Effect of calcium ion concentration on the ability of fibrinogen and von
Willebrand factor to support the ADP-induced aggregation of human platelets
EJ Harfenist, MA Packham, RL Kinlough-Rathbone, M Cattaneo and JF Mustard
To investigate the suggestion that von Willebrand factor (vWf) can
substitute for fibrinogen in supporting ADP-induced aggregation of human
platelets, we studied platelet reactions in two media: (1) a high calcium
medium, Tyrode-albumin solution containing calcium ions in the
physiological range of 2 mmol/L, and (2) a low calcium medium, modified
Tyrode-albumin solution from which calcium salt was omitted (calcium ion
concentration approximately 20 mumol/L). In the high calcium medium vWf
even at concentrations up to six times as high as physiological, showed
little or no potentiation of ADP-induced platelet aggregation, whereas
fibrinogen strongly potentiated reversible aggregation without thromboxane
formation or release of granule contents. In the low calcium medium, either
vWf or fibrinogen supported biphasic aggregation in response to ADP, with
thromboxane formation and release of granule contents. Aspirin and the
thromboxane receptor blocker BM 13.177 inhibited these secondary responses
to von Willebrand factor, indicating that they require thromboxane A2
formation and feedback amplification by thromboxane A2. A monoclonal
antibody, 10E5, to the platelet glycoprotein IIb/IIIa complex inhibited
both primary and secondary aggregation. Although vWf supports ADP-induced
aggregation when the concentration of ionized calcium is in the micromolar
range, it does not support ADP-induced aggregation in the presence of a
concentration of ionized calcium in the physiological range, indicating
that vWf probably cannot substitute for fibrinogen in supporting ADP-
induced aggregation in vivo.
Volume 70,
Issue 3,
pp. 827-831,
09/01/1987
Copyright © 1987 by The American Society of Hematology
