• Normally, activated protein C (APC) inactivates factor V in the clotting cascade → decreases the activation of thrombin.
• A DNA point mutation substitutes guanine for adenine → corresponding mRNA codon forms glutamine in place of arginine on position 506 (Arg506Gln mutation) near the polypeptide cleavage site of factor V
• In such patients, Gln506-Va is resistant to cleavage by APC → factor V remains active → activates prothrombin → increases thrombotic events (e.g., peripheral and cerebral vein thrombosis, recurrent pregnancy loss)
• Risk of thromboembolism is several times higher in patients with homozygous mutations than in those with heterozygous mutations.