Changes in von Willebrand factor and ADAMTS13 during IVF

Abstract

During IVF, circulating estradiol concentrations are strongly increased, and this may have direct effects on hemostasis. Elevated von Willebrand factor levels represent an important risk factor for arterial and venous thrombosis. ADAMTS13, also known as von Willebrand factor-cleaving protease, has an important regulatory function of von Willebrand factor but has not been studied during IVF. Blood was sampled from 31 women at maximal downregulation of estradiol synthesis using gonadotropin-releasing hormone analogues and during high-level stimulation of estradiol synthesis using follicle-stimulating hormone during the first phase of IVF. Von Willebrand factor antigen, von Willebrand factor ristocetin cofactor activity, factor VIII and ADAMTS13 antigen and activity levels in plasma were determined at the time of downregulation and at high-level stimulation. Estradiol increased from a mean of 154 pg/ml at downregulation to 5889 pg/ml at high-level stimulation (range 1620–19 500 pg/ml). Factor VIII increased from 0.96 ± 0.34 to 1.26 ± 0.41 kIU/l (P < 0.001). Von Willebrand factor antigen and activity increased from 0.75 ± 0.22 to 1.06 ± 0.40 kIU/l (P < 0.001) and from 0.83 ± 0.26 to 1.24 ± 0.48 kIU/l (P < 0.001), respectively. ADAMTS13 antigen decreased from 72.2 ± 13.5 to 67.9 ± 9.9% (P < 0.05, P = 0.01) and ADAMTS13 activity from 88.6 ± 18.3 to 80.8 ± 15.7% (P < 0.01). The increments in estradiol and factor VIII during IVF were paralleled by an increase in von Willebrand factor antigen and activity, and a decrease in circulating ADAMTS13 antigen and activity, respectively. This could in part explain why these patients have an increased risk of thrombotic events.