Mappings established between Knowledge Organization Systems (KOS) increase semantic interoperability between biomedical information systems. However, biomedical knowledge is highly dynamic and changes affecting KOS entities can potentially invalidate part or the totality of existing mappings. Understanding how mappings evolve and what the impacts of KOS evolution on mappings are is therefore crucial for the definition of an automatic approach to maintain mappings valid and up-to-date over time. In this article, we study variations of a specific KOS complex change (split) for two biomedical KOS (SNOMED CT and ICD-9-CM) through a rigorous method of investigation for identifying and refining complex changes, and for selecting representative cases. We empirically analyze and explain their influence on the evolution of associated mappings. Results point out the importance of considering various dimensions of the information described in KOS, like the semantic structure of concepts, the set of relevant information used to define the mappings and the change operations interfering with this set of information.