Alpha granule proteins in type I von Willebrand's disease.
Platelet von Willebrand factor (vWf) is located in the alpha granules. Individuals with type I von Willebrand's disease (vWd) with prolonged bleeding times are best discriminated from those who have normal bleeding times by the normal level of platelet vWf ristocetin cofactor activity (vWf activity) and, to a lesser extent, by their platelet vWf antigen content. We have studied the content of adhesive proteins and platelet factor-4 (PF-4), and beta-thromboglobulin (beta TG) in the platelet alpha granules of types I and III vWd patients to determine if other alterations in alpha granule contents of proteins occur in vWd. We found that type I vWd patients with prolonged or normal bleeding times could not be differentiated on the basis of their platelet levels of beta TG, PF-4, fibronectin, or fibrinogen. The levels of the alpha granule constituents in the type I vWd patient were similar to normal except for the platelet fibrinogen concentration. Patients with type I vWd, regardless of the level of platelet vWf activity of antigen, had increased levels of platelet fibrinogen. The patients with type III vWd who had undetectable levels of platelet and plasma vWf also had increased levels of platelet fibrinogen. In our study we could not attribute the variation in the platelet vWf activity and antigen in type I vWd to the size of the alpha granule pool as determined by the measurement of other alpha granule proteins. The mechanism(s) of increased platelet fibrinogen in these vWd patients is at present unknown.
McKeown
L P
LP
Hematology Service Clinical Center, NIH, Bethesda, MD 20892.
Williams
S B
SB
Shafer
B
B
Murray
N
N
Gralnick
H R
HR
D000941:Antigens / Q000032:analysis; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005340:Fibrinogen / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D010978:Platelet Factor 4 / Q000378:metabolism; D012016:Reference Values; D001620:beta-Thromboglobulin / Q000378:metabolism; D014842:von Willebrand Diseases / Q000097:blood*; D014841:von Willebrand Factor / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D001798:Blood Proteins; D005353:Fibronectins; C029417:Von Willebrand antigen; D001620:beta-Thromboglobulin; D014841:von Willebrand Factor; D010978:Platelet Factor 4; D005340:Fibrinogen