The relationship between factor VII coagulant activity and factor XII activation induced in plasma by endogenous or exogenously added contact surface.
The contribution of various enzymes in the activation of factor VII, determined from the increase in factor VII coagulant activity (VIIc), was investigated following the exposure of citrated plasma to low temperature. The contact system of coagulation was initiated either by the contact surface present in certain plasmas (i.e. plasma from women in late pregnancy) or by micellar stearate added to plasma diluted with an equal volume of buffer (plasma from normal healthy subjects or from women in late pregnancy). With either of the contact surfaces, increase of VIIc and the concentration of enzymes derived from factor XII (XIIa) depended on the potency of the contact surface. The stearate-induced VIIc in diluted plasmas from women in late pregnancy or from normal subjects was inhibited by 60-70% in the presence of anti-factor IX monoclonal antibody. VIIc was not increased in XII-deficient plasma following the addition of stearate. The addition of purified human factor XII to this plasma restored the increase in VIIc and the activation of factor XII. In factor IX-deficient plasma, the stearate-induced increase in VIIc was only 38% of that seen in normal plasma and was restored by the addition of purified factor IX. Similarly in factor XI-deficient plasma, the stearate-induced increase in VIIc and the factor XII activation were 48% and 69% of that found in normal plasma. The addition of EDTA (2 mM) did not alter the extent of factor XII activation induced by contact surface, but it did inhibit the rise in VIIc. It is concluded that in the presence of contact surface the activation of factor XII and the sequential activation of factor XI and of factor IX results in the activation of factor VII. Activated factor IX is responsible for the major part of the factor VII activation whereas the rest may be through the direct activation by XIIa.
MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, Medical College of St Bartholomew's Hospital, London, UK.
K A
KA
Mitropoulos
B E
BE
Reeves
D P
DP
O'Brien
J A
JA
Cooper
J C
JC
Martin
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001777:Blood Coagulation; D004789:Enzyme Activation; D005164:Factor IX / Q000737:chemistry / Q000502:physiology*; D005167:Factor VII / Q000502:physiology*; D005174:Factor XII / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D005260:Female; D006801:Humans; D011247:Pregnancy; D013499:Surface Properties
D000911:Antibodies, Monoclonal; D005167:Factor VII; D005164:Factor IX; D005174:Factor XII