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    Poster Networking

    Hemophilia and Rare Bleeding Disorders

    Poster Networking Session

    PB0659 - Patients with hemophilia A have increased levels of circulating activated protein C: potential contribution to their hemostatic status

    Monday, June 26, 2023
    18:30 – 19:30 ET
    Room: Exhibition

      Co-Author(s)

    • Julia Oto

      Postdoctoral Researcher
      Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

      • Presenting Author(s)

    • Raquel Herranz, MSc (she/her/hers)

      PhD Candidate
      Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

      • Co-Author(s)

    • FC

      Fernando Cana

      Laboratory Technician
      Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

    • AM

      Antonio Moscardo

      Postdoctoral Researcher
      Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Thrombosis and Haemostasis Unit, Haematology Service, La Fe University and Polytechnic Hospital, Valencia, Spain.
      Valencia, Comunidad Valenciana, Spain

    • MC

      Maria Castaño

      Researcher
      Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

    • IA

      Isabel Aleman-Cabrera

      PhD Student
      Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

    • EP

      Emma Plana

      Postdoctoral Researcher
      Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Angiology and Vascular Surgery Service, La Fe University and Polytechnic Hospital, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

    • LG

      Luis Gomez-Cambronero

      Medical doctor
      Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Thrombosis and Haemostasis Unit, Haematology Service, La Fe University and Polytechnic Hospital, Valencia, Spain.
      Valencia, Comunidad Valenciana, Spain

    • AC

      Ana Cid

      Medical doctor
      Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Thrombosis and Haemostasis Unit, Haematology Service, La Fe University and Polytechnic Hospital, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

    • SH

      Saturnino Haya

      Medical doctor
      Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Thrombosis and Haemostasis Unit, Haematology Service, La Fe University and Polytechnic Hospital, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

    • SB

      Santiago Bonanad

      Head of Thrombosis and Hemostasis Unit
      Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain; Thrombosis and Haemostasis Unit, Haematology Service, La Fe University and Polytechnic Hospital, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

    • PM

      Pilar Medina

      PI
      Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

    Background: The hemorrhagic phenotype of hemophilia A (HA) differs among patients, even with apparently identical clinical forms. One hypothesis is an imbalance in the natural anticoagulants.

    Aims: To analyze the levels of activated protein C (APC) in plasma of HA patients and carriers and to correlate their levels with the hemostatic status, hitherto unknown.

    Methods: We recruited 100 HA patients (59 severe, 11 moderate, 30 mild) in a stable clinical situation and 48–72 h after factor administration and 21 HA carriers. We quantified the levels of circulating APC, coagulation factors (FVIII, FV, fibrinogen, FIX, FXI, FXII, FX, FII, FVII, FVW), PC, protein S (PS), antithrombin (AT) and the thrombin generation test (TGT) with the BleedScreen ST Genesia (Stago).

    Results: All HA patients had higher circulating APC levels than carriers (7.5 vs. 5.1 ng/mL, P=0.012) and its cofactor PS (115.6 vs. 94.3%, P< 0.001), while they had similar PC levels. AT levels were similar in both groups. They had lower levels of FVIII, FXII, and of the TGT peak, time to peak, ETP, velindex and start tail (P < 0.001). When patients were analyzed by severity (severe, moderate, and mild), APC levels increased with HA severity, and TGT slightly decreased. Finally, HA severity correlated with APC (0.196, P=0.037), peak (-0.595), ETP (-0.460), velindex (-0.604) and start tail (0.672) (P < 0.0001 in all cases), as well APC levels and peak (-0.242, P=0.016) and ETP (-0.272, P=0.006).

    Conclusion(s): HA patients have higher circulating APC levels than carriers, which increases with severity despite having similar levels of PC. Other anticoagulants like AT are unaltered and HA patients have a lower capacity to generate thrombin. Furthermore, APC levels correlate with HA severity and TGT. Thus, APC seems to modulate the hemostatic status of HA patients and could perhaps modulate their bleeding phenotype. SOBI, ISCIII-FEDER (PI20/00075, FI21/00171), GVA-CIACIF/2021/192 and SETH.