Common Risk Factors Add to Inherited Thrombophilia to Predict Venous Thromboembolism Risk in Families

Area of Science:

• Cardiovascular Medicine
• Genetics
• Epidemiology

Background:

• Venous thromboembolism (VTE) exhibits significant heterogeneity in affected families, despite shared thrombophilia defects.
• Accurate VTE risk assessment tools are crucial for managing families with inherited thrombophilia.

Purpose of the Study:

• To investigate the contribution of common environmental and genetic factors to VTE risk heterogeneity in families with inherited thrombophilia.
• To develop and validate a risk score integrating thrombophilia status with common risk factors.

Main Methods:

• Recruitment of 2,214 relatives from 651 families with known inherited thrombophilia.
• Systematic thrombophilia screening, genotyping for common genetic factors (ABO, F11, FGG polymorphisms), and collection of environmental data (BMI, smoking).
• Development of a multi-item risk score and evaluation of its discriminative ability for VTE.

Main Results:

• VTE incidence increased with thrombophilia severity (1.74 to 6.40 per 1,000 person-years).
• Obesity, smoking, ABO blood group, F11_rs2036914, and FGG_rs2066865 polymorphisms were associated with VTE.
• A risk score effectively stratified VTE risk in mild thrombophilia patients and showed good discrimination (AUC=0.702) when combined with thrombophilia status.

Conclusions:

• Integrating common environmental and genetic risk factors significantly improves VTE risk assessment in individuals with inherited thrombophilia.
• The developed risk score offers a valuable tool for personalized VTE risk management in at-risk families.