Abstract Number: PB0882
Meeting: ISTH 2021 Congress
Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » Platelet Antagonists and Novel Therapeutics
Background: GPIIb/IIIa inhibitors block platelet fibrinogen and vWF receptors thereby reducing clotting. In an emergency, these agents must be overcome to stop bleeding.
Aims: The aim of this study was to determine if Thrombosomes®, a lyophilized human platelet (LHP) hemostatic agent under clinical development, were resistant to the effect of GPIIb/IIIa antagonists and therefore restore hemostasis associated with GPIIb/IIIa antagonist mediated bleeding.
Methods: GPIIb/IIIa inhibitors representative of different classes of therapeutic molecules, an antibody (AP-2), a cyclic heptapeptide (eptifibatide) and a non-peptide small molecule (tirofiban) were tested for their ability to inhibit aggregation of donor and platelet rich plasma (PRP). Doses of each drug shown to inhibit aggregation of platelets were used to treat PRP and inhibit thrombus formation on the T-TAS® flow system over thromboplastin-collagen coated microcapillaries. Single donor platelets (standard of care for drug reversal) and LHP were compared for their ability to recover loss of occlusion in the presence of each drug.
Results: Unlike fresh platelets, LHP were shown to be non-responsive to ADP by aggregometry. At therapeutic doses, each drug was shown to inhibit ADP stimulated PRP aggregation. T‑TAS® occlusion time of PRP was approximately 15 minutes and increased to 25-30 minutes with drug treatment. Conversely, each inhibitor had no effect on the occlusion time of LHP of 15 minutes. When PRP treated with each GPIIb/IIIa inhibitors was dosed with LHP, occlusion times returned to normal (11-14 minutes). Dosing with equal number of single donor platelets did not recover normal occlusion.
Conclusions: LHP, unlike normal platelets, were resistant to GPIIb/IIIa antagonists. In vitro studies reveal that LHP can be used to recover the anti-thrombotic effect of GPIIb/IIIa inhibitors, potentially allowing continued drug compliance during procedures and as a possible treatment for bleeding while on GPIIb/IIIa antagonist therapy.
To cite this abstract in AMA style:
Dickerson M, Moskowitz K. Lyophilized Human Platelets Support Thrombosis Unlike Normal Platelets in the Presence of GPIIb/IIIa Antagonists [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/lyophilized-human-platelets-support-thrombosis-unlike-normal-platelets-in-the-presence-of-gpiib-iiia-antagonists/. Accessed December 7, 2021.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/lyophilized-human-platelets-support-thrombosis-unlike-normal-platelets-in-the-presence-of-gpiib-iiia-antagonists/