Relationship between plasma tissue Factor Pathway Inhibitor (TFPI) levels, thrombin generation and clinical risk of bleeding in patients with severe haemophilia A or B.

Autor: Tardy-Poncet B; Université Jean Monnet Saint-Étienne, CHUSaint-Étienne, Centre de traitement de l'hémophilie, Mines Saint-Etienne, INSERM, SAINBIOSE U1059, Saint-Etienne, France.; Inserm CIC 1408, CHU Saint-Étienne, Saint-Etienne, France., Montmartin A; Université Jean Monnet Saint-Étienne, Mines Saint-Etienne, INSERM, SAINBIOSE U1059, Saint-Etienne, France., Chambost H; Hôpital Timone, Centre de Traitement de l'Hémophilie, Assistance Publique-Hôpitaux de Marseille, Marseille, France., Lienhart A; Hôpital Cardiologique Louis Pradel, Centre de Référence de l'Hémophilie, Lyon, France., Frotscher B; Centre de Traitement de l'Hémophilie, CHU de Nancy, Nancy, France., Morange PE; INSERM, INRAE, C2VN, Laboratoire d'Hématologie, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France., Falaise C; Hôpital Timone, Centre de Traitement de l'Hémophilie, Assistance Publique-Hôpitaux de Marseille, Marseille, France., Collange F; Inserm CIC 1408, CHU Saint-Étienne, Saint-Etienne, France., Dargaud Y; Hôpital Cardiologique Louis Pradel, Centre de Référence de l'Hémophilie, Lyon, France.; UR 4609 Hémostase & Thrombose, Université Claude Bernard Lyon 1, Lyon, France., Toussaint-Hacquard M; Laboratoire d'Hématologie Biologique, CHU Nancy-Brabois, Vandoeuvre-Les-Nancy, France., Ardillon L; Centre de Traitement de l'Hémophilie, CHU de Tours, Tours, France., Wibaut B; Centre de Ressources et de Compétences des Maladies Hémorragiques Constitutionnelles Rares, Centre de Référence Maladie de Willebrand, CHU Lille, Lille, France., Jeanpierre E; Laboratoire d'Hémostase, Pôle de Biologie Pathologie Génétique Médicale, CHU Lille, Lille, France., Nguyen P; Laboratoire d'Hématologie, CHU Reims, Reims, France., Volot F; Centre de Traitement de l'Hémophilie, CHU Dijon, Dijon, France., Tardy B; Inserm CIC 1408, CHU Saint-Étienne, Saint-Etienne, France.; Université Jean Monnet Saint-Étienne, Mines Saint-Etienne, INSERM, SAINBIOSE U1059, Saint-Etienne, France.
Jazyk: angličtina
Zdroj: Haemophilia : the official journal of the World Federation of Hemophilia [Haemophilia] 2024 May; Vol. 30 (3), pp. 693-701. Date of Electronic Publication: 2024 Apr 22.
DOI: 10.1111/hae.15020
Abstrakt: Introduction: Bleeding severity in severe haemophilic patients, with low thrombin generation (TG) capacity, can vary widely between patients, possibly reflecting differences in tissue factor pathway inhibitor (TFPI) level.
Aim: To compare free TFPI (fTFPI) levels in patients with severe haemophilia A (sHA) and severe haemophilia B (sHB) and to investigate in these patients as a whole the relationships between bleeding and TG potential, between TG potential and fTFPI level and between fTFPI level and bleeding tendency.
Methods: Data on bleeding episodes retrospectively recorded during follow-up visits over 5-10 years were collected and used to calculate the annualised joint bleeding rate (AJBR). fTFPI levels and basal TG parameters were determined in platelet-poor plasma (PPP) and platelet-rich plasma (PRP) using calibrated automated tomography (CAT).
Results: Mean fTFPI levels did not differ significantly between sHA (n = 34) and sHB (n = 19) patients. Mean values of endogenous thrombin potential (ETP) and thrombin peak (peak) in PPP and PRP were two-fold higher when fTFPI levels < 9.4 versus > 14.3 ng/mL. In patients treated on demand, ETP and peak in PRP were doubled when AJBR was ≤ 4.9 $ \le 4.9$ , AJBR being halved in patients with a low fTFPI level (9.4 ng/mL). In patients on factor prophylaxis, no association was found between TG parameters and either fTFPI level or AJBR.
Conclusion: In patients treated on demand, bleeding tendency was influenced by fTFPI levels, which in turn affected basal TG potential. In patients on prophylaxis, bleeding tendency is probably determined primarily by the intensity of this treatment.
(© 2024 The Authors. Haemophilia published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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