Abstract Number: OC 63.1
Meeting: ISTH 2022 Congress
Background: Heterogeneity in clinical bleeding phenotype is observed in hemophilia patients with similar factor VIII or factor IX activity levels. Thrombin generation (TG) as a global hemostasis assay may contribute to better predict which patients are at increased risk of bleeding.
Aims: To quantify the association between clinical bleeding phenotype and TG profile in hemophilia patients.
Methods: The Nijmegen Hemostasis Assay (NHA), which simultaneously measures TG and plasmin generation, was performed in 863 hemophilia patients (adults and children) originating from the sixth Hemophilia in the Netherlands study. Patients using prophylaxis underwent a washout period. Ethical approval and written informed consent were obtained. Severe clinical bleeding phenotype was defined as an annual bleeding rate (ABR) ≥5 or an annual joint bleeding rate (AJBR) ≥3. Correlations were determined using Spearman’s correlation test.
Results: TG parameters significantly differed between hemophilia patients and healthy controls (thrombin peak height (TPH) in severe 1.0nM [IQR 1.0-1.0], moderate 25.5nM [1.0-46.5], mild hemophilia A 47.4nM [27.9-71.1], and controls 266.5nM [252.8-280.6]; thrombin potential in severe 1.0nM·min [1.0-1.0], moderate 607.6nM·min [1.0-1083.0], mild hemophilia A 1034.0nM·min [668.4-1398.0], and controls 2088.0nM·min [1988.0-2175.0]). Weak but significant correlations were found between clinical bleeding phenotype and TPH (ABR r=-0.2571; AJBR r=-0.2776) or thrombin potential (ABR r=-0.2752; AJBR r=-0.3084) (Figure 1). A severe clinical bleeding phenotype was observed in patients with a TPH < 35% and a thrombin potential < 70%, independent of hemophilia severity. Median TPH and thrombin potential were significantly lower in patients with a severe clinical bleeding phenotype versus a mild clinical bleeding phenotype (TPH: 0.4% vs 17%; thrombin potential 0.05% vs 46%) (Figure 2).
Conclusion(s): A decreased TG profile is associated with severe clinical bleeding phenotype in hemophilia patients. TG parameters in combination with clinical bleeding severity may be better tools to personalize prophylactic replacement therapy, irrespective of hemophilia severity.
To cite this abstract in AMA style:Verhagen M, van Heerde W, van der Bom J, Beckers E, Blijlevens N, Coppens M, Gouw S, Jansen J, Leebeek F, van Vulpen L, Meijer D, Schols S. Decreased thrombin generation profile is associated with severe bleeding phenotype in hemophilia: data from the Hemophilia in the Netherlands study [abstract]. https://abstracts.isth.org/abstract/decreased-thrombin-generation-profile-is-associated-with-severe-bleeding-phenotype-in-hemophilia-data-from-the-hemophilia-in-the-netherlands-study/. Accessed October 1, 2023.
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