Abstract Number: OC 49.1
Meeting: ISTH 2021 Congress
Background: Today, one of the main comorbidities affecting the quality of life of the haemophilic patient is bone pathology. The pathophysiology of the reduced bone mineral density (BMD) associated with haemophilia A is not exactly known and both processes of bone resorption and bone formation could be hypothesized to be altered. FVIII deficiency could alter BMD directly affecting bone cells or indirectly by decreasing thrombin generation.
Aims: This study aims to evaluate the role played by FVIII, von Willebrand Factor (VWF) and thrombin on both osteoclasts and osteoblasts biology.
Methods: In vitro assays assessed the osteoclastogenic potential of PBMC (Peripheral Blood Mononuclear Cells) isolated from a haemophilic patient. Osteoclastogenesis (differentiation and genes expression of DC-STAMP, MFR and RANK) and osteoclasts proteases (cathepsinK and MMP-9) activity were assessed in the presence of plasma derived VWF/FVIII complex, human rVWF, human full length rFVIII and thrombin. Osteoblasts differentiation, mineralization and genes expression (Alkaline Phosphatase and COL1A2) were performed in the presence of aforementioned coagulation factors.
Results: PBMC from HA patient showed increased ability to form mature osteoclasts compared to those obtained from healthy controls. Moreover, RNA expression analysis performed on patient’s osteoclasts revealed higher levels of RANK, TRAF6, CATHEPSIN K and TCIRG1 genes expression compared to control osteoclasts. VWF appears to play a major role, showing by itself ~45% inhibition of osteoclastogenesis comparable to OPG, and even more if is complexed with FVIII (53% inhibition). Thrombin reduces osteoclast differentiation with variable effects (30-50% inhibition).
No alteration of alkaline phosphatase positivity was observed in control osteoblasts treated with Thb and VWF, whereas incubation with FVIII leads to a statistically significant reduction, also revealed in osteoblasts treated with FVIII/VWF.
Conclusions: All these data support that bone loss observed in haemophilic patients could be related to increased osteoclast formation and activity and that coagulation factors directly impact on bone cells.
To cite this abstract in AMA style:Lancellotti S, Battafarano G, Sacco M, Tardugno M, Di Gennaro L, De Cristofaro R, Del Fattore A. Bone Disease in Hemophilia: The Role of Different Bone Cells [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/bone-disease-in-hemophilia-the-role-of-different-bone-cells/. Accessed January 23, 2022.
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