Abstract Number: PB0878
Meeting: ISTH 2022 Congress
Background: Anti-thrombotic medications carry an inherent risk of bleeding, which may be exacerbated when anti-coagulant and anti-platelet therapeutics are combined. Our lab has previously shown differences in the effects of anti-platelet versus anti-coagulant drugs on the structure and function of hemostatic plugs.
Aims: We examined whether dual anti-thrombotic treatment consisting of combined anti-platelet and anti-coagulant therapeutics is different than either therapy alone on hemostatic plug structure and function.
Methods: Mice were treated with the P2Y12 antagonist clopidogrel and the Factor Xa inhibitor rivaroxaban across a range of doses, either alone or in combination. The hemostatic response was assessed using a mouse jugular vein puncture injury model. Platelet accumulation, activation, and fibrin deposition were evaluated with quantitative multiphoton fluorescence microscopy.
Results: Mice treated with clopidogrel alone had significantly impaired platelet accumulation at the site of injury along with prolonged bleeding times and failure to achieve hemostasis at the highest doses of clopidogrel used (10-25 mg/Kg, p < 0.05). Mice given rivaroxaban alone instead showed a dose-dependent reduction in fibrin deposition (p < 0.05 at 1 mg/Kg) with no impact on bleeding. Mice treated with both clopidogrel and rivaroxaban had platelet and fibrin accumulation that was similar to either drug given alone, however, dual anti-thrombotic therapy resulted in impaired hemostasis at doses that had no impact on bleeding when given in isolation.
Conclusion(s): Conclusion: Combined administration of anti-platelet and anti-coagulant therapeutics has a greater impact on hemostatic plug function than either drug alone. Our findings highlight how platelet and fibrin deposition are differentially impacted by the use of either anti-thrombotic therapy in isolation, resulting in increased bleeding in the setting of dual therapy. We speculate that this enhanced bleeding stems from the combined loss of both ADP- and thrombin-mediated platelet activation. Our findings may help clinicians better understand bleeding risk associated with dual anti-thrombotic therapy.
To cite this abstract in AMA style:Mansi C, Severa J, Marar T, Stalker T. The Impact of Dual Anti-platelet, Anti Coagulation Therapy on Hemostatic Plug Structure and Function [abstract]. https://abstracts.isth.org/abstract/the-impact-of-dual-anti-platelet-anti-coagulation-therapy-on-hemostatic-plug-structure-and-function/. Accessed February 27, 2024.
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