Factor V Quebec revisited.
Factor V Quebec has been described as a bleeding disorder that exhibits an autosomal dominant inheritance pattern and presents severe bleeding after trauma. Two members of a fourth-generation (IV.13 and IV.15) Canadian family have been studied in detail and are the subject of this report. Their clinical presentations and histories have been described previously (Tracy et al: J Clin Invest 74:1221, 1984). Persistent abnormalities include mild thrombocytopenia and defective platelet factor V. Plasma factor V is present at near normal concentration and is fully functional. Thus, the bleeding diathesis appears to reflect the absence of platelet factor V activity. The recent report (Hayward et al: Blood 84:110a, 1994 [suppl, abstr]) of multimerin deficiency in these individuals led us to reevaluate these patients. Western blot analyses of platelet lysates developed with a variety of monoclonal antibodies show that the alpha-granule proteins, fibrinogen, von Willebrand factor, factor V and osteonectin are decreased in concentration and significantly degraded in the platelets of these patients. Thrombospondin, while not degraded, is substantially decreased. In contrast, platelet factor 4 and beta-thromboglobulin do not appear to be affected. These observations suggest that the alpha-granules are correctly assembled but the contents are subsequently subjected to proteolytic degradation. The results indicate that factor V Quebec disorder is probably associated with a generalized defect that leads to degradation of most proteins of the alpha-granules.
Janeway
C M
CM
Department of Biochemistry, University of Vermont, College of Medicine, Burlington 05404-0068, USA.
Rivard
G E
GE
Tracy
P B
PB
Mann
K G
KG
D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics; D002170:Canada; D004797:Enzyme-Linked Immunosorbent Assay; D005165:Factor V / Q000032:analysis* / Q000235:genetics; D005166:Factor V Deficiency / Q000097:blood* / Q000235:genetics; D006801:Humans; D015151:Immunoblotting
D001798:Blood Proteins; D005165:Factor V