Determinants of bleeding phenotype in adult patients with moderate or severe von Willebrand disease.
We performed a nation-wide cross-sectional study to evaluate determinants of bleeding symptoms in a large unselected cohort of adults with von Willebrand disease (VWD). VWD patients were included (n=664), based on lowest historically measured VWF:Ag and VWF:Act levels ≤30 U/dl. Menorrhagia (85%), cutaneous bleeding (77%), bleeding from minor wounds (77%) and oral-cavity bleeding (62%) occurred most frequently. Higher age was associated with a higher bleeding score (BS), determined according to Tosetto, in females. A 10 year increase in age was associated with 0.8 point (95% confidence interval [CI] 0.4-1.1) higher BS. Females had higher BS than males (median 12 vs. 10, p=0.012). BS differed significantly between VWD type 1, 2 and 3: median 9 (-2-31), 13 (-1-33) and 19.5 (1-35), respectively (p<0.001). BS was strongly associated with VWF and FVIII levels: individuals with VWF:Ag levels ≤10 IU/dl, VWF:Act ≤10 IU/dl and FVIII:C ≤10 IU/dl had, respectively, 5.3 point (95%CI 3.2-7.3), 4.3 point (95%CI 2.9-5.8) and 9.6 point (95%CI 6.5-12.7) higher BS, than those with levels >30 IU/dl. In type 3 patients 1 IU/dl FVIII:C decrease was associated with 0.6 point (95% CI 0.1-1.1) BS increase (p=0.021). In conclusion, in VWD patients the bleeding phenotype is strongly associated with type of VWD and VWF and FVIII levels.
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Eva M
EM
de Wee
Yvonne V
YV
Sanders
Eveline P
EP
Mauser-Bunschoten
Johanna G
JG
van der Bom
Manon E L
ME
Degenaar-Dujardin
Jeroen
J
Eikenboom
Arja
A
de Goede-Bolder
Britta A P
BA
Laros-van Gorkom
Karina
K
Meijer
Karly
K
Hamulyák
Marten R
MR
Nijziel
Karin
K
Fijnvandraat
Frank W G
FW
Leebeek
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001789:Blood Group Antigens; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D012307:Risk Factors; D012727:Sex Characteristics; D055815:Young Adult; D056725:von Willebrand Disease, Type 1 / Q000097:blood / Q000150:complications; D056728:von Willebrand Disease, Type 2 / Q000097:blood / Q000150:complications; D056729:von Willebrand Disease, Type 3 / Q000097:blood / Q000150:complications; D014842:von Willebrand Diseases / Q000097:blood / Q000145:classification / Q000150:complications*; D014841:von Willebrand Factor / Q000378:metabolism
D001789:Blood Group Antigens; D014841:von Willebrand Factor; D005169:Factor VIII