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. 2025 Mar 11;9(5):1181-1184.
doi: 10.1182/bloodadvances.2024014785.

Platelet potential to switch to procoagulant phenotype compensates bleeding tendency in patients with hemophilia A

Karina Althaus  1   2   3 , Sophie Kieninger  1 , Anna Bäuerle  1 , Stefanie Hammer  1   2   3 , Nina Wolska  1   2 , Günalp Uzun  1   2 , Karoline Weich  1   2 , Lorenzo Alberio  4 , Alessandro Aliotta  4 , Christoph Faul  3   5 , Margarete Moyses  3   5 , Ursula Holzer  3   6 , Vanya Icheva  3   7 , David Gorodezki  3   6 , Sebastian Hörber  3   8 , Susan Halimeh  9 , Jan Zlamal  1   2 , Tamam Bakchoul  1   2   3
Affiliations

Platelet potential to switch to procoagulant phenotype compensates bleeding tendency in patients with hemophilia A

Karina Althaus et al. Blood Adv. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: K.A. received honoraria that were paid to the Medical University Hospital of Tuebingen for lectures from CSL Behring, Sobi, Meet The Experts, Expanda, and Werfen; and research grants that were paid to the Medical University Hospital of Tuebingen from Octapharma, Bayer, and Takeda. T.B. has received research funding from CoaChrom Diagnostica GmbH, Deutsche Forschungsgemeinschaft, Robert Bosch GmbH, Stiftung Transfusionsmedizin und Immunhämatologie e.V., Ergomed, DRK Blutspendedienst, Deutsche Herzstiftung, Ministerium fuer Wissenschaft, and Forschung und Kunst Baden-Wuerttemberg; has received lecture honoraria from Aspen Germany GmbH, Bayer Vital GmbH, Bristol Myers Squibb GmbH & Co. KG, Doctrina Med AG, Meet The Experts Academy UG, Schoechl Medical Education GmbH, Stago GmbH, Mitsubishi Tanabe Pharma GmbH, Novo Nordisk Pharma GmbH, Leo Pharma GmbH, and Swedish Orphan Biovitrum GmbH; and has provided consulting services to Terumo, and expert witness testimony related to heparin-induced thrombocytopenia (HIT) and non-HIT thrombocytopenic and coagulopathic disorders. All of these disclosures are outside the current work (ie, not related to the current work). The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
PLT activation and procoagulant potential in PwHAs and carriers in comparison with HCs. (A) PLT aggregation after adenosine 5′-diphosphate (ADP) (2 μM) stimulation is significantly reduced in PwHAs when compared with HCs. (B) No significant correlation between ADP (2 μM) response and ISTH-BAT bleeding scores. (C) No significant correlation between ADP (2 μM) response and ABR. (D) PCPs after thrombin (10 U/mL)/convulxin (CVX) (0.5 μg/mL) stimulation are significantly increased in PwHAs and carriers when compared with HCs. (E) Higher PCP percentages correlate negatively with ISTH-BAT bleeding score, indicating that increased PCP levels are associated with lower bleeding severity. (F) Higher PCP percentages correlate negatively with the ABR, suggesting that elevated PCP levels are linked to a reduced bleeding frequency. Each dot represents an individual patient categorized by hemophilia severity, categorized as severe (red), moderate (yellow), mild (green), carrier (white), and HC (blue).
Figure 2.
Figure 2.
Calcium influx and thrombin generation in PLTs from PwHAs and HCs. (A -B) Calcium influx after thrombin stimulation is significantly elevated in PwHAs when compared with HCs. (C) Thrombin generation is higher in PwHAs with increased procoagulant activity upon TRAP-6/CVX stimulation. (D) Enhanced thrombin generation (endogenous thrombin potential [ETP]) is observed in both HC and PwHA upon  thrombin receptor activating peptide-6 (TRAP-6)/CVX stimulation when compared with buffer stimulation. (E) PCP levels (CD62p+/PS+ %) positively correlate with ETP in PwHAs and HCs. (F) PCP level is significantly correlated with reduced thrombin generation lag time. Each dot represents an individual patient categorized by hemophilia severity, categorized as severe (red), moderate (yellow), mild (green), carrier (white), and HC (blue).
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