumed binding of factor Xa to exogenous factor Va on unstimulated platelets is insufficient in itself to augment factor Xa-catalyzed activation of factor VII; (4) activated platelets augment factor Xa-catalyzed factor VII activation because activation allows both factor Xa to bind to released platelet factor V(a) and makes available a surface membrane component, probably anionic phospholipids, with which the bound factor Xa interacts.
D000990:Antithrombin III / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D005165:Factor V / Q000502:physiology; D005167:Factor VII / Q000378:metabolism*; D015943:Factor Va; D015951:Factor Xa; D006801:Humans; D066298:In Vitro Techniques; D010743:Phospholipids / Q000378:metabolism; D012697:Serine Endopeptidases / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology
D010743:Phospholipids; D000001:Calcimycin; D015943:Factor Va; D000990:Antithrombin III; D005165:Factor V; D005167:Factor VII; D012697:Serine Endopeptidases; D013917:Thrombin; D015951:Factor Xa