Factor V Quebec Revisited

• Published in: Blood 1996-05, Vol.87 (9), p.3571-3578
• Main Authors: Janeway, Claude M., Rivard, Georges E., Tracy, Paula B., Mann, Kenneth G.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood Proteins - analysis; Blood Proteins - genetics; Canada; Enzyme-Linked Immunosorbent Assay; Factor V - analysis; Factor V - genetics; Factor V Deficiency - blood; Factor V Deficiency - genetics; Hematologic and hematopoietic diseases; Humans; Immunoblotting; Medical sciences; Platelet diseases and coagulopathies
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V87.9.3571.bloodjournal8793571

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 α-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 β-thromboglobulin do not appear to be affected. These observations suggest that the α-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 α-granules.