Bleeding is increased in amyloid precursor protein knockout mouse

Research and Practice in Thrombosis and Haemostasis
Nima MazinaniChristian J Kastrup

Abstract

Amyloid precursor protein (APP) is highly expressed in platelets. APP is the precursor to amyloid beta (Aβ) peptides that accumulate in cerebral amyloid angiopathy and plaques in Alzheimer disease. APP and its metabolites interact with many components of the coagulation system, and have both anticoagulant and procoagulant properties, but it is unclear if APP contributes to hemostasis in vivo. To determine whether APP contributes to hemostasis in mice, including when inhibitors of coagulation are administered. Blood loss in APP knockout (KO) mice was measured in liver laceration and tail transection models of hemorrhage. Blood loss was also measured following tail transection in mice given an inhibitor of coagulation factor Xa (apixaban), platelet inhibitors (aspirin + clopidogrel), tissue-type plasminogen activator (t-PA), or the antifibrinolytic tranexamic acid (TXA). Blood loss from liver lacerations was similar between APP KO mice and wild-type (WT) mice, but APP KO mice bled more from tail transections. When mice were challenged with aspirin + clopidogrel, the difference in bleeding between APP KO and WT mice was abrogated. In contrast, a difference in bleeding between the strains persisted when mice were treated with apixa...Continue Reading

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Citations

Nov 26, 2020·International Journal of Molecular Sciences·Benedetta IzziAlessandro Gialluisi

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