Abstract Number: PB0325
Meeting: ISTH 2021 Congress
Background: Thrombosomes ® are lyophilized human platelet derivatives (LHP) currently under Phase 2 clinical trial for use in non-compressible hemorrhage, a condition with high mortality. The mechanism(s) of action in vivo have yet to be elucidated. Using humanized VWF HA1 transgenic mice, which have been previously reported to support human but not mouse platelet mediated hemostasis and thrombosis, we characterized the ability of LHP to support these critical biological processes.
Aims: To determine whether LHP (i) require VWF to support interactions at sites of vascular injury, (ii) can mediate platelet accrual in vivo, and (iii) can mitigate bleeding in response to trauma-induced injury.
Methods: An intravital model of laser-induced arteriole injury was employed to assess the behavior of fluorescently labeled LHP and/or human and mouse platelets within the microcirculation of the cremaster muscle of VWF HA1 mutant and VWF KO animals. A standard tail bleeding assay was used to determine their hemostatic properties compared to freshly isolated human platelets.
Results: Intravital studies revealed that human platelets were able to form large thrombi in laser-injured arterioles of VWF HA1 mutant but not VWF KO mice (max thrombus size of 6,985±697 µm2vs 185±110 µm2, respectively; mean + SD; n=10). In contrast, LHP accumulated to a similar extent in damaged arterioles in either animal without forming occlusive thrombi (max thrombus size of 6,436±1,753 µm2vs 5,902±1,694 µm2, respectively; mean + SD; n=10; P=0.22). Of note, only surface adherent LHP in VWF HA1 mice could (i) recruit a significant number human platelets into the growing thrombus, and (ii) restore hemostasis in response to amputation of distal tail tip (bleeding times of 257±135 s vs >600s for PBS treated).
Conclusions: LHP can accumulate at sites of vascular injury independent of VWF and circulating platelets but require VWF to support effective hemostasis.
To cite this abstract in AMA style:Zhou H, Lee A, Moskowitz K, Diacovo T. Hemostatic and Thrombogenic Properties of Lyophilized Human Platelets [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/hemostatic-and-thrombogenic-properties-of-lyophilized-human-platelets/. Accessed August 9, 2022.
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