Abstract Number: PB1254
Meeting: ISTH 2022 Congress
Background: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal-dominant genetic disorder involving defects in two predominant genes known as endoglin (ENG; HHT-1) and activin receptor-like kinase 1 (ACVRL1/ALK1; HHT-2). It is characterized by mucocutaneous telangiectases that, due to their fragility, frequently break causing recurrent epistaxis and gastrointestinal bleeding. Because of the severity of hemorrhages, the study of the hemostasis involved in these vascular ruptures is critical to find therapies for this disease.
Aims: The aim of this study is to analyze the different processes involved in hemostasis in the most common genetic models of HHT, namely Eng+/- for HHT-1 and Alk1+/- for HHT-2
Methods: The analysis of the general process of hemostasis was performed by studying the bleeding time of the tail. Platelet activation and aggregation analyses were performed for the study of primary hemostasis, together with in vitro or in vivo platelet-endothelium interaction studies. Fibrinolysis was studied by studying serum levels of fibrinogen, tPA, PAI-1, and D-dimer.
Results: In Eng+/- mice, the results of in vivo and in vitro assays suggest deficient platelet-endothelium interactions that impair a robust and stable thrombus formation. Consequently, the thrombus could be torn off and dragged by the mechanical force exerted by the bloodstream, leading to the reappearance of hemorrhages (Figure 1A). In Alk1+/- mice, overactivation of the fibrinolysis system was observed (Figure 1B)
Conclusion(s): These results support the idea that endoglin and Alk1 haploinsufficiency leads to a common phenotype of impaired hemostasis, but through different mechanisms. This contribution opens new therapeutic approaches to HHT patients’ epistaxis.
To cite this abstract in AMA style:Egido-Turrion C, Rossi E, Ollauri-Ibáñez C, Pérez-García M, Sevilla M, Bastida J, González-Porras J, Rodríguez-Barbero A, Bernabeu C, Lopez-Novoa J, Pericacho M. Functional Alterations Involved In Increased Bleeding In Hereditary Hemorrhagic Telangiectasia Mouse Models [abstract]. https://abstracts.isth.org/abstract/functional-alterations-involved-in-increased-bleeding-in-hereditary-hemorrhagic-telangiectasia-mouse-models/. Accessed March 4, 2024.
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