Unfavorably altered plasma clot properties in women with a HERDOO2 score equal to or greater than 2 and prediction of recurrent venous thromboembolism

The HERDOO2 rule can help identify patients in whom anticoagulation can be safely discontinued. Unfavorably altered fibrin clot properties predict recurrent venous thromboembolism (VTE). We aimed to assess a possible association between fibrin clot properties and the HERDOO2 score in women after unprovoked VTE. Eighty women younger than 70 years after a first unprovoked VTE separately and combined with 32 women after hormone‑related VTE were followed for a median of 48.5 months (interquartile range, 37.5-67 years). Plasma fibrin clot permeability $K_{s}$, lysability, turbidity measurements, and thrombin generation were assessed 3 months after the index event in relation to the HERDOO2 score. Nineteen women (23.8%) with a HERDOO2 score equal to or higher than 2 were characterized by lower $K_{s}$ (-6.8%), indicating formation of more compact clots, impaired fibrinolysis as evidenced by a reduced maximum rate of D‑dimer release from clots $D‑D_{rate}$, by 6.8%), and prolonged clot lysis time (CLT, by 23.8%). No increased thrombin generation or differences in the remaining fibrin clot properties were observed. When combined with estrogen‑related VTE, the same trends were observed. $D-D_{rate}$ and CLT correlated with the HERDOO2 score (r = -0.28, P = 0.01 and r = 0.35, P = 0.002, respectively) in 80 women with unprovoked VTE. Unfavorable clot phenotype, defined as $K_{s}$ ≤6.55×10-9 cm2 and CLT >99.5 minutes, was associated with high risk of recurrence in the HERDOO2 rule (P = 0.02). We showed that middle‑aged women after unprovoked VTE with high risk of recurrence based on the HERDOO2 rule are characterized by formation of denser fibrin clots and impaired fibrinolysis.