Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions.
Blood
; 124(26): 3991-5, 2014 Dec 18.
Article
em En
| MEDLINE
| ID: mdl-25305202
ABSTRACT
The oral Bruton's tyrosine kinase inhibitor, ibrutinib, has recently demonstrated high efficiency in patients with relapsed B-cell malignancies. Occurrence of bleeding events has been reported in a subgroup of ibrutinib-treated patients. We demonstrate that ibrutinib selectively inhibits platelet signaling and functions downstream of the collagen receptor glycoprotein VI and strongly affects firm platelet adhesion on von Willebrand factor (VWF) under arterial flow. A longitudinal study of 14 patients indicated a correlation between occurrence of bleeding events and decreased platelet aggregation in response to collagen in platelet-rich plasma and firm adhesion on VWF under arterial flow. The addition of 50% untreated platelets was sufficient to efficiently reverse the effects of ibrutinib, and platelet functions recovered after treatment interruption as physiological platelet renewal occurred. These data have important clinical implications and provide a basis for hemostasis management during ibrutinib treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Pirimidinas
/
Plaquetas
/
Fator de von Willebrand
/
Colágeno
Tipo de estudo:
Observational_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article