Summary
We have studied a young male with lactoferrin deficiency and a bleeding tendency responsive
to cryoprecipitate. This child has had increased bleeding following surgical procedures
and a variably prolonged template bleeding time. The patient has a normal platelet
count, normal in vitro platelet ATP secretion and aggregation in response to a variety
of agonists, and normal concentration of plasma-von Willebrand factor ristocetin cofactor
activity and antigen. Analysis of plasma-vWf multimers by agarose gel electrophoresis
consistently demonstrated a subtle decrease in the largest vWf multimers. In contrast,
analysis of the patient’s platelet-vWf revealed normal vWf:Ag, decreased vWf ristocetin
cofactor activity, and a striking absence of the high and intermediate size molecular
weight vWf multimers. Analysis of surface bound platelet-vWf demonstrated normal amounts
on the surface of unstimulated platelets, but after thrombin stimulation the platelet-vWf
surface expression did not increase. This lack of increased platelet-vWf surface expression
resulted from decreased binding of secreted platelet-vWf to be surface of stimulated
platelets. These data suggest that the patient’s bleeding tendency may be related
to a defect in his platelet-vWf structure and/or mobilization. This case represents
a unique demonstration of an abnormality of platelet-vWf in the presence of normal
plasma-vWf, and supports the data indicating an important role for platelet-vWf in
primary hemostasis.
