In patients with hemophilia, a decreased thrombin generation profile is associated with a severe bleeding phenotype

Verhagen, Marieke J.A.; Bom, Johanna G. van der; Beckers, Erik A.M.; Blijlevens, Nicole M A; Coppens, Michiel; Gouw, Samantha C.; Jansen, Joop H.; Leebeek, Frank W.G.; Vulpen, Lize F D van; Meijer, Daniëlle; Schols, Saskia E. M.

doi:10.1016/j.rpth.2023.100062

Cited by 10 publications

(11 citation statements)

References 28 publications

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“…Some spontaneous bleeds may occur despite high trough levels, since a certain heterogeneity in clinical bleeding phenotype has been observed in hemophilia patients with similar FVIII or FIX activity levels. 31 Due to the observational nature, trough levels measurement was not compulsory. Therefore, it was not possible to temporally correlate FIX levels with break through bleeds/traumatic bleeds occurred during our study.…”

Section: Discussionmentioning

confidence: 99%

“…The goal of zero bleeding events is currently considered the target of prophylaxis, 1 to avoid/delay permanent joint damage, 2,27–30 indeed, the rate of subjects with zero bleedings with rIX‐FP at 2YFU was 84.6% ( N = 11), compared to 69.2% ( N = 9) of the previous treatment. Some spontaneous bleeds may occur despite high trough levels, since a certain heterogeneity in clinical bleeding phenotype has been observed in hemophilia patients with similar FVIII or FIX activity levels 31 . Due to the observational nature, trough levels measurement was not compulsory.…”

Section: Discussionmentioning

confidence: 99%

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Pattern of use and clinical outcomes with rIX‐FP in pediatric/adolescent patients with haemophilia B in Italy: Results from IDEAL real‐world study

Giordano,

Pollio,

Sottilotta

et al. 2024

European J of Haematology

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ObjectivesTo evaluate pattern of use and clinical outcomes in pediatric/adolescent patients enrolled in the IDEAL study.MethodsThis post‐hoc analysis of IDEAL retrospective‐prospective observational study focused on patients <18 years, 100% on prophylaxis during the entire observation period.ResultsThirteen subjects (median age 10.0 years; 61.5% ≤ 11 years) were analyzed. The infusion frequency changed from 2/week in 84.6% (N = 11) of patients with previous rFIX, to less than 1/weekly in 76.9% (N = 9) with rIX‐FP and the annualized number of infusions reduced of 57% (p = .002), from a mean ± SD of 95.1 ± 22.77 to 40.4 ± 6.79, respectively. Annualized mean consumption decreased of about 56% (p = .001), from 3748.4 ± 1155.40 IU/kg with previous rFIX, to 1656.8 ± 456.63 IU/kg of rIX‐FP. Mean FIX trough level changed from 3.0% ± 1.98% to 10.92% ± 3.6%. Low mean Annualized Bleeding Rate was maintained across all prophylaxis regimens (0.8 ± 1.69 vs. 0.3 ± 0.89) and zero bleeding patients moved from 69.2% (N = 9) with previous rFIX to 84.6% (N = 11) with rIX‐FP (p = .63). Two adverse events, none related to rIX‐FP, occurred in two patients. No inhibitors development was reported.ConclusionsThe results in this pediatric/adolescent subgroup support rIX‐FP prophylaxis may reduce infusion frequency, while providing high FIX trough levels, stable annualized bleeding rate and a good safety profile.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pattern of use and clinical outcomes with rIX‐FP in pediatric/adolescent patients with haemophilia B in Italy: Results from IDEAL real‐world study

Giordano,

Pollio,

Sottilotta

et al. 2024

European J of Haematology

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“…In the case of blood coagulation, an initial signal, i.e., endothelial damage, is exponentially amplified by the presence of zymogens or precursor proteins that are irreversibly activated by the action of proteases [ 69 , 70 ]. The participation of several zymogens, which are sequentially activated in one same pathway, such as the coagulation cascade, boosts the efficiency of signal amplification [ 71 ].…”

Section: Factor V a Procoagulant And Anticoagulant Proteinmentioning

confidence: 99%

The Magic of Proteases: From a Procoagulant and Anticoagulant Factor V to an Equitable Treatment of Its Inherited Deficiency

Pablo-Moreno

Miguel-Batuecas

Sancha

et al. 2023

IJMS

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Proteostasis, i.e., the homeostasis of proteins, responsible for ensuring protein turnover, is regulated by proteases, which also participate in the etiopathogenesis of multiple conditions. The magic of proteases is such that, in blood coagulation, one same molecule, such as coagulation factor V, for example, can perform both a procoagulant and an anticoagulant function as a result of the activity of proteases. However, this magic has an insidious side to it, as it may also prevent the completion of the clinical value chain of factor V deficiency. This value chain encompasses the discovery of knowledge, the transfer of this knowledge, and its translation to clinical practice. In the case of rare and ultra-rare diseases like factor V deficiency, this value chain has not been completed as the knowledge acquisition phase has dragged out over time, holding up the transfer of knowledge to clinical practice. The reason for this is related to the small number of patients afflicted with these conditions. As a result, new indications must be found to make the therapies cost-effective. In the case of factor V, significant research efforts have been directed at developing a recombinant factor V capable of resisting the action of the proteases capable of inactivating this factor. This is where bioethics and health equity considerations come into the equation.

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“…The thrombin generation (TG) test is a global coagulation assay (1). An increased TG has been associated with thrombosis (2-4), whereas a decreased TG can result in bleeding episodes (5)(6)(7)(8)(9). This collection of articles illustrates the recent clinical and technical advances that have been made in the field of thrombin generation.…”

Section: Editorial On the Research Topic Advances In Thrombin Generationmentioning

confidence: 99%

Editorial: Advances in thrombin generation

Laat-Kremers

Zuily

Laat

2023

Front. Cardiovasc. Med.

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In patients with hemophilia, a decreased thrombin generation profile is associated with a severe bleeding phenotype

Cited by 10 publications

References 28 publications

Pattern of use and clinical outcomes with rIX‐FP in pediatric/adolescent patients with haemophilia B in Italy: Results from IDEAL real‐world study

Pattern of use and clinical outcomes with rIX‐FP in pediatric/adolescent patients with haemophilia B in Italy: Results from IDEAL real‐world study

The Magic of Proteases: From a Procoagulant and Anticoagulant Factor V to an Equitable Treatment of Its Inherited Deficiency

Editorial: Advances in thrombin generation

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