Clinical and prognostic implications of low or high level of von Willebrand factor in patients with Waldenstrom macroglobulinemia.
Acquired von Willebrand syndrome is described in patients with Waldenström macroglobulinemia (WM). Assessment of ristocetin cofactor activity (VWF:RCo) and von Willebrand factor (VWF) antigen (VWF:Ag) in 72 consecutive patients with WM showed a negative relation between VWF levels < 130 U/dL and both monoclonal immunoglobulin M concentration (mIgMC) and viscosity. Ten patients with VWF:RCo < 50 U/dL (< 40 for patients with blood group O) fulfilled the acquired von Willebrand syndrome criteria. They had higher mIgMC and viscosity. Reduction in mIgMC was associated with increase in VWF levels. The low VWF:RCo/VWF:Ag ratio suggested that high viscosity might be associated with increased shear force and cleavage of multimers. Surprisingly, 43 patients (59%) presented with high VWF:Ag (> 110 U/dL). They had higher bone marrow microvessel density and vascular endothelial growth factor expression on bone marrow mast cells. Five-year survival rates of patients with VWF:Ag < 110, between 110 and 250, and more than 250 U/dL were 96%, 71%, and 44%, respectively (P < .0001). High VWF:Ag was also a significant adverse prognostic factor for survival after first-line therapy (P < .0001), independently of the international scoring system. These results support systematic assessment of VWF in patients with WM. The adverse prognostic value of high VWF levels raises issues on interactions between lymphoplasmacytic cells, mast cells, and endothelial cells in WM.
Service d'Hématologie, Hôpital Schaffner, Lens, France.
Benedicte
B
Hivert
Claudine
C
Caron
Stephanie
S
Petit
Cecile
C
Charpy
Corinne
C
Fankam-Siaka
Stephanie
S
Lecocq
Christophe
C
Zawadzki
Sophie
S
Susen
Manuela
M
Rusu
Alain
A
Duhamel
Olivier
O
Tournilhac
Jenny
J
Goudemand
Pierre
P
Morel
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001809:Blood Viscosity; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis* / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism*
D014408:Biomarkers, Tumor; D007075:Immunoglobulin M; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor