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Peer-reviewedCC BY-NCEJHaem

An In Vitro Study Simulating Prophylactic Anticoagulation in Haemophilia A and B

  • Nicoletta Riva1
  • Kevin Vella2
  • Kieron Hickey3
  • Nigel Debattista4
  • Carmel Grima2
  • Denise Borg‐Aquilina5
  • Liberato Camilleri6
  • Jiong Jiong Guo7
  • Alexander Gatt1,2
7 affiliations
  1. 1Department of Pathology Faculty of Medicine and Surgery University of Malta Msida Malta
  2. 2Coagulation Laboratory Department of Pathology Mater Dei Hospital Msida Malta
  3. 3Sheffield Haemophilia and Thrombosis Centre University of Sheffield Sheffield UK
  4. 4Department of Applied Biomedical Science Faculty of Health Sciences University of Malta Msida Malta
  5. 5National Blood Transfusion Service Pietà Malta
  6. 6Department of Statistics & Operations Research Faculty of Science University of Malta Msida Malta
  7. 7Department of Orthopedics and Sports Medicine The First Affiliated Hospital of Soochow University Suzhou Jiangsu People's Republic of China
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Abstract

Introduction: Patients with haemophilia A (HA) and haemophilia B (HB) are at increased bleeding risk. A recent guidance document suggests considering pharmacological thromboprophylaxis on a case‐by‐case basis in these patients undergoing surgery at high‐risk of venous thromboembolism. This study aimed to assess the effect of prophylactic doses of three anticoagulants (enoxaparin, rivaroxaban and unfractionated heparin [UFH]) on in vitro models of HA and HB.

Methods: FVIII‐ and FIX‐deficient plasma were spiked with FVIII and FIX concentrates to mimic severe, moderate and mild HA (FVIII concentrations < 1%, 1.2% and 17.0%, respectively) and HB (FIX concentrations < 1%, 3.9% and 22.9%, respectively). Each pool was spiked with enoxaparin (concentration range 0.3–0.4 IU/mL), rivaroxaban (50–100 ng/mL) and UFH (0.2–0.3 IU/mL). The following assays were performed: prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin generation (using the semi‐automated fluorogenic calibrated automated thrombin generation assay [CAT]).

Results: The PT was not significantly affected by the anticoagulants. A significant prolongation of the APTT was observed; UFH showed the greatest increase, followed by rivaroxaban and enoxaparin. All anticoagulants impacted on the CAT curves. UFH showed the greatest reduction of the endogenous thrombin potential; rivaroxaban showed the greatest increase of lag time and time to peak. Peak thrombin and velocity index were similarly reduced by rivaroxaban and UFH, whereas enoxaparin was associated with smaller changes in all parameters.

Conclusion: A significant effect of three prophylactic anticoagulants was observed in factor‐deficient plasmas. This study provides further insight into this topic and supports the concept of an individualised approach to haemophilia patients.

Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission

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Cite

BibTeXRIS
BibTeX
@article{riva2026vitro,
  title = {{An In Vitro Study Simulating Prophylactic Anticoagulation in Haemophilia A and B}},
  author = {Nicoletta Riva and Kevin Vella and Kieron Hickey and Nigel Debattista and Carmel Grima and Denise Borg‐Aquilina and Liberato Camilleri and Jiong Jiong Guo and Alexander Gatt},
  journal = {EJHaem},
  year = {2026},
  month = oct,
  doi = {10.1002/jha2.70314},
  url = {https://europepmc.org/article/PMC/PMC13720666},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - An In Vitro Study Simulating Prophylactic Anticoagulation in Haemophilia A and B
AU  - Nicoletta Riva
AU  - Kevin Vella
AU  - Kieron Hickey
AU  - Nigel Debattista
AU  - Carmel Grima
AU  - Denise Borg‐Aquilina
AU  - Liberato Camilleri
AU  - Jiong Jiong Guo
AU  - Alexander Gatt
PY  - 2026
DA  - 2026/10/30
JO  - EJHaem
DO  - 10.1002/jha2.70314
UR  - https://europepmc.org/article/PMC/PMC13720666
AB  - Introduction: Patients with haemophilia A (HA) and haemophilia B (HB) are at increased bleeding risk. A recent guidance document suggests considering pharmacological thromboprophylaxis on a case‐by‐case basis in these patients undergoing surgery at high‐risk of venous thromboembolism. This study aimed to assess the effect of prophylactic doses of three anticoagulants (enoxaparin, rivaroxaban and unfractionated heparin [UFH]) on in vitro models of HA and HB.  Methods: FVIII‐ and FIX‐deficient plasma were spiked with FVIII and FIX concentrates to mimic severe, moderate and mild HA (FVIII concentrations < 1%, 1.2% and 17.0%, respectively) and HB (FIX concentrations < 1%, 3.9% and 22.9%, respectively). Each pool was spiked with enoxaparin (concentration range 0.3–0.4 IU/mL), rivaroxaban (50–100 ng/mL) and UFH (0.2–0.3 IU/mL). The following assays were performed: prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin generation (using the semi‐automated fluorogenic calibrated automated thrombin generation assay [CAT]).  Results: The PT was not significantly affected by the anticoagulants. A significant prolongation of the APTT was observed; UFH showed the greatest increase, followed by rivaroxaban and enoxaparin. All anticoagulants impacted on the CAT curves. UFH showed the greatest reduction of the endogenous thrombin potential; rivaroxaban showed the greatest increase of lag time and time to peak. Peak thrombin and velocity index were similarly reduced by rivaroxaban and UFH, whereas enoxaparin was associated with smaller changes in all parameters.  Conclusion: A significant effect of three prophylactic anticoagulants was observed in factor‐deficient plasmas. This study provides further insight into this topic and supports the concept of an individualised approach to haemophilia patients.  Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission
SN  - 2688-6146
ER  -