Abstract Number: PB0377
Meeting: ISTH 2020 Congress
Background: Circulating microparticles (MPs) express phosphatidylserine, which provides a binding site for coagulation factors and cofactors. We have previously found that MPs improve thrombin generation and fibrin formation in hemophilia A (HA) plasma models in vitro.
Aims: To test the procoagulant effect of MPs in HA mice in vivo.
Methods: MPs isolated from pooled normal human plasma, either alone (3.8 × 104 MPs/g mice) or with recombinant FVIII (rFVIII, 5 or 25 IU/kg), were administered into HA mice intravenously. Following administration, a saphenous vein bleeding model was performed, and the bleeding parameters were recorded. After that, mice blood was collected, and tested using the whole blood thrombin generation and the overall hemostatic potential assays. The fibrin clot structure was analysed using scanning electron microscopy.
Results: The average bleeding time of HA mice were significantly shortened in mice treated with MPs compared to saline, while the number of hemostatic events tended to be higher. The bleeding phenotype was improved as expected after administration of rFVIII, however, the addition of MPs did not induce any further improvement. The thrombin generation, the overall coagulation potential and fibrin clot density were not improved after administration of MPs either alone or together with rFVIII.
Conclusions: It seems that administration of MPs improve the bleeding phenotype in HA mice, but does not enhance the procoagulant effect of rFVIII, suggesting that their mechanism of action may be different in vivo. Additionally, MPs cannot completely compensate for the FVIII deficiency. Mice treated with MPs did not show any improvement of the ex-vivo global hemostasis, suggesting that MPs might be either removed from the circulation in vivo or consumed due to incorporation during the formation of hemostatic plugs.
To cite this abstract in AMA style:Zong Y, Pruner I, Wan J, Ninivaggi M, Rasmuson A, Laat BD, Antovic J. Procoagulant Microparticles Improve Hemostasis in Mice with Haemophilia A [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/procoagulant-microparticles-improve-hemostasis-in-mice-with-haemophilia-a/. Accessed January 21, 2022.
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