Abstract Number: PB0708
Meeting: ISTH 2020 Congress
Background: Neonatal hypoxic-ischemic encephalopathy is one of the primary causes of severe injury among newborns. Nowadays, no effective treatment is available. Estrogens (estradiol (E2) and estetrol (E4)) play an important role in the brain development and protection. New injectable liposomes encapsulating E2 or E4 were developed in order to enhance its crossing through the blood-brain barrier and limit systemic hormone-receptor interactions. The impact of such new formulations on platelet aggregation, coagulation and endothelial cells is not known.
Aims: To assess the hemocompatibility including platelet aggregation, coagulation and endothelial cells of new injectable liposomes encapsulating E2 or E4.
Methods: The impact of E2 and E4, alone or encapsulated into liposomes on the coagulation has been assessed using the calibrated automated thrombogram using normal pool plasma. Platelet aggregation analyses were performed with optical aggregometry using different inducers (adenosine diphosphate, arachidonic acid and collagen) on platelet-rich plasma. Viability and mortality assays were performed on endothelial cell lines (EAhy926) exposed during 24 hours to E2 and E4, alone or encapsulated into liposomes at doses ranging from 1ng/ml to 100µg/ml.
Results: No toxicity was observed on endothelial cells, coagulation and platelet aggregation with liposomes encapsulating E4 and E4 alone. For liposomes encapsulating E2, an antiaggregating effect is observed when collagen is used as inducer while E2 alone had no impact on platelets. E2 encapsulated in liposomes and E2 alone had not effect on coagulation. On endothelial cells, E2 alone induced a decrease of cell viability from 10µg/ml while encapsulated E2 has not.
Conclusions: Estetrol (E4) alone or encapsulated has no effects on platelet aggregation and thrombin generation and on endothelial cells confirming the hemocompatibility of this formulations for intravenous administration. The use of injectable liposome formulations encapsulating E4 is a promising strategy in newborns at risk of neonatal hypoxic-ischemic encephalopathy.
To cite this abstract in AMA style:Laloy J, Palazzo C, Delvigne A-, Piel G, Douxfils J, Foidart J-, Dogné J-. Blood Compatibility of Injectables Liposomes Encapsulating Estrogen Estetrol to Prevent Cerebral Ischemia of Prematurity [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/blood-compatibility-of-injectables-liposomes-encapsulating-estrogen-estetrol-to-prevent-cerebral-ischemia-of-prematurity/. Accessed May 18, 2021.
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