PO019 | LONGITUDINAL COAGULATION PROFILING BY THROMBIN GENERATION AND CIRCULATING MICROVESISCLES OF INDIVIDUALS UNDERGOING GENDER-AFFIRMING HORMONE THERAPY

@article{campello2026po019,
  title = {{PO019 | LONGITUDINAL COAGULATION PROFILING BY THROMBIN GENERATION AND CIRCULATING MICROVESISCLES OF INDIVIDUALS UNDERGOING GENDER-AFFIRMING HORMONE THERAPY}},
  author = {Elena Campello},
  journal = {Bleeding, Thrombosis and Vascular Biology},
  year = {2026},
  month = oct,
  url = {https://www.btvb.org/btvb/article/view/835},
  note = {CC BY-NC},
}

TY  - JOUR
TI  - PO019 | LONGITUDINAL COAGULATION PROFILING BY THROMBIN GENERATION AND CIRCULATING MICROVESISCLES OF INDIVIDUALS UNDERGOING GENDER-AFFIRMING HORMONE THERAPY
AU  - Elena Campello
PY  - 2026
DA  - 2026/10/26
JO  - Bleeding, Thrombosis and Vascular Biology
UR  - https://www.btvb.org/btvb/article/view/835
AB  - Background and aims. Transgender individuals may have an increased thrombotic risk related to gender-affirming hormone therapy (GAHT). We aimed to investigate longitudinal GAHT-related changes in coagulation and explore mechanisms underlying hypercoagulability. Methods. Prospective longitudinal study enrolling adult transgender individuals initiating GAHT. Blood samples were collected at baseline and follow-up up to 24 months. Hemostatic profiling included procoagulant factors, natural anticoagulants, global assays, thrombin generation (PPP, calibrated automated thrombogram), and large extracellular vesicles (MVs) by flow cytometry. Clinical events were recorded. Results. The cohort included 44 Assigned Male at Birth (AMAB) and 52 Assigned Female at Birth (AFAB) participants. Over follow-up, AMAB individuals showed a progressive procoagulant shift. Factor VIII increased significantly over time; p for trend=0.04). Natural anticoagulant pathways significantly changed, with longitudinal variations in free protein S antigen (p=0.03), protein S activity (p=0.02), and antithrombin (p=0.009). Thrombin generation increased, with shortening of lag time (p=0.005) and marked increases in peak thrombin (p<0.001), ETP (p=0.04), and ETP ratio (p=0.005). Consistently, ROTEM showed faster clot initiation with shortening of EXTEM-CT (p<0.001) (Table 1). In AFAB individuals, factor VIII and fibrinogen did not significantly change. Protein C activity decreased over time (p=0.01), while free protein S antigen (p=0.05), protein S activity (p=0.03), and antithrombin (p=0.02) showed longitudinal variations. TG lag time decreased (p=0.005) and peak thrombin increased (p<0.001), whereas ETP and ETP ratio remained unchanged. On ROTEM, clot propagation was impaired, as indicated by increased INTEM-CFT (p<0.001) and EXTEM-CFT (p=0.002), along with reduced INTEM-MCF (p=0.04) (Table 1). In AMAB participants, total circulating Annexin V+ MVs significantly increased over follow-up (p for trend=0.0009), while erythrocyte-derived MVs (Annexin V+ CD235a+) decreased over follow-up (p=0.0156), with lower levels already evident at 3 months and persisting up to 24 months. In AFAB, platelet-derived MVs (Annexin V+ CD41+CD62P+) varied over follow-up (p=0.0146), suggesting time-dependent modulation after testosterone initiation, with early changes at 3 months (Table1). Conclusions. GAHT induces sex-specific coagulation changes. AMAB develop a progressive procoagulant phenotype with increased thrombin generation and faster clot initiation, while AFAB show a distinct profile involving thrombin peak and clot propagation, accompanied by MV modulation. These findings support different mechanisms of GAHT-related hypercoagulability.
SN  - 2785-5309
ER  -