Absence of the largest platelet-von Willebrand multimers in a patient with lactoferrin deficiency and a bleeding tendency.
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.
Parker
R I
RI
Clinical Pathology Department, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
McKeown
L P
LP
Gallin
J I
JI
Gralnick
H R
HR
D001704:Biopolymers; D001792:Blood Platelets / Q000378:metabolism*; D002648:Child; D004198:Disease Susceptibility; D006470:Hemorrhage / Q000097:blood*; D006801:Humans; D007781:Lactoferrin / Q000172:deficiency*; D008297:Male; D010979:Platelet Function Tests; D014841:von Willebrand Factor / Q000378:metabolism*
D001704:Biopolymers; D014841:von Willebrand Factor; D007781:Lactoferrin