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The role of activated human platelets in prothrombin and factor X
activation
J Rosing, JL van Rijn, EM Bevers, G van Dieijen, P Comfurius and RF Zwaal
The effect of activated human platelets in intrinsic factor X activation
was compared with their effect in prothrombin activation. Compared with
unstimulated platelets, platelets triggered by the combined action of
collagen plus thrombin showed a tenfold activity increase in prothrombin
activation, and a 20-fold rate enhancement in factor X activation.
Treatment of collagen plus thrombin-stimulated platelets with N.naja
phospholipase A2 almost completely abolished their activity in prothrombin
and factor X activation. Since no significant cell lysis occurs during
phospholipase treatment, this indicates that platelet phospholipids,
exposed at the membrane exterior, play an essential role in the interaction
of platelets with the proteins of the prothrombin and factor X-activating
complexes. The time course of generation of the procoagulant platelet
surface was different when the amount of coagulation factors present in the
assay systems was varied. At suboptimal concentrations of coagulation
factors, maximum platelet activity was reached after a shorter time period
than at saturating concentrations. When measured at suboptimal amounts of
coagulation factors, the platelet activity in prothrombin and factor X
activation is also more sensitive to phospholipase treatment. Experiments
with synthetic phospholipid mixtures show that prothrombin and factor X
activation are optimal at low mol% phosphatidylserine when high
concentrations of factor Va and factor VIIIa are employed. The optimal mol%
phosphatidylserine increases when the concentrations of nonenzymatic
protein cofactors are lowered. These findings are discussed in relation to
a model in which phosphatidylserine, exposed at the outer surface of
activated platelets, plays an essential role in prothrombin and factor X
activation. It is proposed that this phosphatidylserine is not
homogeneously distributed in the platelet outer membrane, but that areas
with different phosphatidylserine density participate in coagulation factor
activation.
Volume 65,
Issue 2,
pp. 319-332,
02/01/1985
Copyright © 1985 by The American Society of Hematology
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