PURPOSE: The high mutational heterogeneity of hemophilia A is a challenge for provision of genetic services. Our aim was to create a confidential national database of mutations for improvement of genetic services in Slovenia. The factor VIII gene (F8) was analyzed in 150 of 179 hemophilia A patients in Slovenia. METHODS: The mutations were identified by testing inversions of intron 22 and 1 (IV22 and IV1) and sequencing part of the promoter, whole coding region and exon/intron boundaries of the F8 gene. There are 126 families with 179 patients with hemophilia A in Slovene registry for Hemophilia. RESULTS: We determined the mutations in 81/82 patients with severe, 15/18 with moderate and 54/79 with mild form of hemophilia A, representing approximately 80% of the families (100/126) in the Slovene registry for Hemophilia. Genetic mutation was determined in all analyzed patients: 40/150 have inversion of intron 22 (48,8% of severe cases) and another 110/150 have 54 different mutations in F8 gene which cause hemophilia A. Of these, 21 are so far found only among Slovene patients. Inversion of intron 1 was not detected in Slovene population of hemophilia A patients. 30% of the small deletions and insertions occurred at stretch of adenines in codons 1191-1194 (8As). In one patient with mild phenotype missense mutation in 5’UTR creating novel translation initiation site was found. CONCLUSION: The spectrum of mutations in Slovenian hemophilia A patients was comparable to that found in the Italian and Austrian population as expected. We report a wide spectrum of mutations in the national database. The type of mutation is one of the predictors of clinical phenotype. The database is a powerful tool for genetic counseling and medical care of families with hemophilia A in Slovenia.
F.02 Acquisition of new scientific knowledge
COBISS.SI-ID: 583852Umbilical cord blood (UCB) is an abundant source of haematopoietic stem cells (HSC) for allogeneic HSC transplant. Since the first UCB transplant in 1988, many scientific data have been collected. Many umbilical cord blood banks havebeen established worldwide for the collection and cryopreservation as wellas for the international exchange with more than 400,000 UC units available. There is probably a twofold figure of UCB units collected for the private UCB banks. More than 20,000 UCB units have been used for treating malignant and non-malignant diseases both in adults and children. Unrelated UCB HSCs became an alternative to bone-marrow derived HSCs based on their advantages, including a prompt availability, decrease of graftversus- host disease (GVHD) and better longterm immune recovery, resulting in a similar long-term survival. UCB stem cells can be transplanted to an allogeneic patient in spite of the high degree of HLA mismatches, which is highly important for the patients who cannot find a HLA-identical allogeneic donor. Since the low number of cells in the UCB units still represents the main causeof failure of engraftment, new strategies, such as double-unit UCB transplantation, intra-bone injection of UCB cells, simultaneous transplantation of accessory cells and the reduced intensity conditioning regimen, were developed to increase the success of UCB transplantation. Several clinical studies using UCB stem cells that have been previously expanded in vitro are underway. These procedures and the future development ofregenerative medicine will further broaden possible indications for the use of UCB derived stem cells in adults.
F.11 Development of a new service
COBISS.SI-ID: 29901785Background: Intracranial haemorrhage (ICH) is a serious complication of haemophilia that affects 3.5-4 % of all boys with haemophilia during the neonatal period. It is a leading cause of mortality and morbidity in neonates with haemophilia. Patients and Methods: The authors are presenting a case of aneonate with severe haemophilia A, who suffered postnatal ICH. They discuss dilemmas regarding the optimal mode and management of delivery in haemophilia carriers, the role of imaging techniques in diagnosing ICH and postpartum prophylaxis. Authors also discuss the choice of factor concentrate for the treatment of ICH and present the data on perinatal complications in neonates with severe haemophilia A in Slovenia in the period 1980-2010. Conclusions: ICH is a leading cause of mortality and morbidity in neonates with coagulationdisorders. Early recognition of ICH and early appropriate management are extremely important.
F.02 Acquisition of new scientific knowledge
COBISS.SI-ID: 29896665