Drug-induced thrombocytopenia: mechanisms and relevance in preclinical safety assessment
| Autor: | Scott P. Henry, Nianyu Li, Padma Kumar Narayanan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Drug Induced Thrombocytopenia business.industry 010501 environmental sciences Toxicology Bioinformatics 01 natural sciences 03 medical and health sciences 030104 developmental biology Drug development hemic and lymphatic diseases Medicine business 0105 earth and related environmental sciences |
| Zdroj: | Current Opinion in Toxicology. 17:23-30 |
| ISSN: | 2468-2020 |
| DOI: | 10.1016/j.cotox.2019.10.002 |
| Popis: | Thrombocytopenia is one of the most commonly observed drug-induced adverse hematologic toxicities in the clinic. Therefore, in vitro and in vivo evaluations of effect of drugs on platelets are an important component in preclinical safety assessment in drug development. To date, a number of mechanisms have been identified to be associated with drug-mediated thrombocytopenia. Amongst these, some are conserved across species whereas others are not. Therefore, a case-by-case approach is needed to assess drug-induced thrombocytopenia at preclinical stages to understand translatability to humans. The present chapter reviews mechanisms in drug-mediated thrombocytopenia with a focus on nonimmune (direct myelotoxicity) as well as immune-mediated thrombocytopenia by both small and large molecule therapeutics. Several in vitro and in vivo models as well as challenges in assessing drug-mediated thrombocytopenia in preclinical stages will also be discussed. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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