Development of procoagulant binding sites on the platelet surface.
Activation of coagulation factor X by a complex of factors IXa-VIIIa and prothrombin by a complex of factor Xa.Va is markedly enhanced in the presence of a negatively-charged phospholipid surface. A suitable phospholipid surface is provided by a platelet lysate but not by a suspension of intact platelets, due to the internal localization of phosphatidylserine in the platelet membrane. Upon stimulation of platelets with a combination of collagen and thrombin, or calcium ionophore A23187 or treatment with diamide, alterations in the distribution of membrane phospholipids take place resulting in the exposure of significant amounts of phosphatidylserine at the platelet surface. As a consequence, an increased number of intrinsic factor X and prothrombinase complexes can be assembled at the platelet surface thus leading to an acceleration of factor Xa and thrombin formation. Studies with pathological platelets have shown that neither release nor aggregation are essential to provoke prothrombinase activity. The relatively high prothrombinase activity of non-stimulated Bernard-Soulier platelets is in agreement with the slightly altered phospholipid distribution in these platelets, in which more phosphatidylserine is exposed at the outer surface. Disturbances in the membrane bilayer structure as well as changes in the plasma membrane-cytoskeleton interaction are considered as possible explanations for the increased transbilayer movement of phosphatidylserine.
D001606:Bernard-Soulier Syndrome / Q000201:enzymology; D001665:Binding Sites; D001777:Blood Coagulation; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D005165:Factor V / Q000502:physiology; D005170:Factor X / Q000502:physiology; D006801:Humans; D008563:Membrane Lipids / Q000097:blood; D010741:Phospholipases A / Q000494:pharmacology; D010743:Phospholipids / Q000097:blood; D010981:Platelet Storage Pool Deficiency / Q000201:enzymology; D011516:Prothrombin / Q000502:physiology; D013915:Thrombasthenia / Q000201:enzymology; D013917:Thrombin / Q000502:physiology; D013925:Thromboplastin / Q000097:blood
D008563:Membrane Lipids; D010743:Phospholipids; D005165:Factor V; D011516:Prothrombin; D005170:Factor X; D013925:Thromboplastin; D010741:Phospholipases A; D013917:Thrombin