What are the normal levels of von Willebrand factor (VWF) antigen and activity in the first trimester?

Normal Levels of von Willebrand Factor (VWF) Antigen and Activity in First Trimester

Normal von Willebrand factor (VWF) levels increase significantly during pregnancy, with VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo) typically rising above the non-pregnant reference range of 50-200 IU/dL during the first trimester.

Normal VWF Reference Values

• Non-pregnant reference range:

  • VWF:Ag: 50-200 IU/dL
  • VWF:RCo: 50-200 IU/dL
  • VWF:RCo/VWF:Ag ratio: >0.5-0.7 1

• First trimester changes:

  • VWF levels begin increasing early in pregnancy
  • Progressive increase occurs throughout gestation 2
  • Factor VIII shows a less dramatic increase than VWF 3

Factors Affecting VWF Levels in Pregnancy

• Blood group influence:

  • Individuals with blood group O have VWF levels approximately 25% lower than other ABO blood groups 1
  • Factor VIII is significantly lower in blood group O (p=0.035) 3

• Ethnicity considerations:

  • African-Americans have higher baseline VWF levels than Caucasians 1

• Other influencing factors:

  • Stress, anxiety, and recent exercise can falsely elevate VWF levels 1
  • Inflammatory conditions may increase VWF levels 1
  • No significant differences in VWF levels between primigravidae and multigravidae 3

Clinical Implications

• Bleeding risk assessment:

  • Bleeding complications during pregnancy are more frequent when VWF:RCo and Factor VIII levels are <50 IU/dL 4
  • Women with von Willebrand disease often experience improvement in their condition during pregnancy due to increasing VWF levels 5

• Laboratory considerations:

  • VWF propeptide (VWFpp) increases later in pregnancy than VWF:Ag 2
  • VWFpp:VWF:Ag ratios progressively decrease during pregnancy 2
  • ADAMTS13 activity remains unchanged during pregnancy 2

Important Testing Considerations

• Sample handling:

  • Blood samples for VWF assays should be transported at room temperature
  • Plasma should be separated promptly at room temperature
  • If testing within 2 hours, keep samples at room temperature
  • For storage/transport, freeze promptly at or below -40°C 1

• Test interpretation:

  • VWF assays have relatively high coefficients of variation (10-30%)
  • VWF:RCo assay has particularly high variability
  • Consider using WHO-linked calibrators for standardized reporting 1

When evaluating VWF levels in first trimester pregnancy, it's essential to consider the physiologic increase that occurs and interpret results in the context of the patient's baseline levels, blood type, and clinical presentation.