Characterization of calcium-dependent binding of endogenous factor VIII/von Willebrand factor to surface activated platelets.
Activation of washed platelets in the presence of EDTA with either 1 U/ml of alpha-thrombin or 2 microM calcium ionophore (A23187) caused the release of one-third to one-half of the platelet factor VIII/von Willebrand factor (FVIII/vWF) into the supernatant. When calcium was present in excess, only 10% of the platelet FVIII/vWF was detected free in the supernatant, regardless of whether calcium was present before stimulation or added to the platelets after thrombin activation. Release of [14C]serotonin and beta-thromboglobulin were not affected by divalent cations indicating that reduced supernatant levels of FVIII/vWF in the presence of calcium were not due to differential release, but were probably due to a calcium-dependent association of released FVIII/vWF with the platelet surface. The presence or absence of intact glycoprotein Ib on the platelet surface made no significant difference to the observed FVIII/vWF partition. Platelets from a patient with Glanzmann's thrombasthenia, however, failed to show a calcium effect with respect to released FVIII/vWF. The combined results suggest that as well as the ristocetin-dependent, divalent cation-independent binding of FVIII/vWF to glycoprotein Ib, there is a divalent cation-dependent binding of FVIII/vWF to the activated platelet surface which is mediated via the glycoprotein IIb/IIIa complex.
D001779:Blood Coagulation Factors / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D013917:Thrombin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism*
D001779:Blood Coagulation Factors; D006023:Glycoproteins; D014841:von Willebrand Factor; D000001:Calcimycin; D005169:Factor VIII; D013917:Thrombin; D002118:Calcium