Abstract Number: PB0992
Meeting: ISTH 2021 Congress
Background: A recent report (J Wang et al. Blood 2019; 134:645) showed that sphingomyelin (SM), an abundant phospholipid on the outer leaflet of cell membranes, inhibits the activation of TF in mouse monocytes. In fact, blockade of acidic sphingomyelinase (AsMase) by desipramine and imipramine attenuated the LPS-induced procoagulant activity of TF without affecting de novo synthesis of the protein. We have previously shown that human platelets synthesize and contain functional TF, which releases its activity after ristocetin-induced VWF(VWF-R)-GPIbα binding.
Aims: Now, we examine the effect of desipramine on human platelet procoagulant activity induced by VWR-R-GPIbα activation.
Methods: Control PRP platelets and PRP pre-incubated (30 min, 37°C) with 10μM desipramine were stimulated with Ristocetin or TRAP. We measured light transmission platelet aggregation, serotonin secretion and serotonin content (HPLC), P-selectin secretion and Annexin V binding (FC). The PCA was assessed with Factor Xa generation (fluorometric tenase assay) and thrombin generation in PRP without including TF in the reaction solutions (Thrombinoscope).
Results: Desipramine induced a significant decrease in phosphatidylserine (PS) expression (Annexin V binding) in VWF-R-activated platelets (mean±SD of 7.5±4.7 to 4.7±3.3 % of labeled platelets, p<0.03), but not in TRAP-stimulated platelets (5.4±5.5 to 4.8±3.7 % of labeled platelets, p:NS); however, this change was not accompanied with concomitant reductions of FXa and thrombin generation (Endogenous Thrombin Potential and Velocity Index). Similarly, desipramine induced no significant changes in platelet aggregation, secretion of serotonin and P-selectin and platelet serotonin content.
Conclusions: Desipramine, an inhibitor of ASMase, decreases PS exposure without affecting GPIbα-TF-FVIIa clotting pathway in human platelets, contrasting with the observations in mice macrophages. These initial findings suggest that PS translocation would not be determinant in triggering platelet TF-dependent PCA.
To cite this abstract in AMA style:Panes O, Becerra MF, Mezzano D. Desipramine Reduces the Exposure of Phosphatidylserine on the Surface of Human Platelets, but Does Not Inhibit Platelet TF-induced Procoagulant Activity [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/desipramine-reduces-the-exposure-of-phosphatidylserine-on-the-surface-of-human-platelets-but-does-not-inhibit-platelet-tf-induced-procoagulant-activity/. Accessed August 15, 2022.
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