Abstract Number: PB0786
Meeting: ISTH 2022 Congress
Background: Dual antiplatelet therapy (DAPT; aspirin + P2Y12 inhibitor) is a safe treatment for secondary prevention of arterial thrombotic events. However, due to risk of major hemorrhage, patients with thrombocytopenia (TP) are typically excluded from major clinical trials and the appropriate use of DAPT in these patients remains unclear.
Aims: To investigate the impact of thrombocytopenia on bleeding in the setting of DAPT.
Methods: To study how TP alters bleeding risk associated with DAPT, we assessed hemostatic plug formation by intravital microscopy following laser injury to the murine saphenous vein. Mice were treated, or not, with DAPT (aspirin 20 mg/kg; clopidogrel 25 mg/kg) and platelet counts were adjusted to >200, 100-200, or < 100 x 10^9/L. Time to initial hemostasis, re-bleeding events, and platelet accumulation were monitored. 3D reconstructions of platelet plugs were rendered from spinning disk confocal Z-stacks.
Results: WT mice with normal platelet counts rapidly achieved hemostasis with robust platelet accumulation and no rebleeding. Reducing the platelet count did not significantly affect hemostasis time or platelet accumulation. In contrast, DAPT treatment did not affect initial hemostasis times but led to significantly more re-bleeding, and platelet accumulation was reduced. Interestingly, reducing the platelet count in DAPT-treated mice down to 100-200 x 10^9/L did not further impair hemostasis, although the total bleeding time trended toward being longer. Significant changes were only observed in DAPT-treated mice with platelet counts below 100 x 10^9/L. Intravital imaging revealed instability of the center of the platelet plug, and initial hemostasis was never achieved at many of the injury sites.
Conclusion(s): Conclusions: DAPT-associated bleeding was exacerbated by low platelet counts, mainly due to loss of platelet mass at the site of injury. These results suggest that DAPT treatment could further increase bleeding risk in patients with platelet counts below 100 x 10^9/L.
This study was supported by ASH and NBF
To cite this abstract in AMA style:Lee R, Ballard A, Rudran T, Kawano T, Mackman N, Stouffer G, Bergmeier W. Dual anti-platelet therapy-associated bleeding is exacerbated by platelet counts < 100 x 10^9/L in mice due to impaired initial hemostatic plug formation [abstract]. https://abstracts.isth.org/abstract/dual-anti-platelet-therapy-associated-bleeding-is-exacerbated-by-platelet-counts-100-x-109-l-in-mice-due-to-impaired-initial-hemostatic-plug-formation/. Accessed October 2, 2023.
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