Determinants of bleeding phenotype in adult patients with moderate or severe von Willebrand disease

Thromb Haemost. 2012 Oct;108(4):683-92. doi: 10.1160/TH12-04-0244. Epub 2012 Aug 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Blood Group Antigens
  • Cohort Studies
  • Cross-Sectional Studies
  • Factor VIII / metabolism
  • Female
  • Hemorrhage / blood
  • Hemorrhage / etiology*
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Phenotype
  • Risk Factors
  • Sex Characteristics
  • Young Adult
  • von Willebrand Disease, Type 1 / blood
  • von Willebrand Disease, Type 1 / complications
  • von Willebrand Disease, Type 2 / blood
  • von Willebrand Disease, Type 2 / complications
  • von Willebrand Disease, Type 3 / blood
  • von Willebrand Disease, Type 3 / complications
  • von Willebrand Diseases / blood
  • von Willebrand Diseases / classification
  • von Willebrand Diseases / complications*
  • von Willebrand Factor / metabolism

Substances

  • Blood Group Antigens
  • von Willebrand Factor
  • Factor VIII