Boosting the coagulation restores haemostasis in ticagrelor-treated mice.
Blood Coagul Fibrinolysis
; 27(8): 913-919, 2016 Dec.
Article
em En
| MEDLINE
| ID: mdl-26757017
ABSTRACT
Antiplatelet therapy is given to patients with acute coronary syndrome to reduce the risk for thrombotic events, but may increase the risk for bleeding. Ticagrelor was administered intravenously to mice. Cumulative blood loss and bleeding time were measured after cutting 5âmm of the tail, 20âmin after the start of ticagrelor infusion. The tail was placed in a hemoglobin-sensitive device measuring light absorbance (abs) over time for 35âmin. Activated recombinant human factor VII (rhFVIIa; NovoSeven; NovoNordisk A/S, Bagsvaerd, Denmark) 1âmg/kg (study 1); recombinant human prothrombin (rhFII, MEDI8111) 10âmg/kg (study 2); or vehicle was given intravenously once bleeding had commenced, within 90s after tail cut. Ticagrelor resulted in more than 98% inhibition of ex-vivo ADP-induced platelet aggregation. In study 1, the median blood loss in the ticagrelor, vehicle, and rhFVIIa groups were 909, 122, and 397âabs*s, respectively (Pâ<â0.05 for both comparisons, including the ticagrelor group). Similar pattern was seen for bleeding time. The median bleeding time in the ticagrelor, vehicle, and rhFVIIa groups were 2003, 449, and 884s, respectively (Pâ<â0.05 for both comparisons, including the ticagrelor group). In study 2, the median blood loss and bleeding time in the ticagrelor group were 362âabs*s and 1847s. The corresponding numbers for the vehicle and rhFII groups were 71âabs*s and 613s, and 178âabs*s and 701s, respectively (Pâ<â0.05 for comparisons between ticagrelor and vehicle for both blood loss and bleeding time). In mice dosed to complete P2Y12 inhibition, boosting coagulation by administration of rhFVIIa or rhFII within 90s after bleeding initiation can partly reverse ticagrelor-enhanced bleeding.
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Base de dados:
MEDLINE
Assunto principal:
Coagulação Sanguínea
/
Adenosina
/
Antagonistas do Receptor Purinérgico P2Y
/
Hemostasia
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article