Koert Gooijer

79 Chapter 4 Introduction Osteogenesis Imperfecta (OI) is an inherited connective tissue disorder primarily characterized by susceptibility to fractures. The prevalence of OI has been reported as 6-7 per 100,000 1. OI is a clinically and genetic heterogeneous disorder. Clinically, OI consists of 5 types (OI types 1-5) 2; blue sclerae, dentinogenesis imperfecta, hearing loss, joint hypermobility and short stature can be present as secondary features 3. Most patients with OI have a dominant pathogenic variant in either the COL1A1 or COL1A2 gene, which encode collagen type I alpha 1 chain and collagen type I alpha 2 chain, respectively. Collagen type I is abundant in bones, ligaments and tendons and has a triple helix structure. Dominant pathogenic variants result in decreased and/or abnormal production of collagen type 1 4. It is well known that the phenotype is influenced by the gene involved, the specific position of the variant and the variant type 2. Easy bruising is commonly reported by OI patients. Earlier studies reported coagulation abnormalities: prolonged bleeding time, abnormal prothrombin consumption 5,6, abnormalities in platelet function 6, large platelets 7, decreased platelet retention and reduced factor VIII (FVIII) 8. To our knowledge this is the second largest study after that of Evensen et al (1984), which reported on 58 clinically diagnosed OI patients 8. In addition, six case studies reported an increased bleeding risk, without abnormal coagulation tests or further details being available. Five of these six casereports described a single patient and one reported on 20 infants aged between 1 and 6 months old 9–14. To our knowledge, no recent studies have been performed in OI patients to identify or exclude a haematological cause. The aim of this study was firstly to investigate whether a bleeding tendency is present and, secondly, to perform haematological studies to identify or exclude coagulation disorders. Methods Study design and population An observational cohort pilot study was undertaken in the Expert Centre for adults with Osteogenesis Imperfecta, Isala Hospital, Zwolle, The Netherlands. All new adult patients with a clinical diagnosis of OI who attended the centre from March 2018 until June 2018 were approached for the study

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