Session: 322. Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Bleeding and Clotting, hemophilia, Diseases
Patients and Methods: Οne hundred sixty two children and adolescents (mean age: 11.7 years, range 1-18.5 years) with severe, moderate and mild (n= 8) hemophilia A or B (n=11), on prophylaxis or on demand treatment (n= 6) were included in the study. Of them, 69 patients with median age of 11 years had no signs of HA (NHAP), 70 patients with median age of 14 years had arthropathy (HAP), while 23 patients with median age of 15.5 years presented with acute bleeding -hemarthrosis or muscle bleed- at the time of the biomarkers’ measurement- (AB). In all patients along with standard care laboratory evaluation, measurements of plasma circulating levels of DKK-1, RANKL, OPG, SOST and OPN were performed using immunoenzymatic techniques. Data are presented as mean ± SEM.
Results: We found that a) DKK-1 levels were higher in patients with NHAP and AB compared to patients with HAP, 3.396.0±194.0 pg/mL and 3.221±282.2 pg/mL vs 2.544±172.7 pg/mL (p=0.002); b) SOST levels in patients with NHAP (192.5±27.0 pg/mL), HAP (205.5±22.3 pg/mL) and AB (188.9±30.3 pg/mL) did not differ between the groups of patients (p>0.950); c) OPG levels in patients with NHAP (9.6±0.2 pg/mL), HAP (9.3±0.3 pg/mL) and AB (8.5±0.3 pg/mL) and RANKL levels in patients with NHAP (673.0±53.9 pg/mL), HAP (717.6±53.0 pg/mL) and AB (728.0±75.0 pg/mL) did not differ between the groups of patients (p>0.148 and p>0.515, respectively); d) Similarly, OPN levels in patients with NHAP (57.6±6.9 pg/mL), HAP (65.2±7.3 pg/mL) and AB (59.4±5.9 pg/mL) did not differ between the groups of patients (p>0.822) and e) DKK-1 and OPG levels correlated significantly with FVIII/FIX levels at the time of measurement (r=-0.553, p=0.014 and r=-0.540, p=0.017, respectively).
Conclusions: In this study, no significant perturbations of the crucial pathways regulating bone remodeling such as Wnt/β-catenin and RANKL/OPG systems were identified, by measuring circulating levels of key proteins involved in these pathways. Circulating DKK-1 seems to be a more sensitive biomarker indicating a potential decrease in osteoblastic activity. It appears that bone loss is rather rare in well-treated children and adolescents with hemophilic arthropathy comparing to young patients without arthropathy. Further studies are needed in order to determine how biomarkers in serum could play a prognostic role in the evolution of arthropathy from an early age in children and adolescents with hemophilia A or B, as well as the role of FVIII and FIX in bone metabolism, with the aim to ameliorate treatment strategies and prevent joint damage.
Disclosures: No relevant conflicts of interest to declare.
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