In:
Pathophysiology of Haemostasis and Thrombosis, S. Karger AG, Vol. 28, No. 6 ( 1998), p. 289-300
Kurzfassung:
In a final stage of activation, platelets become procoagulant because of the appearance of phosphatidylserine (PS) at the membrane outer surface. This PS exposure requires a rise in cytosolic [Ca 〈 sup 〉 2+ 〈 /sup 〉 ] 〈 sub 〉 i 〈 /sub 〉 , is accompanied by formation of membrane blebs, and stimulates the formation of thrombin from its precursor prothrombin. Here, we investigated whether thrombin, as a potent platelet agonist, can induce this procoagulant response in plasma-free platelets interacting with fibrin or fibrinogen through their integrin α 〈 sub 〉 IIb 〈 /sub 〉 β 〈 sub 〉 3 〈 /sub 〉 receptors. First, in platelets that were stimulated to spread over fibrin or fibrinogen surfaces with adrenaline, addition of thrombin and CaCl 〈 sub 〉 2 〈 /sub 〉 caused a potent Ca 〈 sup 〉 2+ 〈 /sup 〉 signal that in about 30% of the cells was accompanied by exposure of PS. At low doses, integrin α 〈 sub 〉 IIb 〈 /sub 〉 β 〈 sub 〉 3 〈 /sub 〉 receptor antagonist (RGD peptide) inhibited platelet spreading as well as thrombin-evoked PS exposure. Second, in platelet-fibrinogen microaggregates that were preformed in the presence of adrenaline, thrombin/CaCl 〈 sub 〉 2 〈 /sub 〉 induced PS exposure and bleb formation of about 35% of the cells. Third, a potent, thrombin-dependent stimulation of prothrombinase activity was measured in platelet suspensions that were incubated with a fibrin clot. These results indicate that, in the absence of coagulating plasma, thrombin is a moderate inducer of the procoagulant response of platelets, once integrin α 〈 sub 〉 IIb 〈 /sub 〉 β 〈 sub 〉 3 〈 /sub 〉 -mediated interactions are stimulated (by adrenaline) and CaCl 〈 sub 〉 2 〈 /sub 〉 is present.
Materialart:
Online-Ressource
ISSN:
1424-8832
,
1424-8840
Sprache:
Englisch
Verlag:
S. Karger AG
Publikationsdatum:
1998
ZDB Id:
2081182-2
